Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer’s Disease

Background Amyloid deposition and white matter lesions (WMLs) in Alzheimer's disease (AD) are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR) against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden. Methods Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr) in 8 cortical volumes-of- interests (VOIs). The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates. Results Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024), but not regional (r = 0.264, p = 0.223) AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004), superior medial- (r = 0.443, p = 0.034), and middle-prefrontal (r = 0.448, p = 0.032) regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019) and hippocampal volume (r = -0.469, p = 0.016) showed significant correlations while the prefrontal (r = -0.417, p = 0.043) or hippocampal volume (r = -0.422, p = 0.04) also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume. Conclusions BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD.