Amyloid deposition is associated with different patterns of hippocampal connectivity in men versus women

Compared to men, women are disproportionally affected by Alzheimer's disease (AD) and have an accelerated trajectory of cognitive decline and disease progression. Neurobiological factors underlying gender differences in AD remain unclear. This study investigated brain beta-amyloid (A beta)-related neural system differences in cognitively normal older men and women (N = 61; 41 females, 65-93 years old). We found that men and women showed different associations between A beta load and hippocampal functional connectivity. During associative memory encoding, in men greater A beta burden was accompanied by greater hippocampus-prefrontal connectivity (i.e., more synchronized activities), whereas in women hippocampal connectivity did not vary by A beta burden. For resting-state data, the interaction of gender x A beta on hippocampal connectivity did not survive multiple comparison in the whole-brain analyses. In the region of interest-based analyses, resting-state hippocampal-prefrontal connectivity was positively correlated with A beta load in men and was negatively correlated with A beta load in women. The observed A beta-related neural differences may explain the accelerated trajectory of cognitive decline and AD progression in women. (C) 2018 Elsevier Inc. All rights reserved.