Long-term study ties midlife vascular health to later dementia risk

Dementia before age 80 is potentially preventable through early intervention on common vascular risk factors, according to research led by the Johns Hopkins Bloomberg School of Public Health. Findings suggest that up to 44% of dementia cases could be attributed to vascular risk factors, specifically hypertension, diabetes, or smoking.

As dementia rates continue to rise globally, efforts to prevent or delay onset remain constrained by an incomplete understanding of its origins. Hypertension, diabetes, and smoking are commonly implicated risk factors, likely acting through arteriosclerotic cerebral small vessel disease (CSVD).

CSVD is a catch-all term for a variety of conditions resulting from damage to small blood vessels in the brain. Narrowing, hardening, or obstruction of small blood vessels in the brain can starve brain cells of oxygen, which can damage nearby brain cells.

Early symptoms are often easily confused with, or overlap with, the normal effects of aging. Mental fog, forgotten names, misplaced objects, can occur naturally throughout a lifetime of remembering things, such that when vascular-related damage reaches the point of a dementia diagnosis, it may appear as a rapid onset, usually presenting later in life.

Attribution is further complicated by the frequent co-occurrence of vascular injury and Alzheimer’s pathology, leaving unresolved how much dementia could be prevented by controlling vascular conditions earlier in life.

In the study, “Contribution of Modifiable Midlife and Late-Life Vascular Risk Factors to Incident Dementia,” published in JAMA Neurology, researchers designed a prospective cohort analysis to estimate the proportion of dementia attributable to midlife and late-life vascular risk factors.

Analyses drew on 33 years of follow-up from over 12,000 adults across four US communities, with participant age at vascular risk measurement ranging from 45 to 74 years. Dementia incidence was tracked through standardized clinical assessments, proxy interviews, and linked medical records. Analyses were limited to self-identified Black and white participants.

Among participants with vascular risk factors measured at ages 45–54, 21.8% of dementia cases by age 80 were attributable to those risks. This proportion increased to 26.4% when measured at ages 55–64, and to 44.0% at ages 65–74. For dementia occurring after age 80, attributable fractions dropped sharply to between 2% and 8%.

Subgroup analyses revealed higher attributable risk in APOE ε4 noncarriers (up to 61.4% for those aged 65–74), Black participants (up to 52.9%), and females (up to 51.3%). APOE ε4 noncarriers are individuals who lack the gene variant with the strongest known risk factor for Alzheimer’s disease. In this lower genetic-risk group, modifiable vascular conditions such as hypertension, diabetes, and smoking accounted for a greater share of dementia risk.

The authors conclude, “Results suggest that maintaining ideal vascular health into late life could substantially reduce dementia risk before age 80 years.”

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