Using Functional Connectivity and the Default Network to Uncover Sex-Based Differences: Jessica Caldwell, PhD


The director of the Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic provided insight on data presented at AAIC 2022 that evaluated the interaction effect of sex and diagnosis on functional connectivity in various cognitive stages. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

Previous studies have shown that about two-thirds of people diagnosed with Alzheimer disease (AD) are women; however, the reasons for these sex disparities remain unsolved. To better understand these issues, a group of investigators explored functional connectivity of the default network (DN), one of the most important and affected networks in AD. The study compiled individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, clinically diagnosed as either healthy controls, or having mild cognitive impairment (MCI) or AD.

Led by Jessica Caldwell, PhD, the analysis used Pearson correlations to characterize functional connectivity between several regions of interest, including bilateral angular gyrus (ANG), calcarine (CAL), precuneus (PCUN), medial orbital frontal gyrus, and bilateral occipital gyrus. All told, the findings showed distinct effect sizes and/or opposite direction effects in women compared with men. Left ANG-CAL and left ANG-PCUN connectivity had medium effect (d >.05) for men in the MCI vs HC comparison, although small effect (d <.02) across sexes.

Caldwell, director of the Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic, discussed the findings in greater detail, along with the reasons for the study, and the most notable findings of which the clinical community should be aware. She also touched on how these new data adds to the growing knowledge of sex differences and their long-term effects on late-life cognition.

1. Cieri F, Yang Z, Kinney J, Cummings JL, Cordes D, Caldwell JK. Interaction effect of sex and diagnosis on functional connectivity within the default network in healthy controls, mild cognitive impairment, and Alzheimer disease. Presented at: 2022 Alzheimer’s Association International Conference; July 31 to August 4; San Diego, CA. 68142
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