Age, Alzheimer disease, and brain structure

Abstract

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.

Figure 1 Age-specific brain atrophy Age-specific brain atrophy projected onto the Standard Single Subject MNI template. Brain atrophy with aging is observed in all major lobes and cortices, with a relative sparing of the parietal lobes. Hotter (i.e., brighter) colors represent larger t values from the multiple regression analysis and can be interpreted as a greater magnitude of age-specific brain atrophy whereas regions in red represent smaller t values and thus a lower magnitude of atrophy.

Figure 2 Brain atrophy in Alzheimer disease (AD) Brain atrophy in the AD group is projected onto the Standard Single Subject MNI template in this figure. AD atrophy is seen most impressively in the medial temporal lobes but is also seen in the dorsolateral prefrontal cortex, and the junction of the temporal and parietal lobes.

Figure 3 Confluence of age and Alzheimer disease (AD) atrophy (A) Anterior and posterior volume renderings of the hippocampal body with result of the independent main effects of age and AD in the first 2 rows. The third row of renderings shows the results of the conjunction analysis of age and AD main effects. These are voxels in which there is both a significant effect of age with lower gray matter volume and AD atrophy. The letter “L” is placed directly adjacent to the left hemispheric rendering of the hippocampal body. Anterior and posterior orientations are also designated. (B) The same information for the entorhinal cortex.