Joint Longitudinal Hazard Modeling Distinguishes Polygenic Effects on Dementia via Premorbid Cognitive Function and Aging-Related Decline

Alzheimers disease and related dementias (AD/ADRD) are clinical disorders characterized by declines in cognitive function to levels at which everyday living is meaningfully impaired. Genetic variants may confer risk for AD/ADRD by way of steeper rates of aging-related cognitive declines or their association with lower premorbid levels of cognitive function that place individuals closer to a clinically severe threshold of cognitive function. We applied joint longitudinal-hazard models to 26-year data from an ancestrally diverse US sample of N = 11,518 adults to estimate effects of multi-ancestr

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