Association of years to parent’s sporadic onset and risk factors with neural integrity and Alzheimer’s biomarkers

Objective: To evaluate the hypothesis that proximity to parental age at onset (AAO) in sporadic Alzheimer’s disease (AD) is associated with greater AD and neural injury biomarker alterations during midlife and to assess the role of non-modifiable and modifiable factors. Methods: This observational study included 290 cognitively unimpaired (CU) participants with family history (FH) of clinically-diagnosed sporadic AD (aged 49-73) from the ALFA study. [18F]Flutemetamol-PET SUVRs, CSF Aβ42/40 ratio and p-tau were used as AD biomarkers. Hippocampal volumes and CSF t-tau were used as neural injury biomarkers. Mental and vascular health proxies were calculated. In multiple regression models, we assessed the effect of proximity to parental AAO and its interaction with age on AD and neural injury biomarkers. Then, we evaluated the effects of FH load (number of parents affected), sex, APOE-Ɛ4, education, vascular and mental health. Results: Proximity to parental AAO was associated with β-a...