Proximity to parental age at onset exacerbates amyloid burden while mental conditions exacerbate neural loss during midlife Neuroimaging / Optimal neuroimaging measures for early detection

• Published in: Alzheimer's & dementia Vol. 16; no. S5
• Main Authors: Arenaza‐Urquijo, Eider M, Salvadó, Gemma, Operto, Greg, Minguillón, Carolina, Sánchez‐Benavides, Gonzalo, Crous‐Bou, Marta, Grau‐Rivera, Oriol, Sala‐Vila, Aleix, Falcon, Carles, Suárez‐Calvet, Marc, Zetterberg, Henrik, Blennow, Kaj, Gispert, Juan Domingo, Molinuevo, Jose Luis
• Format: Journal Article
• Language: English
• Published: 01.12.2020
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.045171

Abstract Background The identification of the earliest biomarker changes and modifiable factors to be targeted in early interventions is crucial for Alzheimer’s disease (AD) prevention. The objective were (1) to evaluate the hypothesis that proximity to parental age at onset (AAO) in sporadic AD is associated with greater AD and neural injury biomarker alterations during midlife and (2) to assess the role of non‐modifiable and modifiable factors on AD and neural injury biomarkers. Method A total of 291 cognitively unimpaired (CU) participants with family history (FH) of sporadic AD (aged 49‐73) from the ALFA study. [18F]Flutemetamol‐PET SUVRs, CSF Aβ42/40 and p‐tau were used as AD biomarkers. Hippocampal volumes and CSF t‐tau were used as neural injury biomarkers (Elecsys® immunoassays, Roche diagnostic). Mental and vascular health proxies were calculated. We ran multiple regression models to assess the effect of proximity to parental AAO and its interaction with age on AD and neural injury biomarkers. We also evaluated the effects of FH load (number of parents affected), sex, APOE‐Ɛ4 , education, vascular and mental health. Result 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 (see Fig1). 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 (see Fig1). Conclusion 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.