CORTICAL VARIABILITY AND ASYMMETRY IN NORMAL AGING AND ALZHEIMERS-DISEASE

The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed pattern of neuroanatomic change, difficult to distinguish clinically from dynamic alterations in normal aging. Extreme variation s in the sulcal patterns of the human cortex have made it difficult to identify diffuse and focal variations in cortical structure in neurod egenerative disease. We report the first comprehensive 3D statistical analysis of deep sulcal structure in vivo, in both normal aging and de mentia. High-resolution 3D T-1-weighted fast SPGR (spoiled GRASS) MRI volumes were acquired from 10 patients diagnosed with AD (NINCDS-ARDRA criteria; age: 71.9 +/- 10.7 years) and 10 normal subjects matched fo r age (72.9 +/- 5.6 years), gender, educational level and handedness. Scans were digitally transformed into Talairach stereotaxic space. To determine specific patterns of cortical variation in dementia patients , 3D average and probahilistic maps of primary deep sulci were develop ed for both normal and AD groups. Major sulci (including supracallosal , cingulate, marginal, parieto-occipital, anterior and posterior calca rine sulci, and Sylvian fissures) were modeled as complex systems of 3 D surfaces using a multi-resolution parametric mesh approach. Variatio ns and asymmetries in their extents, curvature, area and surface compl exity were evaluated. Three-dimensional maps of anatomic variability, structural asymmetry and local atrophy indicated severe regionally sel ective fiber loss in AD. A midsagittal area loss of 24.5% at the corpu s callosum's posterior midbody (P < 0.025) matched increases in struct ural variability in corresponding temporo-parietal projection areas. C onfidence limits on 3D cortical variation, visualized in 3D, exhibited severe increases in AD from 2 to 4 mm at the callosum to a peak SD of 19.6 mm at the posterior left Sylvian fissure. Normal Sylvian fissure asymmetries (right higher than left; P < 0.0005), mapped for the firs t time in three dimensions, were accentuated in AD (P < 0.0002), and w ere greater in AD than in controls (P < 0.05). Severe AD-related incre ases in 3D variability and asymmetry may reflect disease-related disru ption of the commissural system connecting bilateral temporal and pari etal cortical zones, regions known to be at risk of early metabolic dy sfunction, perfusion deficits and selective neuronal loss in AD.