Our principal finding is that familial risk for AD results in reduced volume in regions that are separate from those seen in association with prenatal exposure. High-risk male subjects exhibit lower gray matter volume in the fusiform, insula and inferior temporal regions. Similarly, female HR subjects showed reduced volume for the right fusiform. These regions have been identified as important in social cognition. The fusiform is a key brain area involved in social perception and cognition and provides a building block for social skill development (Schultz, 2005). Our results are consistent with an alcohol cue-related fMRI study that found differences in BOLD response between family history positive and negative college students with greater activation of the fusiform to repeated alcohol related images in family history positive subjects relative to controls (Dager et al., 2013). Similarly, our finding of reduction in insula volume in HR males is congruent with a report showing that the insula plays a key role in the recall of emotional experience during craving and influences drug seeking decision-making (Naqvi et al., 2014). These results suggest that regions associated with social cognition may provide neural underpinnings for a genetic diathesis for familial risk for AD.
