Modifiable dementia risk factor associations with AT(N) biomarkers: Findings from the European Prevention of Alzheimer’s Dementia study

Abstract

AbstractBackgroundThere is strong evidence that targeting modifiable risk factors can maintain and improve cognitive function, as well as reducing risk for Alzheimer’s disease (AD) and other forms of dementia. Further, a discrete AT(N) profile exists for hallmark biomarkers: amyloid β (A), p‐tau (T) and neurodegeneration (N), to discriminate between AD and non‐AD pathological changes. Despite evidence of a biologically defined AD continuum and modifiable risk amelioration, there is a paucity of studies investigating modifiable risk factors with respect to AT(N) biomarkers. The aim of this study was to investigate how modifiable risk factors relate to the three hallmark AT(N) biomarkers of AD.MethodParticipants were drawn from the European Prevention of Alzheimer’s Disease (EPAD): a prospective, multicentre, pan‐European cohort study. Eligible participants underwent clinical and neurological assessments, brain magnetic resonance imaging, cerebrospinal fluid (CSF) collection, neuropsychological assessment and completed a variety of demographic, clinical, medical history and lifestyle surveys for 10 binary modifiable risk variables. Data were analysed via the NeuroToolKit Application (NTKApp, BetaVersion, 2022). Generalized additive models with penalized regression splines were used to model the associations between modifiable risk factor adherence and AT(N) biological criterion: A (CSF amyloid‐β 42 [Aβ42 pg/mL]); T (CSF phosphorylated‐tau 181 [p‐tau 181 pg/mL]); N (total hippocampal volume [mm3]).ResultOf the 2737 participants included, 56% were female (n = 1526), 39% had at least one APOE ε4 allele (n = 1598), with an average age of 66.0 years and 14.4 years of education. Adjusting for age, sex and APOE carrier status: age, APOE and traumatic brain injury (TBI) were significantly associated with CSF Aβ42; age, APOE, body mass index (BMI) and exercise were significantly associated with CSF p‐tau181; and age, sex and education were significantly associated with total hippocampal volume.ConclusionModifiable risk factors of less education, less exercise, TBI and higher BMI were all significantly associated with increased AD biomarker burden. Our results support previous studies identifying associations between modifiable risk factors and AD and suggest that early intervention strategies focused on education and lifestyle factors and improvements in prevention and treatment of TBI may modify risk profiles associated with cognitive decline.