LOW GLUCOSE UTILIZATION AND HIGH LACTATE PRODUCTION IN THE ALZHEIMER'S DISEASE BRAIN

Abstract

Background: Age-related changes in the cerebral white matter (WM) have been demonstrated in cognitively intact elderly, and are associated with cognition. The etiology of microstructuralWMdegeneration and its relation to cerebral blood flow (CBF) and white matter hyperintensities (WMH) are uncertain.Methods: 61 cognitively intact elderly volunteers (mean age 85, CDR 0) underwent 3T MRI Q2TIPS pulsed arterial spin labeling (PASL), diffusion tensor imaging (DTI), and cognitive assessment. Voxelwise Tract-Based Spatial Statistics (TBSS) was performed. A general linear model using permutation-based nonparametric testing (FSLRANDOMIZE) examined regional associations betweenWMCBF,WMHs, and microstructural measures. WMHs and WM CBF were examined in relation to fractional anisotropy using both voxel-based and mean WMH volume and WM CBF values. Region of interest (ROI) analyses included atlas-based segmentation of the corpus callosum (CC), limited to the TBSS-derived WM skeleton, and examined CC integrity in relation to cognitive function. Analyses were corrected for partial volume effects and adjusted for age and gender. Matched pairs t-test examined differences in anterior and poster WM integrity.Results: In TBSS voxel-based analysis, associations between WM integrity and WMHs were observed in regions commonly associated with small vessel ischemic disease, along the periventricular WM tracts. WM integrity was significantly decreased in relation to lowerWMperfusion in similar regions. Findings were largely replicated when WMH and WM CBF were entered into the model as mean values, rather than voxel-wise analysis. In addition, clusters of decreased WM integrity were seen in areas of normal appearing white matter in the anterior and posterior cc and WM tracts in the frontal and parietal lobes. ROI analyses showed greater WM integrity disruption in the anterior compared with posterior CC. Anterior CC integrity was associated with performance on executive and memory function tests. Conclusions: Greater WMH and lower WM perfusion are independently associated with decreased WM integrity both within and outside of commonly observedWMlesions.Anterior> poster cc involvement may represent greater susceptibility of this region to hypoperfusion.WMCBF may serve as a potentiallymodifiable target in trials aimed at preserving cognitive function in elderly individuals, prior to cognitive impairment.