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From the Department of Radiology (C.R.J., M.M.S., J.L.G.), Division of Biostatistics (S.D.W., S.A.P., P.C.O.), Neurology (D.S.K., B.F.B., R.C.P.), and Psychiatry and Psychology (G.E.S.), Mayo Clinic and Foundation, Rochester, MN.
* To whom correspondence should be addressed. E-mail: jack.cliffor{at}@mayo.edu.
ABSTRACT
Background: We tested if rates of brain atrophy accelerate in individuals with amnestic mild cognitive impairment (aMCI) as they progress to typical late onset Alzheimer disease (AD). We included comparisons to subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN).
Methods: We studied 46 subjects with aMCI who progressed to AD (labeled aMCI-P), 46 CN, and 23 aMCI-S. All subjects must have had three or more serial MRI scans. Rates of brain shrinkage and ventricular expansion were measured across all available serial MRI scans in each subject. Change in volumes relative to the point at which subjects progressed to a clinical diagnosis of AD (the index date) was modeled in aMCI-P. Change in volumes relative to age was modeled in all three clinical groups.
Results: In aMCI-P the change in pre to post index rate (i.e., acceleration) of ventricular expansion was 1.7 cm3/year, and acceleration in brain shrinkage was 5.3 cm3/year. Brain volume declined and ventricular volume increased in all three groups with age. Volume changes decelerated with increasing age in aMCI-P, and to a lesser extent in aMCI-S, but were linear in the matched CN. Among all subjects with aMCI, rates of atrophy were greater in apolipoprotein E 
4 carriers than noncarriers.
Conclusions: Rates of atrophy accelerate as individuals progress from amnestic mild cognitive impairment (aMCI) to typical late onset Alzheimer disease (AD). Rates of atrophy are greater in younger than older subjects with aMCI who progressed to AD and subjects with aMCI who did not progress. We did not find that atrophy rates varied with age in 70- to 90-year-old cognitively normal subjects.
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