title: Baseline predictors of rates of hippocampal atrophy in mild cognitive impairment.
abstract: OBJECTIVE
  A large cohort of subjects with mild cognitive impairment (MCI) was categorized into tertiles based on hippocampal atrophy rates, as a proxy for Alzheimer-type pathology. We compared baseline clinical, neuropsychological, and MRI measures to characterize these MCI subgroups.
  
  
  METHODS
  Serial MRI data of 323 subjects with MCI (49% men; mean +/- SD age: 69 +/- 9 years), followed for 2 years in a clinical trial, were available. Baseline hippocampal and whole brain volumes (WBV) were measured, and hippocampal volume change was assessed. Baseline medial temporal lobe atrophy (MTA), white matter hyperintensities (WMH), and lacunes were rated visually. The cohort was categorized into tertiles based on hippocampal atrophy rates (absent, moderate, and severe).
  
  
  RESULTS
  Rates of hippocampal atrophy (%/year) were 0.0 +/- 0.8 in the absent, 1.7 +/- 0.4 in the moderate, and 3.6 +/- 1.0 in the severe (mean +/- SD) tertile. Older age and the APOE epsilon 4 allele were associated with higher hippocampal atrophy rates (p < 0.0001 and p = 0.015). General cognition deteriorated over the MCI groups (p < 0.0001), whereas, after adjustment for age and sex, episodic memory and executive function did not. Baseline hippocampal atrophy was associated with increasing atrophy rates (hippocampal volume: p = 0.025; MTA score: p = 0.008); in contrast, WBV, WMH, and lacunes, adjusted for age and sex, were not significantly associated with hippocampal atrophy rates.
  
  
  CONCLUSIONS
  In mild cognitive impairment (MCI), older age, poorer general cognition, hippocampal atrophy, and APOE epsilon 4 predict subsequent accelerated rates of hippocampal atrophy, suggestive of the accumulation of Alzheimer-type pathology, which may become clinically manifest in the future. These markers may improve identification of subjects with MCI at risk for Alzheimer disease.
authors.affiliation: Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands. L.vandepol@vumc.nl
authors.forename: L A
authors.initials: LA
authors.lastname: van de Pol
authors.forename: W M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: E S C
authors.initials: ES
authors.lastname: Korf
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D015415:Biomarkers / Q000032:analysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005702:Galantamine / Q000494:pharmacology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D005702:Galantamine