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認知症

著者: 柴﨑俊一 ひたちなか総合病院 救急・総合内科

監修: 山中克郎 福島県立医科大学会津医療センター総合内科

著者校正済:2021/03/24
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. DSM-5やICD-10の認知症の診断基準には「せん妄がないこと」と記されており、感度の高い(94%)錯乱評価法も用いてせん妄を除外することは強く推奨される(推奨度1)
  1. 認知症の診断基準として、感度97%、κ値0.81のDSM-R(DSM-)、あるいは同等の信頼性のあるICD-10を利用することは強く推奨される(推奨度1)DSM-5の認知症の診断基準では「認知機能の低下が他の精神疾患で説明できないこと」とされており、積極的にうつ病や統合失調症らしくないことを確認することが強く推奨される(推奨度1)
  1. MMSEは簡易スクリーニング検査でありながら感度84%、特異度87%と優れた検査特性を持ち、認知症を疑う患者には強く推奨される(推奨度1)
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  1. 血算は一般的な検査項目であり、認知症の原因となり得るか、認知症に影響を与えるであろうビタミンB12欠乏、葉酸欠乏を疑うきっかけとなる貧血、大赤血球症を検索するのに有用であるため、推奨される(推奨度2)。
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  1. ビタミンB12欠乏患者の認知機能は非欠乏者よりもやや低く、ビタミンB12欠乏自体は高齢者では頻度が高いため、ビタミンB12の測定はすべての認知症患者で推奨される(推奨度2)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
柴﨑俊一 : 特に申告事項無し[2021年]
監修:山中克郎 : 未申告[2021年]

改訂のポイント:
  1. 定期レビューを行い、診断法や治療法について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 認知症の有病率はわが国では65歳以上で約15%、平成24年人口からの推計では462万人と推定されている[1]
  1. 厚生労働省の試算では、日常生活自立度Ⅱ(日常生活に支障をきたすような症状・行動や意思疎通の困難さが多少見られても、誰かが注意していれば自立できる)以上のわが国の認知症高齢者は2010年で280万人、2020年で410万人、2025年で470万人とされている[2]
  1. 一方で、米国を中心に先進国では徐々に認知症の有病割合が減ってきているとの報告があり、日本でも有病割合が変化していくことが予想される[3]
  1. 高齢患者の認知症のほとんどはアルツハイマー病(約70%)。次いで血管性認知症(10%)、レビー小体型認知症(5%)。
  1. 近年、認知症の原因となる神経核内封入体病の報告が増えているが、正確な有病割合は不明である。
  1. 潜在的に可逆性の認知症は9%と頻度は少ないが、その可逆性は早期の発見・治療に懸かっている。また若年者や短期間の認知症患者では多い。
  1. 認知症の原因とはならず、それゆえに認識されない内科的疾患は、認知症の患者には多く、これらの疾患の治療は、ある程度認知機能を改善し得る。
 
  1. 可逆性認知症の頻度は少ないが、その可逆性は早期の発見・治療に懸かっていることから、見逃さない姿勢が強く推奨される(推奨度1)。認知症に影響する内科疾患の把握やアルツハイマー病の診断のためにも、全身の評価が必要である。
  1. メタアナリシスにて潜在的に可逆性の認知症(potentially reversible dementia、PRD)の割合は9%、介入によって実際に改善したものは0.6%だけであった[4]
  1. しかし、107例の前向きコホート研究(C)[5]では、PRDは有意に軽症であり、可逆性は認知機能低下の重症度と逆相関すると考えると、早期発見・早期治療が重要と考えられる。
  1. また同研究[5]では、15例のPRDのうち3例で完全に、8例で部分的に認知症の改善を認めた。
  1. 一方で、認知症の直接の原因とはならないが認知症を増悪させ得る未診断の内科疾患が48例で存在する。
  1. これらの治療により、14例で認知症の改善およびADLの上昇を認めており、幅広い全身評価の必要性がうたわれている。
  1. またアルツハイマー病の診断のためにもPRDの除外は必要である。
問診・診察のポイント  
  1. ①病歴聴取、身体所見、神経所見、②スクリーニング検査、③選択的な検査――の3つのステップがある。
  1. 認知症診断の約9割が病歴聴取、身体所見、精神状態の評価を含めた神経所見によって行われる。家族・知人からの情報も重要である。

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文献 

著者: Kenneth M Langa, Eric B Larson, Eileen M Crimmins, Jessica D Faul, Deborah A Levine, Mohammed U Kabeto, David R Weir
雑誌名: JAMA Intern Med. 2017 Jan 1;177(1):51-58. doi: 10.1001/jamainternmed.2016.6807.
Abstract/Text Importance: The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the United States and other high-income countries suggest that the age-specific risk of dementia may have declined over the past 25 years. Clarifying current and future population trends in dementia prevalence and risk has important implications for patients, families, and government programs.
Objective: To compare the prevalence of dementia in the United States in 2000 and 2012.
Design, Setting, and Participants: We used data from the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal survey of individuals in the United States 65 years or older from the 2000 (n = 10 546) and 2012 (n = 10 511) waves of the HRS.
Main Outcomes and Measures: Dementia was identified in each year using HRS cognitive measures and validated methods for classifying self-respondents, as well as those represented by a proxy. Logistic regression was used to identify socioeconomic and health variables associated with change in dementia prevalence between 2000 and 2012.
Results: The study cohorts had an average age of 75.0 years (95% CI, 74.8-75.2 years) in 2000 and 74.8 years (95% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4% (95% CI, 57.3%-59.4%) of the 2000 cohort was female compared with 56.3% (95% CI, 55.5%-57.0%) of the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older decreased from 11.6% (95% CI, 10.7%-12.7%) in 2000 to 8.8% (95% CI, 8.2%-9.4%) (8.6% with age- and sex-standardization) in 2012 (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.8 years [95% CI, 11.6-11.9 years] to 12.7 years [95% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile (eg, prevalence of hypertension, diabetes, and obesity) among older US adults.
Conclusions and Relevance: The prevalence of dementia in the United States declined significantly between 2000 and 2012. An increase in educational attainment was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain. Continued monitoring of trends in dementia incidence and prevalence will be important for better gauging the full future societal impact of dementia as the number of older adults increases in the decades ahead.

PMID 27893041  JAMA Intern Med. 2017 Jan 1;177(1):51-58. doi: 10.1001/・・・
著者: A Mark Clarfield
雑誌名: Arch Intern Med. 2003 Oct 13;163(18):2219-29. doi: 10.1001/archinte.163.18.2219.
Abstract/Text BACKGROUND: In 1988, 2 meta-analyses suggested that the prevalence of reversible dementia was significantly lower than had been previously estimated. It was predicted that further work would indicate an even lower rate. The present study represents an updated meta-analysis of the true prevalence of reversible dementia.
METHODS: MEDLINE was searched from 1987 through 2002. References were also gleaned from pertinent articles and relevant textbooks. Data were extracted on the nature and provenance of the studies, dementia etiology, and the proportion of cases that were potentially reversible and reversed.
RESULTS: Fifty articles were identified of which 39 met the study criteria, representing 7042 patients of whom 5620 (87.2%) had dementia. Patients were classified according to etiology and, where possible (in 23 [59%] of 39 studies), whether the dementia partially or completely resolved. A much higher proportion of studies than was previously the case were either community-based (31%) or observed subjects from outpatient departments (54%). Alzheimer disease was still the commonest cause of dementia (56.3%) followed by a vascular etiology (20.3%). Conditions requiring neuroimaging made up only 2.2% of cases. Potentially reversible causes were seen in 9%, and only 0.6% of dementia cases actually reversed (0.29% partially, 0.31% fully).
CONCLUSIONS: The reported proportion of dementias that reverse is much lower than previously thought. While comorbidity should always be treated for its own sake and in the hope that cognitive decline may at least be delayed, the present findings have significant clinical and economic implications for the workup of dementia.

PMID 14557220  Arch Intern Med. 2003 Oct 13;163(18):2219-29. doi: 10.1・・・
著者: E B Larson, B V Reifler, H J Featherstone, D R English
雑誌名: Ann Intern Med. 1984 Mar;100(3):417-23.
Abstract/Text We prospectively studied the evaluation of dementia in 107 unselected outpatients; 83 had so-called "irreversible" dementias, including 74 who had an Alzheimer-type dementia. Fifteen patients had potentially reversible dementias, of which hypothyroidism and drug toxicity were the commonest causes. Distinguishing features of reversible dementia were shorter duration, use of more prescription drugs, and less severe dementia. Almost half of the patients had other previously unrecognized treatable medical diseases. Most diagnoses were made from patient history and physical and mental status examination. Patients with reversible dementia improved but rarely reverted to normal. Objective improvement occurred in 25 patients after treating unrecognized coexistent medical and psychiatric diseases, or stopping unnecessary medication. Careful clinical observation is the most useful part of the evaluation and extensive testing may not be required for all patients. Overemphasis on distinguishing reversible from irreversible forms of dementia may detract from recognition of commoner, treatable causes of dysfunction and suffering.

PMID 6696360  Ann Intern Med. 1984 Mar;100(3):417-23.
著者: Malaz Boustani, Britt Peterson, Laura Hanson, Russell Harris, Kathleen N Lohr, U.S. Preventive Services Task Force
雑誌名: Ann Intern Med. 2003 Jun 3;138(11):927-37. doi: 10.7326/0003-4819-138-11-200306030-00015.
Abstract/Text BACKGROUND: Dementia is a large and growing problem but is often not diagnosed in its earlier stages. Screening and earlier treatment could reduce the burden of suffering of this syndrome.
PURPOSE: To review the evidence of benefits and harms of screening for and earlier treatment of dementia.
DATA SOURCES: MEDLINE, PsycINFO, EMBASE, the Cochrane Library, experts, and bibliographies of reviews.
STUDY SELECTION: The authors developed eight key questions representing a logical chain between screening and improved health outcomes, along with eligibility criteria for admissible evidence for each question. Admissible evidence was obtained by searching the data sources.
DATA EXTRACTION: Two reviewers abstracted relevant information using standardized abstraction forms and graded article quality according to U.S. Preventive Services Task Force criteria.
DATA SYNTHESIS: No randomized, controlled trial of screening for dementia has been completed. Brief screening tools can detect some persons with early dementia (positive predictive value < or =50%). Six to 12 months of treatment with cholinesterase inhibitors modestly slows the decline of cognitive and global clinical change scores in some patients with mild to moderate Alzheimer disease. Function is minimally affected, and fewer than 20% of patients stop taking cholinesterase inhibitors because of side effects. Only limited evidence indicates that any other pharmacologic or nonpharmacologic intervention slows decline in persons with early dementia. Although intensive multicomponent caregiver interventions may delay nursing home placement of patients who have caregivers, the relevance of this finding for persons who do not yet have caregivers is uncertain. Other potential benefits and harms of screening have not been studied.
CONCLUSIONS: Screening tests can detect undiagnosed dementia. In persons with mild to moderate clinically detected Alzheimer disease, cholinesterase inhibitors are somewhat effective in slowing cognitive decline. The effect of cholinesterase inhibitors or other treatments on persons with dementia detected by screening is uncertain.

