Sex Differences in Clinical Risk Factors for Alzheimer's Dementia Patients with Early-Onset and Late-Onset

Nathan Gerhard Faulstich¹Sammy Hilmi Omar¹Connor John O-Brien¹Taiwo Dami¹Philip Cole Brewer¹Emmanuel I Nathaniel²Rich Goodwin³Laurie Theriot Roley⁴Thomas I Nathaniel^3*Adebobola Imeh-Nathaniel²

• ¹School of Medicine Greenville, University of South Carolina, Greenville, South Carolina, United States
• ²North Greenville University, Tigerville, South Carolina, United States
• ³University of South Carolina, Columbia, United States
• ⁴Prisma Health, Greer, South Carolina, United States

Background. The objective of this study is to identify the risk factors that contribute to sex differences in patients with Alzheimer dementia (AD), focusing on Early-Onset Alzheimer's Dementia (EAOD) and Late-Onset Alzheimer Dementia (LOAD). Additionally, the study aims to determine whether these risk factors differ between male and female EAOD and LOAD patients.Our retrospective cohort study included a total of 6,212 patients diagnosed with either EOAD or LOAD from February 2016 to August 2020. Among this population, 687 patients (11.06%) were diagnosed with EOAD, while 5,525 patients (88.94%) had LOAD. We conducted a univariate analysis to identify differences in risk factors between male and female AD patients. A multivariate analysis was also performed to predict specific risk factors associated with male and female EOAD and LOAD patients.In the adjusted analysis, males with LOAD were found to have significantly higher odds of several comorbidities, including dyslipidemia (Odds Ratio [OR] = 1.720, 95% Confidence Interval [CI] = 1.489-1.987, p < 0.001), and pneumonia (OR = 1.235, 95% CI = 1.004-1.520, p = 0.046). In contrast, females with LOAD were associated with lower odds of having hypertension (OR = 0.715, 95% CI = 0.623-0.820, p < 0.001), osteoporosis (OR = 0.310, 95% CI = 0.254-0.380, p < 0.001), and rheumatoid arthritis. In male patients with EAOD the analysis indicated a strong association with gait dysfunction (OR = 10.797, 95% CI = 3.257-35.792, p < 0.001), peripheral vascular disease (OR = 3.835, 95% CI = 1.767-8.321, p < 0.001), and Chronic Obstructive Pulmonary Disease (COPD) (OR = 5.984, 95% CI = 2.186-16.381, p < 0.001). Conversely, females with EOAD were associated with significantly lower odds of experiencing cerebrovascular accidents (OR = 0.347, 95% CI = 0.155-0.778, p < 0.001), osteoporosis (OR = 0.345, 95% CI = 0.155-0.778, p = 0.030), and anxiety (OR = 0.412, 95% CI = 0.203-0.833, p = 0.014). Our findings indicate sex differences in the risk factors for EAOD and LOAD patients. Understanding these risk factors can help us develop strategies to improve diagnostic accuracy, create targeted interventions, and enhance clinical outcomes for male and female EAOD and LOAD patients.