Phenotypic and Clinical Traits That Correlate with Cognitive Impairment in Caucasian Females

Background: Dementia affects more women than men. This suggests sex steroid-dependent structural and functional differences between male and female brains. Natural and iatrogenic changes to women's reproductive health may correlate with risk for dementia. Objective: To identify surrogate markers of key transitions within the reproductive axis that could correlate with dementia pathology in women. Specific Research Question: Could examination of the reproductive axis from birth to senescence expand our understanding of the gender predominance of dementia in women? Proxy measurements for fetal origins, reproduction, and age-related effects on estrogen-dependent tissues were collected to study dementia risk in women. Methods: Deidentified data were collected from 289 older Caucasian female patients from an out-patient clinic in Kansas City, Missouri. Women patients 65 years and older were offered the opportunity to join the study and written consent was obtained from all participants. Data were collected from 2017 to 2019. Results: Our subjects ranged in age from 65 to 98 years old, with a mean of 76 years old. Spearman correlation analysis showed significant correlation between dementia status and age (r = 0.219, p = 0.000), Fitzpatrick skin phototype (r = -0.141, p = 0.019), birth order (r = 0.151, p = 0.028), current height as measured in the office (r = -0.215, p = 0.001), and maximum height per patient recall (r = -0.173, p = 0.005). Results from the logistic regression model show that specific predictors of risk for dementia were age (odds ratio [OR] = 1.082 [1.034-1.132]; p = 0.0007), Fitzpatrick skin phototype 1 versus 3 (OR = 8.508 [1.075-67.313]; p = 0.0227), and current height (OR = 0.766 [0.642-0.915]; p = 0.0032). Of the four variables related to fetal origins: maternal age, number of siblings, birth order, and age difference between the subject and the next older sibling, none were found to be statistically significant. Since age is a significant predictor of risk for dementia, it was included as a covariate in the aforementioned logistic regression models. Conclusions: Our results showed that dementia in Caucasian women was associated with age, lower Fitzpatrick phototype, and current height. Dementia-related pathological processes in the brain may accrue over a woman's lifetime.