PMID 12779304  Ann Intern Med. 2003 Jun 3;138(11):927-37. doi: 10.7326・・・
著者: B Brent Simmons, Brett Hartmann, Daniel Dejoseph
雑誌名: Am Fam Physician. 2011 Oct 15;84(8):895-902.
Abstract/Text As the proportion of persons in the United States older than 65 years increases, the prevalence of dementia will increase as well. Risk factors for dementia include age, family history of dementia, apolipoprotein E4 genotype, cardiovascular comorbidities, chronic anticholinergic use, and lower educational level. Patient history, physical examination, functional assessment, cognitive testing, laboratory studies, and imaging studies are used to assess a patient with suspected dementia. A two-visit approach is time-effective for primary care physicians in a busy outpatient setting. During the first visit, the physician should administer a screening test such as the verbal fluency test, the Mini-Cognitive Assessment Instrument, or the Sweet 16. These tests have high sensitivity and specificity for detecting dementia, and can be completed in as little as 60 seconds. If the screening test result is abnormal or clinical suspicion of another disease is present, appropriate laboratory and imaging tests should be ordered, and the patient should return for additional cognitive testing. A second visit should include a Mini-Mental State Examination, Geriatric Depression Scale, and verbal fluency and clock drawing tests, if not previously completed.

PMID 22010769  Am Fam Physician. 2011 Oct 15;84(8):895-902.
著者: Christopher M Callahan, Frederick W Unverzagt, Siu L Hui, Anthony J Perkins, Hugh C Hendrie
雑誌名: Med Care. 2002 Sep;40(9):771-81. doi: 10.1097/01.MLR.0000024610.33213.C8.
Abstract/Text OBJECTIVE: To design a brief cognitive screener with acceptable sensitivity and specificity for identifying subjects with cognitive impairment.
DESIGN: Cohort one is assembled from a community-based survey coupled with a second-stage diagnostic evaluation using formal diagnostic criteria for dementia. Cohort two is assembled from referrals to a specialty clinic for dementing disorders that completed the same diagnostic evaluation.
SETTING: Urban neighborhoods in Indianapolis, Indiana and the Indiana Alzheimer Disease Center.
PATIENTS: Cohort one consists of 344 community-dwelling black persons identified from a random sample of 2212 black persons aged 65 and older residing in Indianapolis; cohort two consists of 651 subject referrals to the Alzheimer Disease Center.
MEASUREMENTS: Formal diagnostic clinical assessments for dementia including scores on the Mini-mental state examination (MMSE), a six-item screener derived from the MMSE, the Blessed Dementia Rating Scale (BDRS), and the Word List Recall. Based on clinical evaluations, subjects were categorized as no cognitive impairment, cognitive impairment-not demented, or demented.
RESULTS: The mean age of the community-based sample was 74.4 years, 59.4% of the sample were women, and the mean years of education was 10.1. The prevalence of dementia in this sample was 4.3% and the prevalence of cognitive impairment was 24.6%. Using a cut-off of three or more errors, the sensitivity and specificity of the six-item screener for a diagnosis of dementia was 88.7 and 88.0, respectively. In the same sample, the corresponding sensitivity and specificity for the MMSE using a cut-off score of 23 was 95.2 and 86.7. The performance of the two scales was comparable across the two populations studied and using either cognitive impairment or dementia as the gold standard. An increasing number of errors on the six-item screener is highly correlated with poorer scores on longer measures of cognitive impairment.
CONCLUSIONS: The six-item screener is a brief and reliable instrument for identifying subjects with cognitive impairment and its diagnostic properties are comparable to the full MMSE. It can be administered by telephone or face-to-face interview and is easily scored by a simple summation of errors.

PMID 12218768  Med Care. 2002 Sep;40(9):771-81. doi: 10.1097/01.MLR.00・・・
著者: J R Hodges, C P Warlow
雑誌名: J Neurol Neurosurg Psychiatry. 1990 Oct;53(10):834-43.
Abstract/Text Of 153 patients presenting with acute transient amnesia, 114 fulfilled the proposed strict diagnostic criteria for transient global amnesia (TGA). The prognosis of this group was excellent with the exception of a small subgroup (7%), largely identifiable because of atypically brief or recurrent attacks, who developed epilepsy of temporal lobe type on follow up. Computerised tomography (CT) scans performed on 95 patients were normal, evidence for covert alcoholism was lacking and there was a familial incidence of approximately 2%. By contrast, the group of 39 patients who did not meet the criteria for TGA had a significantly worse prognosis with a high incidence of major vascular events. The groups could not be distinguished on the basis of behavioural characteristics during the attack. The following classification was proposed: 1) pure TGA--attacks fulfilling the strict criteria, and of more than one hour in duration which do not require detailed investigation, 2) probable epileptic amnesia--attacks of less than an hour or rapidly recurrent, 3) probable transient ischaemic amnesia, a minority of cases with additional focal neurological deficits during the attack.

PMID 2266362  J Neurol Neurosurg Psychiatry. 1990 Oct;53(10):834-43.
著者: Christopher R Butler, Kim S Graham, John R Hodges, Narinder Kapur, Joanna M Wardlaw, Adam Z J Zeman
雑誌名: Ann Neurol. 2007 Jun;61(6):587-98. doi: 10.1002/ana.21111.
Abstract/Text OBJECTIVE: Transient amnesia can be the principal manifestation of epilepsy. This diagnosis, however, is seldom suspected by clinicians and remains controversial. The amnestic attacks are often associated with persistent memory complaints. This study was designed to provide the first description of transient epileptic amnesia in a substantial series of patients.
METHODS: Fifty patients were recruited over 18 months using the following diagnostic criteria: (1) recurrent, witnessed episodes of amnesia; (2) other cognitive functions intact during attacks; and (3) compelling evidence of epilepsy. We assessed clinical features and performed neuropsychological evaluation in cases and 24 matched control subjects.
RESULTS: Transient epileptic amnesia develops in later life (mean onset, 62 years). Amnestic episodes are frequent (median, 12/year), brief (median duration, 30-60 minutes), and often occur on waking (37/50 cases). Epilepsy was the initial specialist diagnosis in only 12 of 50 cases. Attacks ceased on anticonvulsant medication in 44 of 47 treated patients. A total of 40 of 50 cases described persistent memory difficulties. Despite normal performance on standard memory tests, patients exhibited accelerated forgetting of verbal and visual material over 3 weeks by comparison with matched control subjects (p < 0.001). They also showed loss of autobiographical memories for events extending back over 40 years (p < 0.05).
INTERPRETATION: We propose that transient epileptic amnesia is a distinctive epilepsy syndrome, typically misdiagnosed at presentation and associated with accelerated long-term forgetting and autobiographical amnesia. The syndrome is of clinical and theoretic importance.

PMID 17444534  Ann Neurol. 2007 Jun;61(6):587-98. doi: 10.1002/ana.211・・・
著者: E B Larson, B V Reifler, S M Sumi, C G Canfield, N M Chinn
雑誌名: Arch Intern Med. 1986 Oct;146(10):1917-22.
Abstract/Text We studied the components of the diagnostic evaluation in 200 patients older than 60 years of age with suspected dementia who received standardized diagnostic evaluation and follow-up. The most common dementia diagnoses were Alzheimer's-type dementia (74.5%) and dementia due to toxic effects of drugs (9.5%). Eleven patients with hypothyroidism, metabolic encephalopathies due to hyponatremia, hyperparathyroidism, and hypoglycemia required laboratory tests for diagnosis, whereas the other dementia diagnoses were made primarily on the basis of data available on the history and physical and neurologic examinations. The complete blood cell count, blood chemistry battery (especially sodium, calcium, and glucose concentrations), and thyroid function tests were of definite value for the diagnosis of unsuspected disease and were useful as routine tests in evaluating patients for dementia. A careful history and physical examination accompanied by complete blood cell count, chemistry battery, and a thyroid function test would have been effective in diagnosing treatable illnesses causing cognitive impairment. Other diagnostic tests could have been used selectively based on results of the examination and screening tests. Estimated diagnostic charges from a selective approach would be 25% to 34% of those for the "routine" evaluation.

PMID 3767535  Arch Intern Med. 1986 Oct;146(10):1917-22.
著者: D B Carr, S Gray, J Baty, J C Morris
雑誌名: Neurology. 2000 Dec 12;55(11):1724-6.
Abstract/Text Self-reported versus informant-reported memory problems in nondemented elderly adults and in individuals with very mild and mild dementia of the Alzheimer type (DAT) were correlated with cognitive outcomes. No significant correlations were found between self-reported memory complaints and cognitive performance or (in controls) later development of dementia. In contrast, informant-reported memory loss distinguished nondemented from demented individuals and predicted future diagnosis of DAT.

