Key result
High mid-life 10-year ASCVD risk was significantly associated with late-life neurodegeneration (OR 6.98) and white matter hyperintensities, but not with amyloid or tau deposition.
Why the study?
The role of mid-life ASCVD risk factors in preclinical Alzheimer's disease pathophysiology remained elusive.
Is mid-life 10-year ASCVD risk associated with late-life brain biomarkers of Alzheimer's disease, neurodegeneration, and white matter hyperintensities in cognitively unimpaired older adults?
Cohort (n=135)
Is mid-life 10-year ASCVD risk associated with late-life brain biomarkers of Alzheimer's disease, neurodegeneration, and white matter hyperintensities in cognitively unimpaired older adults?
Odds Ratio: 6.98 (95% CI 2.44–19.95)
p-value: p=<0.05
Mid-life ASCVD risk is predictive of late-life neurodegeneration and white matter hyperintensities, suggesting a potential mechanism linking cardiovascular risk to cognitive vulnerability.
Mid-life ASCVD risk was associated with late-life AT(N) and WMHI; leaves open causal role in preclinical AD.
Introduction Atherosclerotic cardiovascular disease (ASCVD) risk factors in mid-life have been associated with cognitive decline and late-life dementia. However, the role of these risk factors in preclinical Alzheimer’s disease (AD) pathophysiology remains elusive. We investigated whether mid-life 10-year pooled cohort equations (PCE) based ASCVD risk is associated with late-life amyloid, tau, neurodegeneration [AT(N)] measures and white matter hyperintensities (WMHI). Methods Participants enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study between 2003-2005 (mid-life) and underwent brain MRI and PET scans in 2018-2022 (age >65 years, late-life) to detect and quantify amyloid (A, PiB-PET) and tau (T, Flortaucipir (FTP) PET) deposition, cortical thickness (N) and white matter hyperintensities (WMHIs). Mid-life PCE ASCVD risk was categorized as ; borderline (5%-7.4%), intermediate (7.5%-<15%), or high (≥15% ). Association of midlife ASCVD risk HR (5% CI) was assessed using logistic and linear regressions with A, T, or N and chi square beta coefficients for WMHI in latelife. Results Over a ∼16y follow up, in 135 participants (mean age 73y), A and T showed no significant association with mid-life ASCVD risk. Neurodegeneration had a graded association with mid-life ASCVD risk categories ( OR ASCVD high vs low risk% 6.98 [2.44-19.95]; p<0.05 ) driven by self-identified Black race and age. In a subset n=60, ASCVD risk score was also associated with WMHIs ( ( β= 0.42 ± 0.22; p=0.05) in a model adjusted for inflammation and education. Conclusions In this asymptomatic, diverse cohort, 10y ASCVD risk was predictive of late-life neurodegeneration and white matter hyperintensities but not amyloid or tau. These data suggest that ASCVD risk factors in midlife may lead to a state of vulnerability (through increased neurodegeneration and white matter hyperintensities) which may progress to cognitive decline and dementia. Further mechanistic studies are warranted to test this hypothesis. Abstract Figure
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Saeed et al. (2024) conducted a cohort in Cognitively Unimpaired Older Adults (n=135). Mid-life 10-year ASCVD risk score vs. Low ASCVD risk (<5%) was evaluated on Late-life neurodegeneration (cortical thickness) (OR 6.98, 95% CI 2.44-19.95, p=<0.05). High mid-life 10-year ASCVD risk was significantly associated with late-life neurodegeneration (OR 6.98) and white matter hyperintensities, but not with amyloid or tau deposition.
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