Abstract
Identifying neurobiological biomarkers associated with cognitive decline, as well as potential interactions between these biomarkers, are critical for advancing treatment of the growing aging population. Using fMRI and PET brain imaging techniques, this study examined the relationship between Alzheimer’s Disease (AD) pathology, the dopaminergic system, and white matter integrity in a sample of 47 cognitively normal older adults. Processing speed was measured by three different cognitive tests in order to assess the relationship between our biomarkers of interest and cognitive decline. Examining amyloid beta volume, tau volume, dopamine (DA) synthesis capacity, and white matter hyperintensities (WMH), an indicator of white matter integrity, we did not find evidence of correlation between any of these biomarkers of interests, nor interactions between these biomarkers in predicting cognitive performance. However, we did observe independent effects of both tau and WMH in predicting processing speed, revealing white matter integrity and tau burden as critical measures of interest in understanding the underlying mechanisms of subtle age-related cognitive changes among high functioning, cognitively normal older adults. Follow up studies are needed to confirm whether these relationships hold true in subjects with AD or other forms of dementia; however, taken together with previous studies, our analyses implicate WMH and tau as key targets for intervention in detecting, preventing, and alleviating cognitive decline across the aging population.