Baseline predictors of rates of hippocampal atrophy in mild cognitive impairment.
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.
van de Pol
L A
LA
Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands. L.vandepol@vumc.nl
van der Flier
W M
WM
Korf
E S C
ES
Fox
N C
NC
Barkhof
F
F
Scheltens
P
P
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
D053327:Apolipoprotein E4; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D005702:Galantamine