PMID 11113230  Neurology. 2000 Dec 12;55(11):1724-6.
著者: Leslie A Wei, Michael A Fearing, Eliezer J Sternberg, Sharon K Inouye
雑誌名: J Am Geriatr Soc. 2008 May;56(5):823-30. doi: 10.1111/j.1532-5415.2008.01674.x. Epub 2008 Apr 1.
Abstract/Text OBJECTIVES: To examine the psychometric properties, adaptations, translations, and applications of the Confusion Assessment Method (CAM), a widely used instrument and diagnostic algorithm for identification of delirium.
DESIGN: Systematic literature review.
SETTING: Not applicable.
MEASUREMENTS: Electronic searches of PubMED, EMBASE, PsychINFO, CINAHL, Ageline, and Google Scholar, augmented by reviews of reference listings, were conducted to identify original English-language articles using the CAM from January 1, 1991, to December 31, 2006. Two reviewers independently abstracted key information from each article.
PARTICIPANTS: Not applicable.
RESULTS: Of 239 original articles, 10 (4%) were categorized as validation studies, 16 (7%) as adaptations, 12 (5%) as translations, and 222 (93%) as applications. Validation studies evaluated performance of the CAM against a reference standard. Results were combined across seven high-quality studies (N=1,071), demonstrating an overall sensitivity of 94% (95% confidence interval (CI)=91-97%) and specificity of 89% (95% CI=85-94%). The CAM has been adapted for use in the intensive care unit, emergency, and institutional settings and for scoring severity and subsyndromal delirium. The CAM has been translated into 10 languages where published articles are available. In application studies, CAM-rated delirium is most commonly used as a risk factor or outcome but also as an intervention or reference standard.
CONCLUSION: The CAM has helped to improve identification of delirium in clinical and research settings. To optimize performance, the CAM should be scored based on observations made during formal cognitive testing, and training is recommended. Future action is needed to optimize use of the CAM and to improve the recognition and management of delirium.

PMID 18384586  J Am Geriatr Soc. 2008 May;56(5):823-30. doi: 10.1111/j・・・
著者: D S Knopman, S T DeKosky, J L Cummings, H Chui, J Corey-Bloom, N Relkin, G W Small, B Miller, J C Stevens
雑誌名: Neurology. 2001 May 8;56(9):1143-53.
Abstract/Text OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly.
BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis.
METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia?
RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline).
CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

PMID 11342678  Neurology. 2001 May 8;56(9):1143-53.
著者: J E Graham, K Rockwood, B L Beattie, I McDowell, R Eastwood, S Gauthier
雑誌名: Neuroepidemiology. 1996;15(5):246-56.
Abstract/Text Standardization of diagnostic procedures for cognitive impairment in large epidemiologic surveys remains difficult. This paper reports results of diagnostic standardization in a subsample of 2,914 elderly (age 65 years+) Canadians from the Canadian Study of Health and Aging (CSHA; n = 10,263). The objectives were to measure the consistency of the CSHA diagnosis as a test of validity; to assess inter-rater reliability, and to assess the impact of neuropsychological data on the diagnosis of dementia. The CSHA clinical assessment included a nurse's examination, Modified Mini-Mental Status (3MS) exam and Cambridge Mental Disorders Examination, neuropsychological tests, medical history and examination, and laboratory investigations. A final diagnosis was reached in a consensus conference which incorporated preliminary diagnoses from both physicians and neuropsychologists. Computer algorithms, which were developed to check consistency between the clinical observations and the final diagnosis, demonstrated 98% concordance with DSM-III-R criteria for dementia and 92% with NINCDS-ADRADA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for probable Alzheimer's disease. Inter-rater agreement was high: kappa = 0.81 for dementia/no dementia; kappa = 0.74 for normal/cognitive impairment, not dementia/ dementia. Comparisons of diagnoses between raters by clinical specialty revealed few systematic differences. The impact of neuropsychological input on the physician's diagnosis was most marked in the borderline cases between diagnostic categories.

PMID 8878077  Neuroepidemiology. 1996;15(5):246-56.
著者: K A Jobst, L P Barnetson, B J Shepstone
雑誌名: Int Psychogeriatr. 1998 Sep;10(3):271-302.
Abstract/Text In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m-hexamethyl-propylene amineoxime (99mTC-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49% sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both "probable-AD" and "possible-AD" was 61% specific, 96% sensitive, and 85% accurate. DSM-III-R criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases and including the 105 living, elderly controls, the diagnostic accuracy of the Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89% sensitivity, 80% specificity, and 83% accuracy; and the combination of the two was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74% sensitive but yielded 40% false positives in the histologically confirmed series. The diagnostic accuracy afforded by this method of CT and SPECT used alone is better than that of any established clinical criteria and reveals that the combination of MTL atrophy and parietotemporal hypoperfusion is common in AD, much less common in other dementias, and rare in normal controls. In the NINCDS-ADRDA criteria "possible-AD" cases, the combination of CT and SPECT findings alone were better in all diagnostic indices than the presence of Apo E4 alone in predicting AD. The frequent occurrence of MTL atrophy in AD and also in other "non-AD" dementias later in the course of the disease suggests the concept of medial temporal lobe dementia. This could explain some of the overlap of clinical profiles in the dementias, particularly as the dementia progresses, making clinical differential diagnosis difficult. In this context, the use of SPECT can significantl

PMID 9785148  Int Psychogeriatr. 1998 Sep;10(3):271-302.
著者: Tracey Holsinger, Janie Deveau, Malaz Boustani, John W Williams
雑誌名: JAMA. 2007 Jun 6;297(21):2391-404. doi: 10.1001/jama.297.21.2391.
Abstract/Text CONTEXT: While as many as 5 million individuals in the United States have dementia, many others have memory complaints. Brief tests to screen for cognitive impairment could help guide dementia diagnosis.
OBJECTIVE: To review the literature concerning the practicality and accuracy of brief cognitive screening instruments in primary care.
DATA SOURCES: A search of MEDLINE (including data from AIDSLINE, BioethicsLine, and HealthSTAR) and psycINFO was conducted from January 2000 through April 2006 to update previous reviews.
STUDY SELECTION: Studies of patients aged 60 years and older and use of an acceptable criterion standard to diagnose dementia were considered.
DATA EXTRACTION: Studies were assessed by 2 independent reviewers for eligibility and quality. A third independent reviewer adjudicated disagreements. Data for likelihood ratios (LRs) were extracted.
DATA SYNTHESIS: Twenty-nine studies using 25 different screening instruments met inclusion criteria; some studies evaluated several different instruments, thus, information could be examined for 38 unique instrument/study combinations.
RESULTS: For the commonly used Mini-Mental State Examination, the median LR for a positive result was 6.3 (95% confidence interval [CI], 3.4-47.0) and the median LR for a negative result was 0.19 (95%CI, 0.06-0.37). Briefer approaches are available but have not been studied as frequently. Reports from an informant that the patient has memory loss yields an LR of 6.5 (95% CI, 4.4-9.6) for dementia. The Memory Impairment Screen takes 4 minutes to ask 4 items and has an LR for a positive result of 33 (95% CI, 15.0-72.0) and an LR for a negative result is 0.08 (95% CI, 0.02-0.3). Clock drawings are helpful in 1- to 3-minute forms, but must be scored appropriately and sensitivity to mild forms of impairment can be low.
CONCLUSIONS: Clinicians should select 1 primary tool based on (1) the population receiving care; (2) an awareness of the effects of educational level, race, and age on scoring; and (3) consideration of adding 1 or 2 other tools for special situations as needed.

PMID 17551132  JAMA. 2007 Jun 6;297(21):2391-404. doi: 10.1001/jama.29・・・
著者: W Freidl, R Schmidt, W J Stronegger, A Irmler, B Reinhart, M Koch
雑誌名: J Clin Epidemiol. 1996 Jan;49(1):73-8.
Abstract/Text Age and education have been found to affect the Mini Mental State Examination (MMSE) score of elderly normals, but there have been no studies assessing the influence of environmental and behavioral factors on this test. We therefore administered the MMSE to 1437 normal elderly subjects in the setting of a stroke prevention study and correlated their results to 16 sociodemographic, environmental, and behavioral factors, and vascular risk factors. Study statistics composed of a multiple logistic regression analysis and graphical models revealed the relations between variables in greater detail. Logistic regression yielded education level, occupational status, living as a single, general life stress, physical strain, and physical inactivity to be independent predictors of the MMSE score. Age was not included in this model. Graphical models demonstrated similar results, but did not include living as a single and physical inactivity. As shown in our independence graph, general life stress is the crucial predictor and links other environmental and sociodemographic variables with the test performance of elderly normals.

PMID 8598514  J Clin Epidemiol. 1996 Jan;49(1):73-8.
著者: F Grigoletto, G Zappalà, D W Anderson, B D Lebowitz
雑誌名: Neurology. 1999 Jul 22;53(2):315-20.
Abstract/Text BACKGROUND: Although the Mini-Mental State Examination (MMSE) is widely used in clinical practice, few norms exist for healthy populations covering a broad range of ages.
OBJECTIVE: To obtain MMSE norms specific for age, gender, and education in healthy adults.
METHODS: From the population registers of seven communities across Italy, we selected a proportionate random sample of residents age 20 to 79 years to evaluate their health status with respect to conditions affecting cognitive performance. This sample yielded 908 persons who were deemed to be without cognitive impairment and who were then given the MMSE. We calculated fifth percentile norms and presented them as step functions. We then validated the norms as a screening tool for dementia in persons age 65 to 79 years. The validation was based on unpublished data from a separate study and involved estimates of sensitivity and specificity.
RESULTS: The norms declined with advancing age, especially for less educated women. Given any age and sex, the norms were higher for individuals with higher educational levels. In screening for dementia, the norms had a sensitivity of 85% and a specificity of 89%.
CONCLUSIONS: When using MMSE scores, it is important to account for age, gender, and education, especially in populations where the educational level is low. Expressing MMSE norms as step functions provides an easy-to-use tool for neurologists and other clinicians.

PMID 10430420  Neurology. 1999 Jul 22;53(2):315-20.
著者: K W Kim, D Y Lee, J H Jhoo, J C Youn, Y J Suh, Y H Jun, E H Seo, J I Woo
雑誌名: Dement Geriatr Cogn Disord. 2005;19(5-6):324-30. doi: 10.1159/000084558. Epub 2005 Mar 22.
Abstract/Text To compare the diagnostic accuracies of the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental Status Examination (MMSE) for Alzheimer's diseases (AD), we administered them simultaneously to 82 AD patients and 82 age- and sex-matched nondemented control subjects. The area under the receiver operator curve (AUC) for AD of the HDS-R (AUC(HDS-R)) and MMSE (AUC(MMSE)) were bigger than 0.90 indicating that both tests are useful for detecting AD. However, AUC(HDS-R) (0.952) was significantly larger than that of the AUC(MMSE )(0.902) regardless of the educational level of the subjects, indicating that the HDS-R is more accurate than MMSE in diagnosing AD. Moreover, the superiority of the HDS-R (AUC(HDS-R) = 0.894) to the MMSE (AUC(MMSE) = 0.704) remained significant in mild AD patients alone, who are the focus of screening. In conclusion, the HDS-R is better than the MMSE as a screening instrument for AD.

