title: Cerebrospinal fluid tau protein and periventricular white matter lesions in patients with mild cognitive impairment: implications for 2 major pathways.
abstract: BACKGROUND
  Mild cognitive impairment (MCI) may be a heterogeneous condition rather than a uniform disease entity.
  
  
  OBJECTIVE
  To develop reliable tools that aid in identifying patients at risk of developing Alzheimer disease (AD) among heterogeneous populations with MCI to maximize the benefits of emerging therapies for AD.
  
  
  METHODS
  A 2-year prospective study.
  
  
  METHODS
  Clinical follow-up in an outpatient memory clinic.
  
  
  METHODS
  Seventy-two consecutive older patients with memory complaints.
  
  
  METHODS
  Cerebrospinal fluid tau levels, severity of periventricular and deep white matter lesions, silent brain infarction on magnetic resonance imaging, plasma homocysteine levels, apolipoprotein E genotype, and other vascular risk factors were assessed at baseline.
  
  
  RESULTS
  Fifty-seven patients were diagnosed as having amnestic MCI. Forty-one patients with (AD-converted MCI group) or without (progressive MCI group) conversion to dementia and AD progressed over time, whereas the other 16 patients remained cognitively stable (stable MCI group). The stable MCI group was characterized by normal cerebrospinal fluid tau levels and a high grade of periventricular white matter lesions (PWMLs). The progressive MCI and AD-converted MCI groups had increased cerebrospinal fluid tau levels and low grades of PWMLs. A logistic regression model showed that age was significantly associated with developing PWMLs (P =.03; odds ratio, 1.15; 95% confidence interval, 1.0-1.3).
  
  
  CONCLUSIONS
  Tau-related AD pathologic conditions and possibly ischemic PWMLs represent 2 major etiologies in the development of MCI, reflecting heterogeneity in the clinical progression. Because the progressive type of MCI may be a primary target of clinical trials that aim at secondary prevention of dementia, these patients should be identified by appropriate biomarkers and neuroimaging techniques.
authors.affiliation: Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maruyama
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsui
authors.forename: Haruko
authors.initials: H
authors.lastname: Tanji
authors.forename: Miyako
authors.initials: M
authors.lastname: Nemoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Tomita
authors.forename: Mari
authors.initials: M
authors.lastname: Ootsuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Hidetada
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D003704:Dementia / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011859:Radiography; D012307:Risk Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins; D006710:Homocysteine