Cortical variability and asymmetry in normal aging and Alzheimer's disease

The onset of Alzheimer's disease (AD) is accompanied by a complex anddistributed pattern of neuroanatomic change, difficult to distinguishclinically from dynamic alterations in normal aging. Extreme variations inthe sulcal patterns of the human cortex have made it difficult to identifydiffuse and focal variations in cortical structure in neurodegenerativedisease. We report the first comprehensive 3D statistical analysis of deepsulcal structure in vivo, in both normal aging and dementia.High-resolution 3D T1-weighted fast SPGR (spoiled GRASS) MRI volumes wereacquired from 10 patients diagnosed with AD (NINCDS-ARDRA criteria; age:71.9 +/- 10.7 years) and 10 normal subjects matched for age (72.9 +/- 5.6years), gender, educational level and handedness. Scans were digitallytransformed into Talairach stereotaxic space. To determine specificpatterns of cortical variation in dementia patients, 3D average andprobabilistic maps of primary deep sulci were developed for both normal andAD groups. Major sulci (including supracallosal, cingulate, marginal,parieto-occipital, anterior and posterior calcarine sulci, and Sylvianfissures) were modeled as complex systems of 3D surfaces using amulti-resolution parametric mesh approach. Variations and asymmetries intheir extents, curvature, area and surface complexity were evaluated.Three- dimensional maps of anatomic variability, structural asymmetry andlocal atrophy indicated severe regionally selective fiber loss in AD. Amidsagittal area loss of 24.5% at the corpus callosum's posterior midbody(P < 0.025) matched increases in structural variability in correspondingtemporo-parietal projection areas. Confidence limits on 3D corticalvariation, visualized in 3D, exhibited severe increases in AD from 2 to 4mm at the callosum to a peak SD of 19.6 mm at the posterior left Sylvianfissure. Normal Sylvian fissure asymmetries (right higher than left; P <0.0005), mapped for the first time in three dimensions, were accentuated inAD (P < 0.0002), and were greater in AD than in controls (P < 0.05).Severe AD-related increases in 3D variability and asymmetry may reflectdisease-related disruption of the commissural system connecting bilateraltemporal and parietal cortical zones, regions known to be at risk of earlymetabolic dysfunction, perfusion deficits and selective neuronal loss inAD.