IC-P3-184: Lobar gray and white matter atrophy in Alzheimer's disease: Preliminary results from the ADNI public database

Abstract

age-related brain changes in healthy adults although this has never been assessed in AD. Objective: Thus, we investigated the relationship of cardiorespiratory fitness with regional brain atrophy using Voxel Based Morphometry (VBM) and the role of APOE4 genotype in modulating this relationship. Methods: Nondemented (n 56) and early-stage AD subjects (n 63) aged 60 and over had MRI and fitness assessments. Peak oxygen consumption (VO2peak) was assessed during a symptom-limited graded treadmill test. MPRAGE images were processed using the VBM5 toolbox (http://dbm.neuro.uni-jena.de), and SPM5 algorithms (Wellcome Department of Cognitive Neurology, London, UK) including the Hidden Markov Field model (HMRF), producing modulated, smoothed (10mm) gray (GMV) and white matter (WMV) maps for analyses. First, nondemented and AD subjects were compared to identify areas of AD-related atrophy (p .05, family-wise error (FWE) corrected) and create atrophy masks (i.e., “disease regions”). Next, we regressed VO2peak across WMV and GMV within groups. Results were masked with “disease regions” to assess for fitness-related preservation of brain volume in areas most affected by AD-related atrophy. Finally, we analyzed a groupxAPOE4 interaction to look for differential fitness-brain relationships in APOE4 carriers and noncarriers (p .001 uncorrected, exploratory). All analyses were covaried for age, gender, education and whole brain volume. Results: As expected, AD-related atrophy was present in the hippocampus, temporal cortex, and parietal cortices. In “disease regions”, VO2peak in early AD subjects was significantly positively associated with WMV in the hippocampus (p 0.02), inferior temporal gyrus (p 0.038), and precentral gyrus (p 0.047). Positive trends existed in AD subjects relating GMV with VO2peak in whole-brain analyses in the superior and inferior temporal, prefrontal, and parietal cortices. A significant interaction for groupxAPOE4 genotype was present in the bilateral middle temporal cortices. APOE4 noncarriers had a stronger fitness-brain volume relationship than APOE4 carriers. Conclusions: In early-stage AD, cardiorespiratory fitness is associated with regional brain volumes in the hippocampus, temporal, and parietal cortices suggesting that maintaining cardiorespiratory fitness may positively modify AD-related brain atrophy. The presence of an APOE 4 allele may limit the positive affect of fitness on brain volume in early AD.