Diabetes and hypertension are associated with elevated beta-amyloid burden: evidence from the prospective population-based Rotterdam Study

Background: Higher vascular risk increases the likelihood of developing dementia. Better understanding the association between vascular risk and Alzheimer’s disease (AD) pathology at the pre-dementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of vascular risk on the presence and severity of in-vivo measured brain beta-amyloid (Aβ) plaques in participants from the population-based Rotterdam Study. Methods: Vascular risk factors (hypertension, hypercholesterolemia, diabetes, obesity, physical inactivity, and smoking) were assessed twelve and seven years prior to ¹⁸F-florbetaben positron emission tomography (PET) in 506 dementia-free participants. Vascualr risk factors were associated with binary amyloid PET status or continuous PET readouts (SUVr values) using logistic and linear regression models respectively, adjusted for age, sex, education, APOE4 risk allele count, and time between vascular risk and PET assessment. Results: Participants’ mean age at time of amyloid PET was 68 years (range: 60-90), 262 (51.8%) were women and 158 (31.2%) carried at least one APOE4 risk allele (Figure 1). The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age (12% in 60-69y vs. 45.5% in 80-89y age-groups) and APOE4 allele count (8.3% in non-carriers vs. 34.8 to 58.8% in carriers of one or two risk allele(s); Figure 2). A diagnosis of diabetes seven years prior to PET assessment was associated with a higher risk of a positive amyloid status (OR[95%CI]=4.07[1.66–9.71], P=0.002; Figure 3) and higher SUVr values, indicating more severe Aβ pathology (standardized beta=0.478[0.205–0.750], P=0.001; Figure 4). We found evidence for an association between hypertension and higher SUVr values in APOE4 carriers, but not in non-carriers (interaction: standardized beta=0.425[0.092–0.758], P=0.013; Figure 5). Hypercholesterolemia, obesity, physical inactivity and smoking were not related to amyloid PET measures. Conclusion: The current findings suggest a contribution of diabetes and hypertension to the pathophysiology of AD. Since both conditions respond well to lifestyle modification and drug treatment, further research should be conducted to examine the preventative effect of early risk management on the development of AD neuropathology.