PMID 15785033  Dement Geriatr Cogn Disord. 2005;19(5-6):324-30. doi: 1・・・
著者: A M Clarfield
雑誌名: Ann Intern Med. 1988 Sep 15;109(6):476-86.
Abstract/Text Thirty-two studies (2889 subjects) that investigated the prevalence of the causes of dementia were critically reviewed. Particular attention was paid to potential and actual reversibility. Although dementia manifests itself primarily in old age (particularly age 75 and older), the mean age of patients for the studies that reported age data (56%) was 72.3 years. Twenty-five studies originated from secondary or tertiary centers, and four were community-based. Dementias consisted of Alzheimer disease, 56.8%; multi-infarct, 13.3%; depression, 4.5%; alcoholic, 4.2%; and drugs, 1.5%. No single other cause contributed more than 1.6% of the cases. Potentially reversible causes made up 13.2% of all cases. However, the more important question of whether patients with potentially reversible causes were followed and reversal actually seen was not always examined. In 11 studies (34%) that provided follow-up, 11% of dementias resolved, either partially (8%) or fully (3%). The commonest reversible causes were drugs, 28.2%; depression, 26.2%; and metabolic, 15.5%. Due to the presence of various biases (selection, lack of "blinded" investigators, and others) in the surveyed works, it is probable that the true incidence of reversible dementias in the community is even lower than that reported. Research implications as well as a conservative approach to the workup of a new case of dementia are offered.

PMID 3046450  Ann Intern Med. 1988 Sep 15;109(6):476-86.
著者: Bruce Arroll, Natalie Khin, Ngaire Kerse
雑誌名: BMJ. 2003 Nov 15;327(7424):1144-6. doi: 10.1136/bmj.327.7424.1144.
Abstract/Text OBJECTIVE: To determine the diagnostic accuracy of two verbally asked questions for screening for depression.
DESIGN: Cross sectional criterion standard validation study.
SETTING: 15 general practices in New Zealand.
PARTICIPANTS: 421 consecutive patients not taking psychotropic drugs.
MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios of the two questions compared with the computerised composite international diagnostic interview.
RESULTS: The two screening questions showed a sensitivity and specificity of 97% (95% confidence interval, 83% to 99%) and 67% (62% to 72%), respectively. The likelihood ratio for a positive test was 2.9 (2.5 to 3.4) and the likelihood ratio for a negative test was 0.05 (0.01 to 0.35). Overall, 37% (157/421) of the patients screened positive for depression.
CONCLUSION: Two verbally asked questions for screening for depression would detect most cases of depression in general practice. The questions have the advantage of brevity. As treatment is more likely when doctors make the diagnosis, these questions may have even greater utility.

PMID 14615341  BMJ. 2003 Nov 15;327(7424):1144-6. doi: 10.1136/bmj.327・・・
著者: D A Fiellin, M C Reid, P G O'Connor
雑誌名: Arch Intern Med. 2000 Jul 10;160(13):1977-89.
Abstract/Text BACKGROUND: Primary care physicians can play a unique role in recognizing and treating patients with alcohol problems.
OBJECTIVE: To evaluate the accuracy of screening methods for alcohol problems in primary care.
METHODS: We performed a search of MEDLINE for years 1966 through 1998. We included studies that were in English, were performed in primary care, and reported the performance characteristics of screening methods for alcohol problems against a criterion standard. Two reviewers appraised all articles for methodological content and results.
RESULTS: Thirty-eight studies were identified. Eleven screened for at-risk, hazardous, or harmful drinking; 27 screened for alcohol abuse and dependence. A variety of screening methods were evaluated. The Alcohol Use Disorders Identification Test (AUDIT) was most effective in identifying subjects with at-risk, hazardous, or harmful drinking (sensitivity, 51%-97%; specificity, 78%-96%), while the CAGE questions proved superior for detecting alcohol abuse and dependence (sensitivity, 43%-94%; specificity, 70%-97%). These 2 formal screening instruments consistently performed better than other methods, including quantity-frequency questions. The studies inconsistently adhered to methodological standards for diagnostic test research: 3 (8%) provided a full description of patient spectrum (demographics and comorbidity), 30 (79%) avoided workup bias, 12 (of 34 studies [35%]) avoided review bias, and 21 (55%) performed an analysis in pertinent clinical subgroups.
CONCLUSIONS: Despite methodological limitations, the literature supports the use of formal screening instruments over other clinical measures to increase the recognition of alcohol problems in primary care. Future research in this field will benefit from increased adherence to methodological standards for diagnostic tests.

PMID 10888972  Arch Intern Med. 2000 Jul 10;160(13):1977-89.
著者: Ankur Sachdeva, Mina Chandra, Mona Choudhary, Prabhoo Dayal, Kuljeet Singh Anand
雑誌名: Int J High Risk Behav Addict. 2016 Sep;5(3):e27976. doi: 10.5812/ijhrba.27976. Epub 2016 Feb 7.
Abstract/Text CONTEXT: Alcohol consumption has escalated rapidly in many countries over the past decade. Evidence suggests a correlation between alcohol use and cognitive decline. We have systematically reviewed the concept and controversies, epidemiology, nosology, neuropathology and neurobiology, neuropsychology and management updates of alcohol-related dementia (ARD) in this paper.
EVIDENCE ACQUISITION: We retrieved papers for this review by searching the PubMed database for terms "alcohol and dementia", "alcohol and cognitive impairment", and "alcohol and wernicke-korsakoff" mentioned in the title of the published papers. A total of 131 studies showed up. Appropriate studies were shortlisted and included (n = 72). Cross-references if relevant were considered from the selected studies. Eligible articles were fully read by the authors and the results were compiled.
RESULTS: The prolonged and excessive use of alcohol may lead to structural and functional brain damage, leading to ARD. The cognitive deficits are most frequently observed in domains of visuospatial functions, memory and executive tasks, with a potential of partial recovery if abstinence is maintained. However, there are doubts regarding the etiopathogenesis, nosological status, prevalence and diagnostic criteria for ARD, due to difficulty in assessment and various confounding factors.
CONCLUSIONS: With growing cohort of young and middle-aged people, there is a probable risk of upsurge of ARD. Presently, there are dilemmas over the diagnosis of independent ARD. Thus, there is a need to develop evidence-based guidelines for diagnosis and management of ARD through further systematic studies.

PMID 27818965  Int J High Risk Behav Addict. 2016 Sep;5(3):e27976. doi・・・
著者: A O Hebb, M D Cusimano
雑誌名: Neurosurgery. 2001 Nov;49(5):1166-84; discussion 1184-6.
Abstract/Text OBJECTIVE: Patient selection for cerebrospinal fluid diversion is difficult, because idiopathic normal pressure hydrocephalus (INPH) mimics other neurodegenerative disorders and no findings reliably predict outcome. The literature was reviewed to identify diagnostic criteria that predict shunt response and to formulate prognostic expectations.
METHODS: MEDLINE was searched, and 44 articles meeting predetermined criteria were included.
RESULTS: Clinical series were frequently retrospective with small patient numbers and unstandardized outcome evaluation. Clinical findings suggestive of shunt responsiveness were the complete triad (gait disturbance, urinary incontinence, and dementia) with early gait disturbance. Degree of hydrocephalus was not correlated with clinical improvement. Reduction of the subcortical low-blood flow area was correlated with improvement in three small studies. Clinical response to prolonged cerebrospinal fluid drainage predicted shunt outcome in all cases in two small series. Overall, 59% (range, 24-100%) of patients improved after shunting, and 29% (range, 10-100%) of patients experienced prolonged improvement. Complications occurred in 38% (range, 5-100%) of patients, additional surgery was required in 22% (range, 0-47%) of patients, and there was a 6% (range, 0-35%) combined rate of permanent neurological deficit and death.
CONCLUSION: Shunting INPH is associated with an approximately 29% rate of significant improvement and a 6% significant complication rate. Enlargement of the subcortical low-flow area and clinical improvement secondary to prolonged lumbar drainage may provide additive predictive value above clinical and computed tomographic criteria. A multicenter clinical trial that focuses on the value of ancillary tests, defines the clinical course of a patient with a ventriculoperitoneal shunt, and evaluates the cost effectiveness of shunting INPH is needed to better describe outcome from shunting in INPH.

PMID 11846911  Neurosurgery. 2001 Nov;49(5):1166-84; discussion 1184-6・・・
著者: G Webster Ross, James D Bowen
雑誌名: Med Clin North Am. 2002 May;86(3):455-76.
Abstract/Text The initial approach to the patient with memory complaints should consist of a focused history, mental status examination, and functional assessment. Patients with MCI should be monitored every 6 to 12 months for conversion to dementia. Delirium, depression, amnestic disorders, and aphasias should be considered in the differential diagnosis of memory impairment. Once a diagnosis of dementia is made, patients should have a brain CT or MRI scan and laboratory tests to assist with determining the cause. It is crucial that dementia be recognized and evaluated at the earliest stage so as to begin appropriate therapy and allow the patient to have a role in management decisions. In the future, therapies for MCI may prevent conversion to dementia. The need for early recognition makes the development of diagnostic tools, such as quantitative or functional neuroimaging, and genetic or clinical biologic markers essential.

PMID 12168555  Med Clin North Am. 2002 May;86(3):455-76.
著者: E Tedeschi, S G Hasselbalch, G Waldemar, M Juhler, P Høgh, S Holm, L Garde, L L Knudsen, L Klinken, F Gjerris
雑誌名: J Neurol Neurosurg Psychiatry. 1995 Dec;59(6):608-15.
Abstract/Text The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series.

