Hypertension and Hypercholesterolemia Modify Dementia Risk in Relation to APOEɛ4 Status.

Abstract

There is significant interest in understanding the role of modifiable vascular risk factors contributing to dementia risk across age groups. Risk of dementia onset was assessed in relation to vascular risk factors of hypertension and hypercholesterolemia among cognitively normal APOEɛ4 carriers and non-carriers. In a sample of prospectively characterized longitudinal cohort from the National Alzheimer's Coordinating Center database, 9,349 participants met criteria for normal cognition at baseline, had a CDR-Global (CDR-G) score of zero, and had concomitant data on APOEɛ4 status and medical co-morbidities including histories of hypertension and hypercholesterolemia. Multivariable Cox proportional hazards models adjusted for well-known potential confounders were used to compare dementia onset among APOEɛ4 carriers and non-carriers by young (≤65 years) and old (> 65 year) age groups. 519 participants converted to dementia within an average follow up of 5.97 years. Among older APOEɛ4 carriers, hypercholesterolemia was related to lower risk of dementia (HR (95% CI), 0.68 (0.49-0.94), p = 0.02). Among older APOEɛ4 non-carriers, hypertension was related to higher risk of dementia (HR (95% CI), 1.44 (1.13-1.82), p = 0.003). These results were corroborated among a subset with autopsy data characterizing underlying neuropathology. Among younger participants, vascular risk factors did not impact dementia risk, likely from a lower frequency of vascular and Alzheimer's as etiologies of dementia among this cohort. A history of hypercholesterolemia related to a lower risk of dementia among older APOEɛ4 carriers, while hypertension related to a higher risk of dementia among older APOEɛ4 non-carriers.