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.