SEX DIFFERENCES IN ALZHEIMER’S DISEASE RISK FACTORS IN THE SOUTHERN COMMUNITY COHORT STUDY

Q: What cohort and data source were used to study sex differences in ADRD risk?

The analysis used the Southern Community Cohort Study (SCCS) with participants enrolled in Medicare, and incident ADRD was ascertained via Centers for Medicare and Medicaid Services linkage through December 2020.

Q: Which ADRD risk factors were examined?

Risk factors included education, low physical activity, high sedentary time, smoking, alcohol use, obesity, social isolation, sleep duration, and physician diagnosis of depression, hypertension, and hypocholesterolemia.

Q: How did associations between risk factors and incident ADRD differ between females and males?

Females were more likely than males to have several risk factors and, over follow-up, associations with incident ADRD were stronger among females for higher education, hypercholesterolemia, depression, higher sedentary time, hypertension, and social isolation.

Sep 28, 2026

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Aging women in the United States experience a disproportionate Alzheimer’s disease and related dementias burden, yet the drivers of this sex disparity remain unclear. Using the Southern Community Cohort Study, sex-stratified prevalence of Alzheimer’s/ADRD risk factors was analyzed and linked to incident ADRD through Medicare claims. Cox proportional hazard models adjusted for key sociodemographic variables found females more often had depression, metabolic and cardiovascular conditions, obesity, social isolation, and short sleep, with stronger associations for higher education, hypercholesterolemia, depression, sedentary time, hypertension, and social isolation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages2

Reading Time5 min

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Abstract

Study design and cohort

Risk factors assessed

Statistical methods

Main findings

1282 Innovation in Aging, 2025, Vol. 9, No. S2 Abstract citation ID: igaf122.4278 SEX DIFFERENCES IN ALZHEIMER’S DISEASE RISK FACTORS IN THE SOUTHERN COMMUNITY COHORT STUDY Kelsie Full1, Xijing Han2, Hui Shi2, Danxia Yu2, Logan Dumitrescu2, Atul Malhotra3, and Loren Lipworth2, 1. Vanderbilt University Medical Center, Nashville, Tennessee, United States, 2. Vanderbilt University Medical, Nashville, Tennessee, United States, 3. University of California, San Diego, School of Medicine, La Jolla, Florida, United States In the United States, aging women bear a disproportionate Alzheimer’s disease (AD) and related dementias (ADRD) burden, accounting for nearly 2/3 of cases. This striking sex disparity remains poorly understood and may be driven by differences in ADRD risk factors. In the Southern Community Cohort Study (SCCS), we investigated the sex-stratified prevalence of the 2024 Innovation in Aging, 2025, Vol. 9, No. S2 1283 Lancet Commission on Dementia identified ADRD risk factors and associations with incident ADRD. This analysis includes 28,250 SCCS participants (mean age: 60 years; 62% females; 59% Black) who reached ≥65 years prior to end of follow-up and were continuously enrolled in Medicare. ADRD risk factors included education, low physical activity, high sedentary time, smoking, alcohol use, obesity, social isolation, sleep duration, and physician diagnosis of depression, hypertension, and hypocholesterolemia. Incident ADRD was ascertained via Centers for Medicare and Medicaid Services linkage through December 2020. We ran Cox proportional hazard models adjusting for age, race, education, employment and income. Compared to males, females were significantly more likely to have depression, hypercholesterolemia, diabetes, hypertension, obesity, social isolation and short sleep duration (all p-values < 0.001). Over 4.5 years of follow-up, 1,994 ADRD cases occurred among females and 1,095 cases among males. Associations with incident ADRD were stronger among females compared to males for higher education (Hazard Ratios (HRs): 1.33; 1.19), hypercholesterolemia (HRs:1.10; 0.98), depression (HRs: 1.60; 1.39), higher sedentary time (HRs: 1.31; 1.18), hypertension (HRs:1.24; 1.12), and social isolation (HRs: 1.25; 1.19). ADRD risk factors that are more prevalent and impactful in females may inform novel prevention strategies.

FAQs

What cohort and data source were used to study sex differences in ADRD risk?

The analysis used the Southern Community Cohort Study (SCCS) with participants enrolled in Medicare, and incident ADRD was ascertained via Centers for Medicare and Medicaid Services linkage through December 2020.

Which ADRD risk factors were examined?

Risk factors included education, low physical activity, high sedentary time, smoking, alcohol use, obesity, social isolation, sleep duration, and physician diagnosis of depression, hypertension, and hypocholesterolemia.

How did associations between risk factors and incident ADRD differ between females and males?

Females were more likely than males to have several risk factors and, over follow-up, associations with incident ADRD were stronger among females for higher education, hypercholesterolemia, depression, higher sedentary time, hypertension, and social isolation.

Sep 28, 2026

Upload by Stanford