BACKGROUND:
Many risk factors can contribute to the occurrence of Alzheimer`s Disease (AD). However, little is known about the impact of dementia risk factors to the uptake of tau-PET tracers. Therefore, in this work we aim to investigate the influence of dementia risk factors and comorbidities on 18 F-Flortaucipir (FTP) and 18 F-MK6240 (MK) tau-PET tracers’ uptake. Additionally, we will assess how these factors impact the association of tau-PET and cognition.
METHODS:
We accessed 436 individuals across the aging and AD spectrum (251 amyloid negative and 185 amyloid positive) from the HEAD study, with available Aβ-PET, FTP, MK, and clinical assessments. Linear regression models corrected for age, sex, clinical diagnosis, and study site tested the association of factors with tau-PET tracers in the medial temporal lobe (MTL). A tau-PET × risk factor term was added to test the influence of risk factors to the association of tau with cognition.
RESULTS:
In amyloid-β negative individuals, high BMI were positively associated with the uptake of both FTP and MK, whereas hearing loss were positively associated only with MK in the MTL. In amyloid-β positive individuals, high body mass index (BMI), hearing loss and sleep disorders were negatively associated with the uptake of both tau-PET tracers in the MTL. On the other hand, hypertension showed negative association only with MK uptake. Using Mini-Mental State Examination (MMSE) scores as outcome, we observed that amyloid-β negative individuals with high BMI showed worse cognitive performance as a function of both MK and FTP in the MTL, whereas individuals with vision impairment and hearing loss showed worse cognitive performance as a function of MK only. Amyloid-β positive individuals with hypercholesterolemia and hypertension presented worse cognitive performance as a function of both MK and FTP in the MTL.
CONCLUSION:
In this preliminary analysis, sleep disorders, hypertension, and high BMI were independently associated with tau-PET tracer uptake, with the effects varying according to amyloid-β pathology. These prevalent factors in the elderly also changed the association between tau-PET and cognition, underscoring the need for further studies to better understand their role in modulating this relationship.