In a study of individuals aged 90 and older, researchers found common vascular risk factors like hypertension, diabetes, and hyperlipidemia were not associated with cerebrovascular pathologic changes, challenging long-held assumptions about brain health in advanced age.
The research, published in Alzheimer’s & Dementia, examined 267 participants with a mean age of 98 years from The 90+ Study, analyzing their brain tissue after death to understand relationships between vascular risk factors and cerebrovascular pathology. The study represents one of the largest prospective autopsy cohorts of individuals aged 90 and older.
"Our findings suggest that vascular risk factors are not risk factors for cerebrovascular pathologic changes at this age, medications have mitigated risks, or survival bias obscures associations," wrote lead author Ravi Rajmohan, MD, of the Department of Neurology at the University of California, Irvine.
The study found that 55% of participants had moderate/severe arteriolosclerosis, 40% had moderate/severe cerebral amyloid angiopathy (CAA), 30% had moderate/severe atherosclerosis, and 27% had microvascular lesions. However, these changes showed little correlation with traditional risk factors. Trends suggested that hypertension onset between ages 80 to 89 was linked to higher odds of atherosclerosis, though not statistically significant for other outcomes.
Medication adherence was notably high: 98% for those with congestive heart failure, 93% for hypertensive participants, and 63% for those with hyperlipidemia. This high compliance rate suggests effective treatment might mitigate vascular risks in advanced age. Notably, NSAID use was associated with increased odds of arteriolosclerosis and atherosclerosis, while diuretics, beta-blockers, and vasodilators showed protective effects.
The research also revealed that the APOE-ε4 gene variant was associated with a higher likelihood of CAA, particularly in those with dementia. This underscores a stronger role for genetic factors over traditional vascular risks in the oldest-old. Conversely, congestive heart failure and diabetes were linked to lower odds of microvascular lesions and CAA, respectively, possibly reflecting medication effects.
The study highlights potential gaps in understanding vascular risk management in this population. The authors propose alternative mechanisms—such as lipid metabolism and hemodynamic stability—that may be more relevant for preventing cerebrovascular changes in advanced age. They also note limitations, including reliance on self-reported data, a predominantly Caucasian and high-socioeconomic sample, and potential survival bias that could obscure associations between risk factors and pathology.
The research was supported by the National Institute on Aging and the Alzheimer's Disease Research Consortium.
The authors declared no conflicts of interest.