PMID 7500099  J Neurol Neurosurg Psychiatry. 1995 Dec;59(6):608-15.
著者: R Indra, S S Patil, R Joshi, M Pai, S P Kalantri
雑誌名: J Postgrad Med. 2004 Jan-Mar;50(1):7-11; discussion 11.
Abstract/Text BACKGROUND: Hypothyroidism is a common, potentially treatable endocrine disorder. Since hypothyroidism is not always associated with the signs and symptoms typically attributed to it, the diagnosis is often missed. Conversely, patients with typical signs and symptoms may not have the disease when laboratory tests are performed.
AIMS: We aimed to determine the accuracy of physical examination in the diagnosis of hypothyroidism.
SETTING AND DESIGN: Prospective, hospital-based, cross-sectional diagnostic study.
MATERIAL AND METHODS: Consecutive outpatients from the medicine department were screened and an independent comparison of physical signs (coarse skin, puffy face, slow movements, bradycardia, pretibial oedema and ankle reflex) against thyroid hormone assay (TSH and FT4) was performed.
STATISTICAL ANALYSIS: Diagnostic accuracy was measured as sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and positive and negative predictive values.
RESULTS: Of the 1450 patients screened, 130 patients (102 women and 28 men) underwent both clinical examination and thyroid function tests. Twenty-three patients (18%) were diagnosed to have hypothyroidism by thyroid hormone assays. No single sign could easily discriminate a euthyroid from a hypothyroid patient (range of positive likelihood ratio (LR+) 1.0 to 3.88; range of negative likelihood ratio (LR-): 0.42 to 1.0). No physical sign generated a likelihood ratio large enough to increase the post-test probability significantly. The combination of signs that had the highest likelihood ratios (coarse skin, bradycardia and delayed ankle reflex) was associated with modest accuracy (LR+ 3.75; LR- 0.48).
CONCLUSION: Clinicians cannot rely exclusively on physical examination to confirm or rule out hypothyroidism. Patients with suspected hypothyroidism require a diagnostic workup that includes thyroid hormone assays.

PMID 15047991  J Postgrad Med. 2004 Jan-Mar;50(1):7-11; discussion 11.・・・
著者: C Frank
雑誌名: Can Fam Physician. 1998 Jul;44:1489-95.
Abstract/Text OBJECTIVE: To review Canadian Consensus Conference on the Assessment of Dementia (CCCAD) guidelines for laboratory evaluation of dementia, and to make recommendations to family physicians based on these guidelines and other literature.
DATA SOURCES: English-language data sources from 1992 to March 1997 were searched on MEDLINE using the MeSH headings dementia, dementia/diagnosis, and cognition. Key words relating to specific laboratory tests or conditions, such as neurosyphilis or vitamin B12, were also used.
STUDY SELECTION: Original research articles using prospective and retrospective methods were accepted. Articles reviewing the general investigation of potentially reversible dementia were included, as were articles looking at the sensitivity, specificity, and utility of investigations for specific conditions causing dementia.
SYNTHESIS: Family physicians are not always aware of CCCAD recommendations for the investigation of dementia. There was C-level evidence for use of CCCAD core investigations (complete blood count and electrolyte, glucose, calcium, and thyroid levels) and for tests to be done "when the clinical situation warrants" (B12 levels, computed tomography scan of the head, and testing for syphilis).
CONCLUSIONS: The CCCAD guidelines were supported by most literature on the workup of dementia. Prospective cohort studies suggest use of clinical judgment in ordering laboratory investigations. No controlled trials were available, and most recommendations arose from consensus rather than from research evidence. The prevalence of reversible dementias is likely lower than previously believed, which further supports a selective approach to investigations. Identification of reversible causes and exacerbating factors is still the goal.

PMID 9678278  Can Fam Physician. 1998 Jul;44:1489-95.
著者: J Lindenbaum, E B Healton, D G Savage, J C Brust, T J Garrett, E R Podell, P D Marcell, S P Stabler, R H Allen
雑誌名: N Engl J Med. 1988 Jun 30;318(26):1720-8. doi: 10.1056/NEJM198806303182604.
Abstract/Text Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.

PMID 3374544  N Engl J Med. 1988 Jun 30;318(26):1720-8. doi: 10.1056/・・・
著者: Rachel A Whitmer, Andrew J Karter, Kristine Yaffe, Charles P Quesenberry, Joseph V Selby
雑誌名: JAMA. 2009 Apr 15;301(15):1565-72. doi: 10.1001/jama.2009.460.
Abstract/Text CONTEXT: Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes.
OBJECTIVE: To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years.
DESIGN, SETTING, AND PATIENTS: A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California.
MAIN OUTCOME MEASURE: Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease.
RESULTS: At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55).
CONCLUSIONS: Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.

PMID 19366776  JAMA. 2009 Apr 15;301(15):1565-72. doi: 10.1001/jama.20・・・
著者: K Mattishent, Y K Loke
雑誌名: Diabetes Obes Metab. 2016 Feb;18(2):135-41. doi: 10.1111/dom.12587. Epub 2015 Dec 8.
Abstract/Text AIMS: To examine the bi-directional relationship, whereby hypoglycaemia is a risk factor for dementia, and where dementia increases risk of hypoglycaemia in older patients with diabetes mellitus treated with glucose-lowering agents.
METHODS: We searched MEDLINE and EMBASE over a 10-year span from 2005 to 2015 (with automated PubMed updates to August 2015) for observational studies of the association between hypoglycaemia and cognitive impairment or dementia in participants aged >55 years. Assessment of study validity was based on ascertainment of hypoglycaemia, dementia and risk of confounding. We conducted random effects inverse variance meta-analyses, and assessed heterogeneity using the I(2) statistic.
RESULTS: We screened 1177 citations, and selected 12 studies, of which nine were suitable for meta-analysis. There were a total of 1,439,818 participants, with a mean age of 75 years. Meta-analysis of five studies showed a significantly increased risk of dementia in patients who had hypoglycaemic episodes: pooled odds ratio 1.68 [95% confidence interval (CI) 1.45, 1.95]. We also found a significantly increased risk of hypoglycaemia in patients with dementia: pooled odds ratio from five studies 1.61 (95% CI 1.25, 2.06). Limitations of the study were heterogeneity in the meta-analysis, and uncertain ascertainment of dementia and hypoglycaemic outcomes and temporal relationships. Publication bias may have favoured the reporting of more significant findings.
CONCLUSIONS: Our meta-analysis shows a bi-directional relationship between cognitive impairment and hypoglycaemia in older patients. Glucose-lowering therapy should be carefully tailored and monitored in older patients who are susceptible to cognitive decline.

© 2015 John Wiley & Sons Ltd.
PMID 26446922  Diabetes Obes Metab. 2016 Feb;18(2):135-41. doi: 10.111・・・
著者: Brian M Frier
雑誌名: Nat Rev Endocrinol. 2014 Dec;10(12):711-22. doi: 10.1038/nrendo.2014.170. Epub 2014 Oct 7.
Abstract/Text Hypoglycaemia is a frequent adverse effect of treatment of diabetes mellitus with insulin and sulphonylureas. Fear of hypoglycaemia alters self-management of diabetes mellitus and prevents optimal glycaemic control. Mild (self-treated) and severe (requiring help) hypoglycaemia episodes are more common in type 1 diabetes mellitus but people with insulin-treated type 2 diabetes mellitus are also exposed to frequent hypoglycaemic events, many of which occur during sleep. Hypoglycaemia can disrupt many everyday activities such as driving, work performance and leisure pursuits. In addition to accidents and physical injury, the morbidity of hypoglycaemia involves the cardiovascular and central nervous systems. Whereas coma and seizures are well-recognized neurological sequelae of hypoglycaemia, much interest is currently focused on the potential for hypoglycaemia to cause dangerous and life-threatening cardiac complications, such as arrhythmias and myocardial ischaemia, and whether recurrent severe hypoglycaemia can cause permanent cognitive impairment or promote cognitive decline and accelerate the onset of dementia in middle-aged and elderly people with diabetes mellitus. Prevention of hypoglycaemia is an important part of diabetes mellitus management and strategies include patient education, glucose monitoring, appropriate adjustment of diet and medications in relation to everyday circumstances including physical exercise, and the application of new technologies such as real-time continuous glucose monitoring, modified insulin pumps and the artificial pancreas.

PMID 25287289  Nat Rev Endocrinol. 2014 Dec;10(12):711-22. doi: 10.103・・・
著者: M Ganguli, L A Burmeister, E C Seaberg, S Belle, S T DeKosky
雑誌名: Biol Psychiatry. 1996 Oct 15;40(8):714-25. doi: 10.1016/0006-3223(95)00489-0.
Abstract/Text We report on 194 individuals (96 men and 98 women), aged 65 and over, who had dementia assessments and basal TSH measurements as part of an ongoing epidemiological study of dementing disorders in a larger population. Dementia was diagnosed according to DSM-III-R and measured by the Clinical Dementia Rating scale; CDR scores of 0, 0.5, and > or = 1, represent individuals with no dementia (n = 122), possible dementia (n = 29), and definite dementia (n = 43), respectively. The odds ratio for the association of elevated TSH with definite dementia (CDR > or = 1) was 3.8 (95% confidence interval = 1.6, 9.1) and with possible and/or definite dementia (CDR > or = 0.5) was 3.8 (95% confidence interval = 1.6, 9.2), after adjusting for the effects of age, gender, and level of education. This is the first community-based study to report an association between TSH elevation and dementia. Our findings are consistent with recent evidence that subclinical hypothyroidism is associated with cognitive impairment, and that thyroidal state may influence cerebral metabolism.

PMID 8894063  Biol Psychiatry. 1996 Oct 15;40(8):714-25. doi: 10.1016・・・
著者: J T Dietch
雑誌名: West J Med. 1983 Jun;138(6):835-7.
Abstract/Text In assessing the clinical value of computerized tomographic (CT) scanning in elderly patients with dementia, only one of 100 patients with dementia of insidious onset and no other abnormal neurologic signs was found to have a potentially treatable disorder. In a second group of 100 patients with dementia of abrupt onset or with additional abnormal neurologic signs, 12 were found to have a lesion that potentially required medical or surgical intervention. We conclude that a subgroup of patients with dementia, representing about a third of demented patients in our hospital, are unlikely to benefit from CT scanning.

