White matter hyperintensities may be an early marker for age-related cognitive decline in the ADNI cohort

Background: Previous research suggests that white matter hyperintensities, amyloid, and tau contribute to age-related cognitive decline. It remains unknown as to how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline. Methods: Cognitively normal older adult data from the Alzheimers Disease Neuroimaging Initiative were examined. Participants were included if they had no subjective cognitive decline, had baseline white matter hyperintensity, CSF AB42/40, CSF pTau181, and cognitive scores. Of the 102 participants included, only 79 had follow-up cognitive scores. Linear regressions examined the influence of white matter hyperintensities, amyloid, and tau on baseline and follow-up cognitive scores. Linear regressions also examined the association of amyloid and tau on white matter hyperintensities and between tau and amyloid. Results: Increased white matter hyperintensity load was associated with lower baseline memory (B= -0.20, p =.046), follow-up executive functioning (B= -0.32, p<.001), and follow-up ADAS-13 (B=2.69, p<.001) scores. White matter hyperintensities were not related to pTau or AB42/40. Lower AB42/40 was associated with increased pTau (p=.025). pTau was not associated with decline in any cognitive score. Lower AB42/40 was associated with lower baseline (p=.015) but not follow-up executive function. Discussion: White matter hyperintensities may be one of the earliest pathologies observed in healthy older adults that contribute to cognitive decline. The inclusion of white matter hyperintensities as an additional marker for early cognitive decline may improve our current understanding of age-related changes.