Sex Differences in White Matter Microstructure and Cognition in Healthy Aging




Ohlhauser, Lisa

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As the global population of older adults increases, it is crucial to study the healthy aging brain. Sex and gender are important determinants of health that may impact the aging trajectory, especially since women outlive men in most populations worldwide. To date, most studies examining sex and gender differences in aging have been cross-sectional and have focused on grey matter. In contrast, studies investigating age-related changes in white matter (WM) with longitudinal designs have been limited. The following three studies used available data from the healthy control group of the Parkinson Progression Markers Initiative (PPMI) to investigate biological sex differences in WM and cognition, as well as changes in these variables over time. In Study 1, sex differences in WM as measured by diffusion tensor imaging (DTI) were examined in a sample of 40 healthy older adults using tract-based spatial statistics. Results showed no significant differences in the most used DTI metrics of fractional anisotropy (FA) or mean diffusivity (MD) when controlling for total brain volume. In Study 2, longitudinal changes in WM were examined in the same healthy older adult sample over a one-year time frame. Stability in both FA and MD were found when examining changes in WM for males and females separately. Findings from Study 2 demonstrate that healthy older adult males and females showed similar stability in WM over a one-year period. In Study 3, longitudinal changes in cognition were examined in 193 healthy control participants from the PPMI. Linear mixed modeling was used to examine within-person change over time and between-person differences in cognition for up to six annual time points. Findings from Study 3 demonstrated that although males and females may have baseline differences in some cognitive domains, both sexes had similar stability in cognition over the five-year study period. Overall, these studies contribute to a growing body of literature examining sex similarities and differences in brain structure and function throughout the normal aging process. This research ultimately aids in the long-term goals of aging research to prevent disease and promote health and well-being into the latter decades of life.



sex, gender, white matter, diffusion tensor imaging, cognition, longitudinal