Neurology
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Published online before print October 21, 2009
(Neurology 2009, doi:10.1212/WNL.0b013e3181c3f293)
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Received June 11, 2009
Accepted September 10, 2009

Age, Alzheimer disease, and brain structure

C. A. Raji PhD*, O. L. Lopez MD, L. H. Kuller MD, O. T. Carmichael PhD, and J. T. Becker PhD

From the Departments of Pathology (C.A.R.), Radiology (C.A.R.), Neurology (O.L.L., J.T.B.), Epidemiology (L.H.K.), Psychiatry (J.T.B.), and Psychology (J.T.B.), School of Medicine and Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; and Department of Neurology (O.T.C.), University of California Davis, Davis.


* To whom correspondence should be addressed. E-mail: cyrusraji{at}gmail.com.

Background: Lack of clear understanding remains on the overlapping atrophy patterns of aging and early Alzheimer disease (AD) pathology in gray matter (GM) of the brain in vivo.

Objective: To evaluate the independent and overlapping patterns of GM atrophy in normal aging and AD.

Methods: A total of 169 cognitively normal subjects and 33 persons with probable AD enrolled in the longitudinal Cardiovascular Health Study–Cognition Study underwent 3-dimensional volumetric MRI scans. Controls remained cognitively normal for at least 5 years after their MRI scans and the probable AD subjects were relatively early in their clinical course with an average modified Mini-Mental State Examination score of 76/100. The scans were analyzed using voxel-based morphometry adjusting for total intracranial volume, gender, education, and race.

Results: With older age, GM volume was lower in the sensorimotor and heteromodal association areas in frontal, temporal, occipital, and parietal lobes, as well as in the cerebellum (false discovery rate p = 0.05). Additional atrophy was observed in the posterior hippocampus, thalamus, and middle cingulate gyrus. By contrast, atrophy was seen in subjects with AD in the anterior hippocampal/parahippocampal regions and the precuneus. Normal aging and AD overlapped in the hippocampal body and the entorhinal cortex.

Conclusion: Brain atrophy with aging was observed in supratentorial and infratentorial areas, as well in primary motor, sensory, and heteromodal association regions. Age and Alzheimer disease exert independent gray matter atrophy patterns but these effects overlapped substantially in the hippocampus and entorhinal cortex.






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