Vascular risk is not associated with Alzheimer's disease neuropathology among cognitively normal older adults

Cardiovascular disease (CVD) is associated with a higher risk of developing dementia. Studies have found that vascular risk factors are associated with greater amyloid and tau burden, which are hallmark neuropathologies of Alzheimers disease (AD). Evidence for these associations during the preclinical stages of AD, when amyloid and tau pathologies first become detectable, is mixed. Quantifying the effect of vascular risk among cognitively normal individuals can help focus the efforts to develop therapeutic approaches aimed at modifying the course of preclinical AD. Using Bayesian analysis, we examined the relationship of amyloid and tau pathology with concurrent vascular risk among 87 cognitively normal individuals (median age 77, interquartile range 70-83) in the Baltimore Longitudinal Study of Aging. We quantified vascular risk as the probability of developing CVD within 10 years using published equations from the Framingham Heart Study. Amyloid and tau pathologies were measured using positron emission tomography. As expected, amyloid positive participants had greater tau in the entorhinal cortex (EC) and inferior temporal gyrus (ITG) (difference in means = 0.09, p < 0.05 for each region), and 10-year CVD risk was positively correlated with white matter lesion burden (r = 0.24, p = 0.03). However, we did not find any associations between CVD risk and amyloid or tau. The data provided over two- and four-fold evidence towards the lack of a correlation between CVD risk and tau in the EC (Bayes factor BF = 2.4) and ITG (BF = 4.0), respectively. We found over three-fold evidence towards the lack of a difference in mean CVD risk by amyloid group (BF = 3.4). These null findings were replicated using a data-driven vascular risk score in the BLSA based on a principal component analysis of eight indicators of vascular health. Our data provide moderate evidence towards the lack of an association between vascular risk and concurrent AD neuropathology among cognitively normal older adults. This finding suggests that vascular risk and AD neuropathology may constitute independent pathways in the development of cognitive impairment and dementia. HighlightsO_LIVascular risk is associated with white matter lesion load, but not amyloid or tau C_LIO_LIModerate evidence for lack of association between vascular risk & early AD pathology C_LIO_LIVascular risk and Alzheimers neuropathology may constitute independent pathways C_LI