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MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment

From the Departments of Radiology (J.L.W., M.M.S., C.R.J.), Biostatistics (S.A.P., S.D.W.), and Neurology (Behavioral Neurology) (D.S.K., B.F.B., R.C.P.), Mayo Clinic Rochester, MN.

Address correspondence and reprint requests to Dr. Clifford R. Jack Jr., Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 jack.clifford{at}mayo.edu

Objective: To compare the patterns of gray matter loss in subjects with amnestic mild cognitive impairment (aMCI) who progress to Alzheimer disease (AD) within a fixed clinical follow-up time vs those who remain stable.

Methods: Twenty-one subjects with aMCI were identified from the Mayo Clinic Alzheimer's research program who remained clinically stable for their entire observed clinical course (aMCI-S), where the minimum required follow-up time from MRI to last follow-up assessment was 3 years. These subjects were age- and gender-matched to 42 aMCI subjects who progressed to AD within 18 months of the MRI (aMCI-P). Each subject was then age- and gender-matched to a control subject. Voxel-based morphometry (VBM) was used to assess patterns of gray matter atrophy in the aMCI-P and aMCI-S groups compared to the control group, and compared to each other.

Results: The aMCI-P group showed bilateral loss affecting the medial and inferior temporal lobe, temporoparietal association neocortex, and frontal lobes, compared to controls. The aMCI-S group showed no regions of gray matter loss when compared to controls. When the aMCI-P and aMCI-S groups were compared directly, the aMCI-P group showed greater loss in the medial and inferior temporal lobes, the temporoparietal neocortex, posterior cingulate, precuneus, anterior cingulate, and frontal lobes than the aMCI-S group.

Conclusions: The regions of loss observed in subjects with amnestic mild cognitive impairment (aMCI) who progressed to Alzheimer disease (AD) within 18 months of the MRI are typical of subjects with AD. The lack of gray matter loss in subjects with aMCI who remained clinically stable for their entire observed clinical course is consistent with the notion that patterns of atrophy on MRI at baseline map well onto the subsequent clinical course.

GLOSSARY: AD = Alzheimer disease; ADNI = Alzheimer's Disease Neuroimaging Initiative; ADPR = Alzheimer's Disease Patient Registry; ADRC = Mayo Clinic Alzheimer's Disease Research Center; aMCI = amnestic mild cognitive impairment; APOE e4 = apolipoprotein epsilon 4; AVLT = Auditory Verbal Learning Test; CDR-SB = CDR sum of boxes; DCT = discrete cosine transformation; FDR = false discovery rate; FWHM = full-width at half-maximum; GM = gray matter; MMSE = Mini-Mental State Examination; MNI = Montreal Neurological Institute; NIA = National Institute on Aging; TIV = total intracranial volume; VBM = voxel-based morphometry; WM = white matter; WMH = white matter hyperintensity.

Editorial, page 502

e-Pub ahead of print on September 26, 2007, at www.neurology.org.

Supported by grants P50 AG16574, U01 AG06786, R01 AG11378 from the National Institute on Aging, Bethesda, MD, and the generous support of the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation, USA.

Disclosure: D.S.K. has been a consultant to GE HealthCare, GlaxoSmithKline, and Myriad Pharmaceuticals, has served on a Data Safety Monitoring Board for Neurochem Pharmaceuticals, and is an investigator in a clinical trial sponsored by Elan Pharmaceuticals. R.C.P. has been a consultant to GE Healthcare and is on a Treatment Effects Monitoring Committee for a clinical trial sponsored by Elan Pharmaceuticals. B.B. is an investigator in a clinical trial sponsored by Myriad Pharmaceuticals. C.R.J. receives research support in the form of research grants from Pfizer.

Received March 16, 2007. Accepted in final form July 2, 2007.

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