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

BackgroundResearch suggests that cerebral small vessel disease (CSVD), amyloid, and pTau contribute to age-related cognitive decline. It remains unknown how these factors relate to one another, nor how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline in cognitively normal older adults without subjective cognitive decline. MethodsA total of 230 subjects with CSF A{beta}42, CSF pTau181, white matter hyperintensities (WMHs) used as a proxy of CSVD and cognitive scores from the Alzheimers Disease Neuroimaging Initiative were included. Associations between each pathology and cognitive score were investigated using regression models. Furthermore, relationships between the three pathologies were also examined using regression models. ResultsAt baseline, there was an inverse association between WMH load and A{beta}42 (t=-4.20, p<.001). There was no association between WMH load and pTau (t=0.32, p=0.75), nor with A{beta}42 and pTau (t=0.51, p=.61). Correcting for age, sex and education, baseline WMH load was associated with baseline ADAS-13 scores (t=2.59, p=.01) and lower follow-up executive functioning (t= -2.84, p=.005). Baseline A{beta}42 was associated with executive function at baseline (t=3.58, p<.004) but not at follow-up (t=1.05, p=0.30), nor with ADAS-13 at baseline (t=-0.24, p0.81) or follow-up (t=0.09, p=0.93). Finally, baseline pTau was not associated with any cognitive measure at baseline or follow-up. ConclusionBoth baseline A{beta}42 and WMH load are associated with some baseline cognition scores, but only baseline WMH load is associated with follow-up executive functioning, indicating that it may be one of the earliest pathologies that contributes to future cognitive decline, in cognitively healthy older adults. Given that healthy older adults with WMH pathology exhibit declines in cognitive functioning, they may be less resilient to future pathology increasing their risk for cognitive impairment due to dementia than those without WMHs.