Associations of vascular risk and amyloid burden with subsequent dementia

Objective

Midlife vascular risk factors (MVRF) are associated with incident dementia, as are amyloid ?(A?) deposition and neurodegeneration. Whether vascular and Alzheimer Disease (AD)-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood.

Methods

Participants in the Atherosclerosis Risk in Communities (ARIC)-PET study were followed from 1987-89(45-64 yo) through 2016-17(74-94 yo), with repeat cognitive assessment and dementia adjudication. In 2011-13, dementia-free participants underwent brain MRI (with white matter hyperintensity (WMH) and brain volume measurement) and florbetapir (A?) PET. The relative contributions of vascular risk and injury (MVRF, WMH volume), elevated A? standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporo-parietal brain regions) to incident dementia were evaluated with adjusted Cox models.

Results

In 298 individuals, 36 developed dementia (median follow-up 4.9?years). Midlife hypertension and A? each independently predicted dementia risk (hypertension:HR 2.57 (95% CI 1.16-5.67); A? SUVR(per SD):HR 2.57 (1.72-3.84)), but didn’t interact significantly, whereas late-life diabetes (HR 2.50 (1.18 to 5.28)) and A? independently predicted dementia risk. WMH(per SD):HR 1.51 (1.03-2.20) and A? SUVR (HR 2.52 (1.83-3.47)) independently contributed to incident dementia but WMH lost significance when MVRF were included. Smaller temporo-parietal brain regions were associated with incident dementia, independent of A? and MVRF (HR 2.18 (1.18-4.01)).

Interpretation

Midlife hypertension and late-life A? are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia.

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