Arterial stiffness acts synergistically with APOE genotype and amyloid status to predict cognitive impairment in non‐demented elderly

Background Vascular disease is a known contributor to cognitive impairment in the elderly, often associated with impairments in Executive Functions. Aortic‐femoral Pulse Wave Velocity (PWV) measures have been proposed as a non‐invasive measure of vascular risk. However, the predictive value for cognitive decline and interactions with amyloid biomarkers have received limited study. Methods PWV was assessed in 129 non‐demented participants (108 cognitively normal and 21 mild cognitive impairment [MCI]) who underwent comprehensive medical and neuropsychological evaluation at the Shiley‐Marcos UCSD ADRC. PCA‐derived Domain Z‐Scores (relative to robust normal controls) were generated, representing Memory, Language, Visuospatial, Executive Functions, and Attention. Linear models examined if PWV significantly predicted each Domain Score and global cognition (the Mattis Dementia Rating Scale (DRS) total score), adjusting for age, sex, and education. In a subanalysis, history of hypertension, hypercholesterolemia, diabetes, stoke/TIA, CVD, atrial fibrillation, and current smoking status were each added to the model. Next, presence of an APOE ε4 allele was added and allowed to interact with PWV. Amyloid status was determined using CSF AB42/40 ratios in a subset of participants (n = 93), and its interaction with PWV was similarly tested. Results After adjusting for demographics, PWV predicted DRS scores (B=‐0.47, p=0.01), Memory Domain Scores (B=‐0.11, p=0.02), and Executive Domain Scores (B=‐0.10, p = 0.04, Figure 1). The pattern of results did not change when history of vascular risk factors was added to the models. When restricting to only cognitively normal participants, PWV significantly predicted only Executive Domain Scores (B=‐0.08, p = 0.03). Presence of an APOE e4 allele showed a significant interaction with PWV in predicting Memory (B=‐0.18, p=0.03, Figure 2). In the subsample with CSF data, the Memory Domain Score was predicted by the interaction of PWV with amyloid status (B = ‐0.30, p = 4.2x10‐4, Figure 3). Conclusions Arterial Stiffness measured through aortic‐femoral PWV is a predictor of cognitive impairment, especially in the Memory and Executive Function domains, and interacts with markers of Alzheimer’s disease (APOE and amyloid status), such that a stronger relationship is found in the amyloid/ε4 positive population.