Age-Based Dementia Risk Scores May Be Better Than One-Size-Fits-All

Age-dependent risk scores for incident all-cause dementia may be more beneficial than a general approach, a longitudinal study suggested.

Dementia risk scores should prioritize systolic blood pressure and diabetes at age 55; non-stroke cardiovascular disease at age 65; diabetes and stroke at ages 70 and 75; and diabetes, stroke, and use of anti-hypertensives at age 80, wrote Emer McGrath, MB, PhD, of the National University of Ireland Galway, and co-authors in Neurology.

"Dementia is a complicated disease and risk prediction scores need to be tailored to the individual," McGrath said in a statement. "Our findings support the use of age-specific risk prediction scores for dementia instead of a one-size-fits-all approach."

"These findings can help us to more accurately predict a person’s future risk of developing dementia and make individualized recommendations on lifestyle changes and risk factor control to help reduce their risk of dementia later on," she added.

The group studied participants in the Framingham Heart Study original and offspring cohorts, enrolled in 1948 and 1971, respectively, who were examined for vascular risk, stroke, and dementia every 2-4 years in follow-up. Data were available for 4,899 participants at age 55 (57.2% women, 10-year incident dementia 1.9%) and 2,386 people at age 80 (62.1% women, 10-year incident dementia 20.1%).

Participants had an evaluation including Framingham Stroke Risk Profile (FSRP) assessments 2.5 years of designated ages for midlife (age 55), late-life (ages 65 or 70), and later-life (ages 75 or 80). Risk factors were measured at ages 55, 65, 70, 75, and 80. Incident all-cause dementia was determined for the 10-year period following each age category, except for age 55, which was followed up from age 65 due to few dementia cases appearing between ages 55 and 65.

The FSRP was developed and validated for predicting 10-year stroke risk among individuals ≥55 years; its components are age, sex, systolic blood pressure, antihypertensive use, prevalent cardiovascular disease, current smoking, history of atrial fibrillation, and diabetes. McGrath and colleagues also included a polygenic risk score specifically for Alzheimer’s disease and calculated the change in the area under the curve (AUC) by adding genetic risk to their model.

After adjusting for age and sex, the analysis showed:

• Midlife risk factors—measured at age 55—associated with 10-year risk of dementia from age 65 included FSRP scores (HR 1.16 per standard deviation increment in log-transformed score, P<0.001), diabetes (HR 4.31, P<0.001)), and systolic blood pressure (HR 1.12, per 10 mm Hg increment, P=0.02).
• Late-life risk factors associated with 10-year incident dementia at age 65 included FSRP scores (HR 1.06, P=0.004), antihypertensive medication use (HR 1.66, P=0.01), diabetes (HR 1.96, P=0.02), atrial fibrillation (HR 2.30, P=0.05), and non-stroke cardiovascular disease (HR 1.95, P=004). At age 70, stroke (HR 3.61, P<0.001) also was associated with 10-year dementia risk, in addition to diabetes (HR 2.10, P<0.001), atrial fibrillation (HR 1.86, P=0.02), and non-stroke cardiovascular disease (HR 1.63, P<0.001).
• Later-life risk factors included a history of diabetes at age 75 (HR 1.64, P=0.002), atrial fibrillation (HR 1.57, P=0.02), and stroke (HR 2.05, P<0.001). At age 80, risk factors included diabetes (HR 1.40, P=0.03), atrial fibrillation (HR 1.43, P=0.02), and stroke (HR 1.63, P=0.009); antihypertensive use (HR 0.74, P=0.001) reduced risk. At ages 75 and 80, FSRP scores, systolic blood pressure, and prevalent non-stroke cardiovascular disease were no longer associated with 10-year dementia risk.

Adding the polygenic risk score at age 55 "marginally improved model discriminative performance," the authors noted (AUC increase from 0.64 to 0.69). At age 65, the genetic risk score negligibly changed AUC from 0.65 to 0.66. At age 70, the genetic score boosted AUC from 0.58 to 0.65, but at later ages, improvements were marginal.

The most important vascular predictors of future dementia were:

• At age 55: elevated systolic blood pressure (HR 1.17, P=0.006) and diabetes (HR 3.35, P=0.003).
• At age 65: non-stroke cardiovascular disease (HR 2.12, P=0.001).
• At age 70: diabetes (HR 1.97, P<0.001) and stroke (HR 2.43, P=0.006).
• At age 75: diabetes (HR 1.56, P=0.006) and stroke (HR 1.78, P=0.01).
• At age 80: diabetes (HR 1.45, P=0.02), stroke (HR 1.57, P=0.03), and anti-hypertensive use (HR 0.68, P<0.001).

The results were consistent with previous research identifying age-specific risk factors, including studies that have suggested multiple cardiovascular risk factors at midlife may increase future dementia risk.

"For every standard deviation unit increase in age 55 FSRP score (a metric of cumulative vascular risk), there was an approximate 1.2-fold increase in subsequent 10-year dementia risk from age 65," McGrath and co-authors wrote. "Our findings highlight the detrimental effects of a high midlife vascular risk factor burden on a person’s future risk of developing dementia commencing from the average age of retirement (65 years)."

"We identified some notable differences in the association of vascular risk factors with dementia between women and men," the authors noted. "The observed differences highlight a potential need for sex-specific as well as age-specific dementia risk scores. However, given the small sample sizes in our sex-stratified analyses, we caution that these results are purely exploratory in nature and require further investigation in larger cohorts," they acknowledged.

Other limitations include a predominantly White cohort, which may limit generalizability of results to other groups. Also, dementia-free survivors were included in the analysis at 5-year intervals, but those with more severe risk factors may have died between evaluations, leading to underestimation of the strength of association between vascular risk factors and dementia. Dementia was diagnosed using clinical and not biomarker-based research criteria, and there was insufficient power to analyze dementia subtypes.

This study was supported by the Health Research Board of Ireland, Alzheimer’s Association, National Heart, Lung, and Blood Institute, National Institute on Aging, and the National Institute of Neurological Disorders and Stroke.

McGrath reported no conflicts of interest.

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.