PMID 6613111  West J Med. 1983 Jun;138(6):835-7.
著者: H Chui, Q Zhang
雑誌名: Neurology. 1997 Oct;49(4):925-35.
Abstract/Text OBJECTIVE: This study examined the usefulness of the "Practice Parameters for the Evaluation of Dementia," published by the Quality Standards Subcommittee of the American Academy of Neurology (1994). The Practice Parameters are stratified according to three levels of certainty (standards, guidelines, and options), and suggest indications for the use of neuroimaging studies.
METHODS: We reviewed 119 consecutive cases referred for assessment of memory loss to a university-affiliated interdisciplinary clinic. We assessed the diagnostic value of laboratory, neuropsychological, and neuroimaging studies above the standard history, neurologic, and mental status examinations. We also assessed the sensitivity and specificity of four clinical indicators (i.e., early symptom onset, noninsidious course, focal neurologic signs or symptoms, and gait disturbance) for predicting the diagnostic utility of neuroimaging studies.
RESULTS: The largest changes in diagnostic categories between the standard and the comprehensive diagnostic process was a 9% decrease in the diagnosis of Alzheimer's disease, a 6% increase in the diagnosis of mixed dementia (due largely to laboratory studies), and a 4% increase in the diagnosis of vascular dementia (due to neuroimaging). The clinical indicators were 82% sensitive and 50% specific in predicting that neuroimaging studies would change the diagnosis. In six cases, meaningful neuroimaging findings were not associated with any clinical indicator (5% false negatives). In 43 cases, neuroimaging provided no significant clinical findings despite the presence of an indicator (36% false positives).
CONCLUSIONS: In this convenience sample, diagnostic accuracy was improved to a comparable degree by laboratory and neuroimaging studies, although at a significant difference in cost. Use of the four clinical indicators would have reduced the frequency of neuroimaging studies by 33% but missed clinically meaningful information in 5%. Although imperfect, the Practice Parameters represent a first step toward improving the cost effectiveness of the dementia work-up.

PMID 9339669  Neurology. 1997 Oct;49(4):925-35.
著者: W Jagust, R Thisted, M D Devous, R Van Heertum, H Mayberg, K Jobst, A D Smith, N Borys
雑誌名: Neurology. 2001 Apr 10;56(7):950-6. doi: 10.1212/wnl.56.7.950.
Abstract/Text OBJECTIVE: Numerous studies have suggested that temporoparietal hypoperfusion seen on brain imaging with SPECT may be useful in diagnosing AD during life. However, these studies have often been limited by lack of pathologic validation and unrepresentative samples. The authors performed this study to determine whether SPECT imaging provides diagnostically useful information in addition to that obtained from a clinical examination.
METHODS: Clinical data and SPECT images were collected prospectively, and patients were followed to autopsy. Clinical history, pathologic findings, and SPECT images were each evaluated by raters blind to other features, and clinical and SPECT diagnoses were compared with pathologic diagnoses. The study population consisted of 70 patients with dementia, followed to autopsy; 14 controls followed to autopsy; and 71 controls (no autopsy performed). The primary outcome was the likelihood of a pathologic diagnosis of AD given a positive clinical diagnosis, a positive SPECT diagnosis, and both.
RESULTS: When all participants (patients and controls) were included in the analysis, the clinical diagnosis of "probable" AD was associated with an 84% likelihood of pathologic AD. A positive SPECT scan raised the likelihood of AD to 92%, whereas a negative SPECT scan lowered the likelihood to 70%. SPECT was more useful when the clinical diagnosis was "possible" AD, with the likelihood of 67% without SPECT, 84% with a positive SPECT, and 52% with a negative SPECT. Similar results were found when only patients with dementia were included in the analysis.
CONCLUSIONS: In the evaluation of dementia, SPECT imaging can provide clinically useful information indicating the presence of AD in addition to the information that is obtained from clinical evaluation.

PMID 11294935  Neurology. 2001 Apr 10;56(7):950-6. doi: 10.1212/wnl.56・・・
著者: Mitsuhiro Yoshita, Heii Arai, Hiroyuki Arai, Tetsuaki Arai, Takashi Asada, Hiroshige Fujishiro, Haruo Hanyu, Osamu Iizuka, Eizo Iseki, Kenichi Kashihara, Kenji Kosaka, Hirotaka Maruno, Katsuyoshi Mizukami, Yoshikuni Mizuno, Etsuro Mori, Kenichi Nakajima, Hiroyuki Nakamura, Seigo Nakano, Kenji Nakashima, Yoshiyuki Nishio, Satoshi Orimo, Miharu Samuraki, Akira Takahashi, Junichi Taki, Takahiko Tokuda, Katsuya Urakami, Kumiko Utsumi, Kenji Wada, Yukihiko Washimi, Junichi Yamasaki, Shouhei Yamashina, Masahito Yamada
雑誌名: PLoS One. 2015;10(3):e0120540. doi: 10.1371/journal.pone.0120540. Epub 2015 Mar 20.
Abstract/Text BACKGROUND AND PURPOSE: Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer's disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study.
METHODS: We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system.
RESULTS: Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio.
CONCLUSIONS: Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.

PMID 25793585  PLoS One. 2015;10(3):e0120540. doi: 10.1371/journal.pon・・・
著者: Alan J Thomas, Johannes Attems, Sean J Colloby, John T O'Brien, Ian McKeith, Rodney Walker, Lean Lee, David Burn, Debra J Lett, Zuzana Walker
雑誌名: Neurology. 2017 Jan 17;88(3):276-283. doi: 10.1212/WNL.0000000000003512. Epub 2016 Dec 9.
Abstract/Text OBJECTIVE: To conduct a validation study of 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard.
METHODS: Patients >60 years of age with dementia who had undergone 123I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent 123I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria.
RESULTS: Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis, 123I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal 123I-FP-CIT imaging.
CONCLUSIONS: This large autopsy analysis of 123I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal 123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 123I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB.

Copyright © 2016 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PMID 27940650  Neurology. 2017 Jan 17;88(3):276-283. doi: 10.1212/WNL.・・・
著者: Jian-Fang Ma, Li-hua Liu, Yu Zhang, Ying Wang, Yu-Lei Deng, Yue Huang, Gang Wang, Wei Xu, Pei-Jing Cui, Qing-Zhou Fei, Jian-Qing Ding, Hui-Dong Tang, Sheng-Di Chen
雑誌名: Am J Alzheimers Dis Other Demen. 2011 Dec;26(8):627-30. doi: 10.1177/1533317511432735. Epub 2012 Jan 31.
Abstract/Text OBJECTIVE: We conducted a case-control study to investigate whether clusterin polymorphism (rs11136000) was associated with late-onset Alzheimer's disease in Chinese Han population.
METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was performed on genotype rs11136000 and APOEε4 in 127 patients with late-onset Alzheimer's disease and 143 control individuals. Previous published data from other Chinese samples was also included for further meta-analysis.
RESULTS: APOEε4 was demonstrated to increase the risk of Alzheimer's disease in Chinese population (odds ratio = 2.35, 95% confidence interval: 1.40-3.96). There is no significant association between clusterin rs11136000 with late-onset sporadic AD in our small cohort. However, meta-analysis revealed significant allele and genotype differences between Alzheimer's disease and controls following a recessive model.
CONCLUSION: Clusterin (rs11136000) was associated with Alzheimer's disease in Chinese Han population.

PMID 22296908  Am J Alzheimers Dis Other Demen. 2011 Dec;26(8):627-30.・・・
著者: C Holmes, N Cairns, P Lantos, A Mann
雑誌名: Br J Psychiatry. 1999 Jan;174:45-50.
Abstract/Text BACKGROUND: Following the success of the NINCDS-ADRDA criteria for Alzheimer's disease, groups interested in vascular dementia and dementia with Lewy bodies have now adopted similar criteria.
AIMS: To assess whether the validity of these criteria are influenced by the prevalence of mixed pathologies or by the prevalence rate.
METHOD: A community based post-mortem study.
RESULTS: Mixed pathologies were common (33.8%). The high specificities obtained for the CDLB and NINDS-AIREN criteria (1.00 and 0.95, respectively) were associated with low sensitivities (0.22 and 0.43, respectively). Low prevalence and the presence of mixed pathologies had a deleterious effect on positive predictive values.
CONCLUSIONS: Current clinical diagnostic criteria are good at detecting pathology per se but not at detecting pure pathology. A large proportion of subjects from the general population fulfilling probable CDLB, probable NINCDS-ADRDA or probable NINDS-AIREN will have mixed pathologies.

PMID 10211150  Br J Psychiatry. 1999 Jan;174:45-50.
著者: David S Knopman, Bradley F Boeve, Joseph E Parisi, Dennis W Dickson, Glenn E Smith, Robert J Ivnik, Keith A Josephs, Ronald C Petersen
雑誌名: Ann Neurol. 2005 Apr;57(4):480-8. doi: 10.1002/ana.20425.
Abstract/Text The objective of this article is to study the accuracy of antemortem clinical diagnoses of frontotemporal lobar degenerations (FTLDs). From brain autopsies performed on subjects enrolled in the Mayo Alzheimer Center between 1991 and 2003, cases with neuropathological diagnoses of FTLD were identified. Neuropathological diagnoses of FTLDs were based on consensus criteria for FTLD. The initial clinical histories, neuropsychological test results, brain imaging studies, and initial clinical diagnoses were reviewed. There were 34 pathological FTLD cases among 433 subjects who underwent autopsy; 29 of these 34 cases were diagnosed as FTLD antemortem based on the sum of clinical, neuropsychological, and imaging features (sensitivity, 85%). The specificity was 99%. Among the 34 cases with pathological FTLD, 27 (79%) had clinical histories diagnostic of an FTLD syndrome, 20 (62%) had neuropsychological profiles consistent with FTLD, 17 (50%) had magnetic resonance scans consistent with FTLD, and 7 of 8 who had functional imaging studies had ones consistent with FTLD. In those with incorrect antemortem diagnoses, three were thought to have Alzheimer's disease, one was considered hard to classify, and one was diagnosed with vascular dementia. The antemortem consensus diagnosis of FTLD was moderately sensitive and very specific. With experienced clinicians and awareness of the unique manifestations of FTLD, accurate antemortem diagnosis was feasible.

