Risk factors associated with developing dementia varied by age, a longitudinal analysis showed.
At age 55, diabetes (HR 3.35, P=0.003) and high systolic blood pressure (HR 1.17, P=0.006) were the most important predictors of future dementia, reported Emer McGrath, MBBCh, PhD, of National University of Ireland Galway, and co-authors in .
At 65, non-stroke cardiovascular disease (HR 2.12, P=0.001) was the most important risk factor predicting 10-year dementia. For people in their 70s, diabetes (HR 1.97, P<0.001) and stroke (HR 2.43, P=0.006) topped the list.
At 80, diabetes (HR 1.45, P=0.02), stroke history (HR 1.57, P=0.03), and antihypertensive use (HR 0.68, P<0.001) most strongly predicted 10-year dementia.
"Predicting a person's future risk of dementia likely needs to be made at an individual level, taking age, sex, vascular risk burden, and end-organ damage into account," McGrath told .
"It is likely that controlling high blood pressure, preventing diabetes mellitus, and following a healthy lifestyle could help reduce a person's risk of dementia later on," she added.
Midlife factors including obesity, physical inactivity, low education, and multimorbidity have been linked to subsequent dementia in earlier studies. In this analysis, McGrath and colleagues assessed the relationship between all-cause dementia and vascular risk factors in the Framingham Heart Study, adding a score for Alzheimer's dementia to their model.
The researchers evaluated participants in the original and offspring cohorts who had available Framingham Stroke Risk Profile () data.
The FSRP was developed and validated for predicting 10-year stroke risk in people 55 and older, McGrath and colleagues noted. "The FSRP has also been associated with brain atrophy and cognitive decline in a community-based setting," they wrote. "However, it is unknown if the FSRP is predictive of dementia risk across mid- to later-life or if the association between component vascular risk factors and incident dementia varies with age."
Risk factors were measured at five timepoints: in midlife at age 55 and again at ages 65, 70, 75, and 80. Ten-year dementia follow-up periods began at age 65. Participants were followed from the time of risk factor measurement to the time of incident dementia, death, or until the last date they were confirmed to be dementia-free.
At age 55, the study consisted of 4,899 people (57.2% women). By age 80, 2,386 dementia-free participants had data available (62.1% women).
Age- and sex-adjusted risk factors measured in midlife -- at age 55 -- that were associated with a 10-year risk of dementia from age 65 included FSRP scores, diabetes, and systolic blood pressure. Factors linked with 10-year risk in late life -- from ages 65 or 70 -- included FSRP scores, antihypertensive use, diabetes, atrial fibrillation, non-stroke cardiovascular disease, and stroke. Factors in later life -- from ages 75 or 80 -- were antihypertensive use, diabetes, atrial fibrillation, and stroke.
At most ages, adding an Alzheimer's genetic risk score only marginally improved model discrimination using area under the curve (AUC). At age 70, though, the genetic risk score raised AUC from 0.58 to 0.65.
"Our findings support the use of age-specific dementia risk scores which should prioritize including at age 55, systolic blood pressure and diabetes mellitus; age 65, non-stroke cardiovascular disease; ages 70 and 75, diabetes mellitus and stroke; and age 80, diabetes mellitus, stroke and antihypertensive use," McGrath and co-authors wrote.
The study had several limitations. The Framingham sample was predominantly Caucasian and results may not apply to other populations. Dementia-free survivors at 5-year intervals were included in the analysis but people with more severe vascular risk profiles may have died between exam periods, influencing the results. In addition, dementia was diagnosed using clinical rather than biomarker-based criteria, and dementia subtypes were not evaluated.
Disclosures
The study was supported by the Health Research Board of Ireland, the Alzheimer's Association, the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke.
The researchers reported no disclosures relevant to the manuscript.
Primary Source
Neurology
McGrath ER, et al "Determining vascular risk factors for dementia and dementia risk prediction across mid- to later-life: The Framingham Heart Study" Neurology 2022; DOI: 10.1212/WNL.0000000000200521.