Data from: 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-amyloid, but not
with neural injury biomarkers, and interacted with sex and age, showing
women and older participants increased β-amyloid. FH load and APOE-Ɛ4
showed independent contributions to β-amyloid load. Education, vascular
and mental health proxies were not associated with AD biomarkers. However,
lower mental health proxies were associated with decreased hippocampal
volumes with age. Conclusions: The identification of the earliest
biomarker changes and modifiable factors to be targeted in early
interventions is crucial for AD prevention. Proximity to parental AAO may
offer a timeline for detection of incipient β-amyloid changes in women. In
risk-enriched middle-aged cohorts, mental health may be a target for early
interventions. Classification of evidence: This study provides Class II
evidence that in CU adults with FH of sporadic AD proximity to parental
AAO was associated with β-amyloid but not with neural injury biomarkers.