PMID 15786453  Ann Neurol. 2005 Apr;57(4):480-8. doi: 10.1002/ana.2042・・・
著者: A R Varma, J S Snowden, J J Lloyd, P R Talbot, D M Mann, D Neary
雑誌名: J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):184-8.
Abstract/Text OBJECTIVES: The diagnosis of Alzheimer's disease (AD) is now reliant on the use of NINCDS-ADRDA criteria. Other diseases causing dementia are being increasingly recognised--for example, frontotemporal dementia (FTD). Historically, these disorders have not been clearly demarcated from AD. This study assesses the capability of the NINCDS-ADRDA criteria to accurately distinguish AD from FTD in a series of pathologically proved cases.
METHODS: The case records of 56 patients (30 with AD, 26 with FTD) who had undergone neuropsychological evaluation, brain imaging, and ultimately postmortem, were assessed in terms of whether at initial diagnosis the NINCDS-ADRDA criteria were successful in diagnosing those patients who had AD and excluding those who did not.
RESULTS: (1) The overall sensitivity of the NINCDS-ADRDA criteria in diagnosing "probable" AD from 56 patients with cortical dementia (AD and FTD) was 0.93. However, the specificity was only 0.23; most patients with FTD also fulfilled NINCDS-ADRDA criteria for AD. (2) Cognitive deficits in the realms of orientation and praxis significantly increased the odds of a patient having AD compared with FTD, whereas deficits in problem solving significantly decreased the odds. Neuropsychological impairments in the domains of attention, language, perception, and memory as defined in the NINCDS-ADRDA statement did not contribute to the clinical differentiation of AD and FTD.
CONCLUSION: NINCDS-ADRDA criteria fail accurately to differentiate AD from FTD. Suggestions to improve the diagnostic specificity of the current criteria are made.

PMID 10071097  J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):184-8.
著者: G Gold, P Giannakopoulos, C Montes-Paixao Júnior, F R Herrmann, R Mulligan, J P Michel, C Bouras
雑誌名: Neurology. 1997 Sep;49(3):690-4.
Abstract/Text The objective of this study was to determine the sensitivity and specificity of clinical criteria for possible vascular dementia (VaD) recently developed independently by two groups: the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the National Institute for Neurological Disorders and Stroke with the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN). We also wished to compare the performance of the new criteria to that of the Hachinski Ischemic Score (HIS). The study was comprised of a retrospective chart review and clinicopathologic correlation, and took place in 304-bed acute-care geriatric hospital. The subjects were 113 autopsied elderly patients with dementia, who were assessed to determine sensitivity and specificity of the ADDTC and NINDS-AIREN criteria for possible VaD. Sensitivity and specificity were calculated using the neuropathologic diagnosis as a gold standard. Sensitivity was 0.63, and specificity was 0.64 for the ADDTC, 0.58 sensitivity and 0.80 specificity for the NINDS, and 0.43 sensitivity and 0.88 specificity for the HIS. Test combinations did not lead to substantial gains in sensitivity or specificity. The majority of patients with Alzheimer's disease were successfully excluded by the ADDTC (87%), the NINDS-AIREN (91%), and the HIS (97%). The proportion of mixed dementia cases clinically misclassified as VaD was 54% for the ADDTC, 29% for the NINDS-AIREN, and 18% for the HIS. Low sensitivity is the main weakness of the above clinical criteria for possible VaD. Mixed dementia is better excluded by the NINDS-AIREN than the ADDTC. Data from this validation study should provide valuable information to clinicians and researchers who wish to apply these criteria to the diagnosis of VaD.

PMID 9305324  Neurology. 1997 Sep;49(3):690-4.
著者: J T Moroney, E Bagiella, D W Desmond, V C Hachinski, P K Mölsä, L Gustafson, A Brun, P Fischer, T Erkinjuntti, W Rosen, M C Paik, T K Tatemichi
雑誌名: Neurology. 1997 Oct;49(4):1096-105.
Abstract/Text Our objectives were to investigate the utility of the Hachinski Ischemic Score (HIS) in differentiating patients with pathologically verified Alzheimer's disease (AD), multi-infarct dementia (MID), and "mixed" (AD plus cerebrovascular disease) dementia, and to identify the specific items of the HIS that best discriminate those dementia subtypes. Investigators from six sites participated in a meta-analysis by contributing original clinical data, HIS, and pathologic diagnoses on 312 patients with dementia (AD, 191; MID, 80; and mixed, 41). Sensitivity and specificity of the HIS were calculated based on varied cutoffs using receiver-operator characteristic curves. Logistic regression analyses were performed to compare each pair of diagnostic groups to obtain the odds ratio (OR) for each HIS item. The mean HIS (+/- SD) was 5.4 +/- 4.5 and differed significantly among the groups (AD, 3.1 +/- 2.5; MID, 10.5 +/- 4.1; mixed, 7.7 +/- 4.3). Receiver-operator characteristic curves showed that the best cutoff was < or = 4 for AD and > or = 7 for MID, as originally proposed, with a sensitivity of 89.0% and a specificity of 89.3%. For the comparison of MID versus mixed the sensitivity was 93.1% and the specificity was 17.2%, whereas for AD versus mixed the sensitivity was 83.8% and the specificity was 29.4%. HIS items distinguishing MID from AD were stepwise deterioration (OR, 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke (OR, 4.30), and focal neurologic symptoms (OR, 4.40). Only stepwise deterioration (OR, 3.97) and emotional incontinence (OR, 3.39) distinguished MID from mixed, and only fluctuating course (OR, 0.20) and history of stroke (OR, 0.08) distinguished AD from mixed. Our findings suggest that the HIS performed well in the differentiation between AD and MID, the purpose for which it was originally designed, but that the clinical diagnosis of mixed dementia remains difficult. Further prospective studies of the HIS should include additional clinical and neuroimaging variables to permit objective refinement of the scale and improve its ability to identify patients with mixed dementia.

PMID 9339696  Neurology. 1997 Oct;49(4):1096-105.
著者: Leonel Tadao Takada, Paulo Caramelli, Marcia Radanovic, Renato Anghinah, Ana Paula B J Hartmann, Carla Cristina Guariglia, Valéria Santoro Bahia, Ricardo Nitrini
雑誌名: Arq Neuropsiquiatr. 2003 Dec;61(4):925-9. Epub 2004 Jan 6.
Abstract/Text The importance of investigating the etiology for dementia lies in the possibility of treating potentially reversible dementias. The aims of this retrospective study are to determine the prevalence of potentially reversible dementias among 454 outpatients seen at the Cognitive and Behavioral Neurology Unit, Hospital das Clínicas, São Paulo University School of Medicine-Brazil, between the years of 1991 and 2001, and observe their evolution in follow-up. Among the initial 454 patients, 275 fulfilled the DSM-IV criteria for dementia. Alzheimer's disease was the most frequent diagnosis (164 cases; 59.6%). Twenty-two cases (8.0%) of potentially reversible dementia were observed, the most frequent diagnoses being neurosyphilis (nine cases) and hydrocephalus (six cases). Full recovery was observed in two patients and partial recovery in 10 patients. Two cases were not treated and eight cases were lost on follow-up. The prevalence found in the present study falls within the range reported in previous studies (0-30%).

PMID 14762592  Arq Neuropsiquiatr. 2003 Dec;61(4):925-9. Epub 2004 Jan・・・
著者: E Antunez, R Estruch, C Cardenal, J M Nicolas, J Fernandez-Sola, A Urbano-Marquez
雑誌名: AJR Am J Roentgenol. 1998 Oct;171(4):1131-7. doi: 10.2214/ajr.171.4.9763009.
Abstract/Text OBJECTIVE: In this study, we analyzed the sensitivity and specificity of CT and MR imaging in the diagnosis of acute Wernicke's's encephalopathy.
SUBJECTS AND METHODS: Three groups of subjects were studied: 15 patients with acute Wernicke's encephalopathy; 15 asymptomatic alcoholics; and 15 control subjects. Studies included clinical and laboratory examinations as well as CT and MR imaging of the brain.
RESULTS: On CT scans, two patients with Wernicke's encephalopathy (13%) and no asymptomatic alcoholics showed low-density abnormalities in the paraventricular regions of the thalamus (p = .2414). On MR imaging, increased T2 signal of paraventricular regions of the thalamus was observed in seven patients (46%) with Wernicke's encephalopathy and one asymptomatic alcoholic (6%) (p < .01), and increased T2 signal of periaqueductal regions of the midbrain in six patients (40%) with Wernicke's encephalopathy and one asymptomatic alcoholic (6%) (p < .05). However, no significant differences were observed in the prevalence of mamillary body shrinkage between alcoholics with Wernicke's encephalopathy (six [40%]) and asymptomatic chronic alcoholics (four [27%]). The sensitivity of MR imaging in revealing evidence of this disease was 53% and the specificity, 93%.
CONCLUSION: MR imaging is useful in confirming the diagnosis of acute Wernicke's encephalopathy. However, the absence of abnormalities on MR imaging does not exclude this diagnosis. CT proved not useful in the diagnosis of Wernicke's encephalopathy.

PMID 9763009  AJR Am J Roentgenol. 1998 Oct;171(4):1131-7. doi: 10.22・・・
著者: K S Frederiksen, C Cooper, G B Frisoni, L Frölich, J Georges, M G Kramberger, C Nilsson, P Passmore, L Mantoan Ritter, D Religa, R Schmidt, E Stefanova, A Verdelho, M Vandenbulcke, B Winblad, G Waldemar
雑誌名: Eur J Neurol. 2020 Oct;27(10):1805-1820. doi: 10.1111/ene.14412. Epub 2020 Jul 26.
Abstract/Text BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia.
METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated.
RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement).
CONCLUSION: This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.

© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
PMID 32713125  Eur J Neurol. 2020 Oct;27(10):1805-1820. doi: 10.1111/e・・・
著者: Jenny McCleery, Ann L Sharpley
雑誌名: Cochrane Database Syst Rev. 2020 Nov 15;11:CD009178. doi: 10.1002/14651858.CD009178.pub4. Epub 2020 Nov 15.
Abstract/Text BACKGROUND: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant carer distress, increased healthcare costs, and institutionalisation. Although non-drug interventions are recommended as the first-line approach to managing these problems, drug treatment is often sought and used. However, there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this clinically vulnerable population.
OBJECTIVES: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia.
SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 19 February 2020, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, and sundowning.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, risk of bias, and results. We used the mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CI) as the measures of treatment effect, and where possible, synthesised results using a fixed-effect model. Key outcomes to be included in our summary tables were chosen with the help of a panel of carers. We used GRADE methods to rate the certainty of the evidence.
MAIN RESULTS: We found nine eligible RCTs investigating: melatonin (5 studies, n = 222, five studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), the sedative antidepressant trazodone (1 study, n = 30), the melatonin-receptor agonist ramelteon (1 study, n = 74, no peer-reviewed publication), and the orexin antagonists suvorexant and lemborexant (2 studies, n = 323). Participants in the trazodone study and most participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study and the orexin antagonist studies had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. Primary sleep outcomes were measured using actigraphy or polysomnography. In one study, melatonin treatment was combined with light therapy. Only four studies systematically assessed adverse effects. Overall, we considered the studies to be at low or unclear risk of bias. We found low-certainty evidence that melatonin doses up to 10 mg may have little or no effect on any major sleep outcome over eight to 10 weeks in people with AD and sleep disturbances. We could synthesise data for two of our primary sleep outcomes: total nocturnal sleep time (TNST) (MD 10.68 minutes, 95% CI -16.22 to 37.59; 2 studies, n = 184), and the ratio of day-time to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; 2 studies; n = 184). From single studies, we found no evidence of an effect of melatonin on sleep efficiency, time awake after sleep onset, number of night-time awakenings, or mean duration of sleep bouts. There were no serious adverse effects of melatonin reported. We found low-certainty evidence that trazodone 50 mg for two weeks may improve TNST (MD 42.46 minutes, 95% CI 0.9 to 84.0; 1 study, n = 30), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; 1 study, n = 30) in people with moderate-to-severe AD. The effect on time awake after sleep onset was uncertain due to very serious imprecision (MD -20.41 minutes, 95% CI -60.4 to 19.6; 1 study, n = 30). There may be little or no effect on number of night-time awakenings (MD -3.71, 95% CI -8.2 to 0.8; 1 study, n = 30) or time asleep in the day (MD 5.12 minutes, 95% CI -28.2 to 38.4). There were no serious adverse effects of trazodone reported. The small (n = 74), phase 2 trial investigating ramelteon 8 mg was reported only in summary form on the sponsor's website. We considered the certainty of the evidence to be low. There was no evidence of any important effect of ramelteon on any nocturnal sleep outcomes. There were no serious adverse effects. We found moderate-certainty evidence that an orexin antagonist taken for four weeks by people with mild-to-moderate AD probably increases TNST (MD 28.2 minutes, 95% CI 11.1 to 45.3; 1 study, n = 274) and decreases time awake after sleep onset (MD -15.7 minutes, 95% CI -28.1 to -3.3: 1 study, n = 274) but has little or no effect on number of awakenings (MD 0.0, 95% CI -0.5 to 0.5; 1 study, n = 274). It may be associated with a small increase in sleep efficiency (MD 4.26%, 95% CI 1.26 to 7.26; 2 studies, n = 312), has no clear effect on sleep latency (MD -12.1 minutes, 95% CI -25.9 to 1.7; 1 study, n = 274), and may have little or no effect on the mean duration of sleep bouts (MD -2.42 minutes, 95% CI -5.53 to 0.7; 1 study, n = 38). Adverse events were probably no more common among participants taking orexin antagonists than those taking placebo (RR 1.29, 95% CI 0.83 to 1.99; 2 studies, n = 323).
AUTHORS' CONCLUSIONS: We discovered a distinct lack of evidence to guide decisions about drug treatment of sleep problems in dementia. In particular, we found no RCTs of many widely prescribed drugs, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks for these common treatments. We found no evidence for beneficial effects of melatonin (up to 10 mg) or a melatonin receptor agonist. There was evidence of some beneficial effects on sleep outcomes from trazodone and orexin antagonists and no evidence of harmful effects in these small trials, although larger trials in a broader range of participants are needed to allow more definitive conclusions to be reached. Systematic assessment of adverse effects in future trials is essential.

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PMID 33189083  Cochrane Database Syst Rev. 2020 Nov 15;11:CD009178. do・・・
著者: Willy Gomm, Klaus von Holt, Friederike Thomé, Karl Broich, Wolfgang Maier, Anne Fink, Gabriele Doblhammer, Britta Haenisch
雑誌名: JAMA Neurol. 2016 Apr;73(4):410-6. doi: 10.1001/jamaneurol.2015.4791.
Abstract/Text IMPORTANCE: Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.
OBJECTIVE: To examine the association between the use of PPIs and the risk of incident dementia in the elderly.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.
EXPOSURES: Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.
MAIN OUTCOMES AND MEASURES: The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.
RESULTS: A total of 73,679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70,729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).
CONCLUSIONS AND RELEVANCE: The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.

PMID 26882076  JAMA Neurol. 2016 Apr;73(4):410-6. doi: 10.1001/jamaneu・・・
著者: Ramon Mocellin, Mark Walterfang, Dennis Velakoulis
雑誌名: CNS Drugs. 2007;21(10):799-811.
Abstract/Text Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.

PMID 17850170  CNS Drugs. 2007;21(10):799-811.
著者: Ji Y Chong, Lewis P Rowland, Robert D Utiger
雑誌名: Arch Neurol. 2003 Feb;60(2):164-71.
Abstract/Text BACKGROUND: Hashimoto encephalopathy has been described as a syndrome of encephalopathy and high serum antithyroid antibody concentrations that is responsive to glucocorticoid therapy, but these could be chance associations.
OBJECTIVE: To study a patient with Hashimoto encephalopathy and to review the literature to determine whether Hashimoto encephalopathy is an identifiable syndrome.
DATA SOURCES AND EXTRACTION: We searched the MEDLINE database to June 2002 for "Hashimoto" or "autoimmune thyroiditis" and "encephalopathy" and examined all identified articles and articles referenced therein, including all languages. We included all patients with noninfectious encephalopathy (clouding of consciousness and impaired cognitive function) and high serum antithyroid antibody concentrations. We excluded patients if they did not meet these inclusion criteria or if their symptoms could be explained by another neurologic disorder. We recorded clinical features and the results of imaging, electroencephalographic, thyroid function, and cerebrospinal fluid studies.
DATA SYNTHESIS: We identified 85 patients (69 women and 16 men; mean age, 44 years) with encephalopathy and high serum antithyroid antibody concentrations. Among these patients, 23 (27%) had strokelike signs, 56 (66%) had seizures, 32 (38%) had psychosis, 66 (78%) had a high cerebrospinal fluid protein concentration, and 80 (98%) of 82 had abnormal electroencephalographic findings. Thyroid function varied from overt hypothyroidism to overt hyperthyroidism; the most common abnormality was subclinical hypothyroidism (30 patients [35%]). Among patients treated with glucocorticoids, 66 (96%) improved.
CONCLUSIONS: The combination of encephalopathy, high serum antithyroid antibody concentrations, and responsiveness to glucocorticoid therapy seems unlikely to be due to chance. However, there is no evidence of a pathogenic role for the antibodies, which are probably markers of some other autoimmune disorder affecting the brain.

PMID 12580699  Arch Neurol. 2003 Feb;60(2):164-71.
著者: M Yoneda, A Fujii, A Ito, H Yokoyama, H Nakagawa, M Kuriyama
雑誌名: J Neuroimmunol. 2007 Apr;185(1-2):195-200. doi: 10.1016/j.jneuroim.2007.01.018. Epub 2007 Mar 1.
Abstract/Text Recently, we discovered autoantibodies against the amino (NH(2))-terminal of alpha-enolase (NAE) in patients with Hashimoto's encephalopathy (HE) (83.3%; 5/6) [Fujii, A., Yoneda, M., Ito, T., Yamamura, O., Satomi, S., Higa, H., Kimura, M., Suzuki, M., Yamashita, M., Yuasa, T., Suzuki, H., Kuriyama, M., 2005. Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy. J. Neuroimmunol. 162, 130-136]. We further investigated the anti-NAE autoantibodies in 25 patients who fit the diagnostic criteria for HE, based on the presence of anti-thyroid antibodies and responsiveness to immunotherapy. In this study, we demonstrated a high prevalence (68%, 17 of 25) and high specificity of anti-NAE autoantibodies in patients with HE, and clarified the clinical features of HE. This result demonstrated that anti-NAE autoantibodies, in addition to anti-thyroid autoantibodies, are emphasized as useful serological diagnostic markers of HE.

PMID 17335908  J Neuroimmunol. 2007 Apr;185(1-2):195-200. doi: 10.1016・・・
著者: J Sone, F Tanaka, H Koike, A Inukai, M Katsuno, M Yoshida, H Watanabe, G Sobue
雑誌名: Neurology. 2011 Apr 19;76(16):1372-6. doi: 10.1212/WNL.0b013e3182166e13. Epub 2011 Mar 16.
Abstract/Text BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. Because of the variety of clinical manifestations, antemortem diagnosis of NIID is difficult.
METHODS: Seven skin biopsy samples from patients with familial NIID were evaluated histochemically, and the results were compared with those of skin samples from normal control subjects and from patients with other neurologic diseases. We also examined skin biopsy samples from patients with NIID by electron microscopy.
RESULTS: In NIID skin biopsy samples, intranuclear inclusions were observed in adipocytes, fibroblasts, and sweat gland cells. These inclusions were stained with both anti-ubiquitin and anti-SUMO1 antibodies. Electron microscopy revealed that the features of the intranuclear inclusions in adipocytes, fibroblasts, and sweat gland cells were identical to those of neuronal cells. Approximately 10% of adipocytes showed intranuclear inclusions. No intranuclear inclusions were identified in the skin samples from normal control subjects and patients with other neurologic diseases.
CONCLUSIONS: Skin biopsy is an effective and less invasive antemortem diagnostic tool for NIID.

PMID 21411744  Neurology. 2011 Apr 19;76(16):1372-6. doi: 10.1212/WNL.・・・

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