Sex Differences in Comorbidity Patterns and the Associations with Risk of Alzheimer’s Disease and AD‐Related Dementias among Adults Aged 65 and Older: Findings from the United States Medicare Current Beneficiaries Surveys, 2018‐2020

Abstract Background To provide a nationally representative estimate of the burden of multiple comorbidities (MCM) among community‐dwelling Medicare beneficiaries with Alzheimer’s disease (AD) and AD related dementias (ADRD). Method We analyzed national sampling data in Medicare beneficiaries aged ≥65 (n = 34,318) from the 2018‐2020 Medicare Current Beneficiaries Surveys. AD/ADRD and twelve chronic comorbidities (hypercholesterolemia, hypertension, diabetes, coronary heart disease, heart failure, stroke, depression, mental disorder, chronic kidney disease, chronic obstructive pulmonary disease, arthritis, and osteoporosis) were examined. A novel age‐adjusted regression weighted MCM index was developed by taking into account the relative impact of each comorbidity on the risk of AD/ADRD. Logistic regression models estimated adjusted odds ratios (AORs) of commodity and the MCM index for AD/ADRD, adjusting for sociodemographic, body mass index and behavior factors. Result A total of 1,802 AD/ADRD cases (5.3%) were identified, representing an estimated 5,580,421 AD/ADRD cases in the nation’s Medicare beneficiaries. In the 65‐74 age group, the prevalence of AD/ADRD was 1.8% in males and 1.4% in female (p = 0.11), while in those aged ≥75, it was 6.1% in males and 7.6% in females (p = 0.001). AD/ADRD individuals more often had ≥4 comorbidities than those without AD/ADRD (52.6% vs. 30.9% in males, and 58.3% vs. 34.8% in females). In males, of the 12 comorbidities, depression exhibited the highest AOR (95%CI) at 4.62 (3.70‐5.78) for AD/ADRD risk, followed by mental disorder at 4.36 (2.88‐6.59), and stroke at 3.19 (2.51‐4.06). The same disorders were the top three in females, but in a different order, namely mental disorders at 4.79 (3.44‐6.68), stroke at 3.50 (2.79‐4.39), and depression at 2.92 (2.41‐3.54). An increase in MCM index score was associated with 2.13 (1.92‐2.37) higher AD/ADRD risk in males, and 1.65 (1.52‐1.80) higher risk in females. Conclusion The study highlights that AD/ADRD poses a substantial public health burden in the nation, with older females experiencing a significantly higher prevalence of AD/ADRD. The association of sex and specific comorbidity profiles on AD/ADRD risk is evident, emphasizing the need for further studies of the disease mechanisms and the potentially targeted prevention strategies by addressing these factors.