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Atrophy rates accelerate in amnestic mild cognitive impairment

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.

Address correspondence and reprint requests to Dr. Clifford R. Jack Jr., Mayo Clinic, Diagnostic Radiology, 200 First Street SW, Rochester, MN 55905 jack.clifford{at}mayo.edu

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.

Abbreviations: AD = Alzheimer disease; aMCI = amnestic mild cognitive impairment; aMCI-P = subjects with aMCI who progressed to AD; aMCI-S = subjects with aMCI who did not progress; APOE = apolipoprotein E; AVLT = Auditory Verbal Learning Test; CDR = Clinical Dementia Rating; CN = cognitively normal; FLAIR = fluid attenuated inversion recovery; MMSE = Mini-Mental State Examination; TE = echo time; TR = repetition time; TIV = Total intracranial volume; WAIS-R = Wechsler Adult Intelligence Scale–Revised; WMS = Wechsler Memory Scale.

Supplemental data at www.neurology.org

Editorial, page 1728

e-Pub ahead of print on November 21, 2007, at www.neurology.org.

Supported by The National Institute on Aging-AG11378, AG16574, AG06786, and The Robert H. and Clarice Smith and Abigail Van Buren AD Research Program.

Disclosure: The authors report no conflicts of interest.

Received September 1, 2006. Accepted in final form July 10, 2007.

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