Sex and APOE differences in Alzheimer’s Disease‐On‐Ramp risk factor profiles: Are all risk factors for Alzheimer’s Disease created equal?
Year: 2023
Type: article
Abstract: Background Obesity, diabetes (T2D), hypertension (HTN), cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), end‐stage renal disease (ESRD), stroke and hyperlipidemia are known Alzheimer’s Disease (AD)‐on‐ramp risk factors. However, it remains unclear whether the risk conferred by these conditions is modified by other unmodifiable AD risk factors, such as chromosomal female sex and APOE genotype. Therefore, we conducted a retrospective study using the UK Biobank to determine the effect of AD‐on‐ramp risk factors, in combination with sex and APOEε4 carrier status. Method UK Biobank dataset consisted of 500k participants. Inclusion criteria were age older than 55 years old, no prior history of neurodegenerative disease, neurosurgery, or cancer, and enrollment with at least 3 years of follow‐up. Patients were propensity score‐matched based on age and educational level. We next conducted stepwise regression analysis to investigate the effect of AD‐on‐ramp risk factors. Sensitivity analyses were computed to evaluate the impact of medications prescribed for the risk factors on AD. Finally, we conducted sensitivity analyses on sex‐specific propensity score‐matched cohorts. Result Of the 181,865 participants who met inclusion criteria, 1,503 had AD and were 1:10‐matched to 15,030 patients without AD. In both cohorts, 56% were females and 44% were males and the AD cohort was predominantly APOEε4 carriers (62%). We found that stroke, T2D, HTN, HLP, and ESRD were associated with increased risk of AD, whereas obesity was a protective factor. When controlling by sex and genotype, the effect of APOEε4 was greater if considered with T2D and HTN respectively. Women exhibited greater OR of APOEε4, T2D, and HTN than men, and cholesterol medication protected against AD risk, especially in men. Conclusion These findings support previous reports that T2D, HTN, HLP, and ESRD are associated with increased risk of AD. We identified and ranked AD‐on‐ramp risk factors by their impact to explain variation in the AD onset, controlling by sex and genotype. In addition, we found sex‐specific protective factors, where obesity and cholesterol medication were associated with lower risk of developing AD in women and men respectively. Ongoing analyses include evaluation of the age‐dependent effect on AD risk factors, stratified by sex and APOE genotype.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.082316
Institution: University of Arizona
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390191825