Multidomain Lifestyle Profiles, Biomarker-Defined Alzheimer’s Pathology, and Clinical Expression: Design of the HUNT-ADAPT Study
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Background
It remains unclear why biomarker-defined Alzheimer’s disease neuropathological change (ADNC) leads to cognitive decline and dementia in some individuals but not others. Multidomain lifestyle profiles may influence both pathology risk and clinical expression.
Objectives
To determine whether multidomain lifestyle profiles are associated with (1) the risk of biomarker-defined ADNC and (2) the clinical expression of AD pathology, including longitudinal cognitive test score change and incident dementia.
Design/Setting
Retrospective longitudinal population-based cohort study within the Trøndelag Health Study (HUNT), Norway, including five waves over a 40-year follow-up period.
Participants
The late-life source population comprises 9,956 HUNT4 70+ participants, of whom 5,729 participated in the Ageing in Trøndelag (AiT) follow-up.
Outcome measurements
ADNC is operationalized primarily using plasma phosphorylated tau at threonine 217 (p-tau217), with plasma neurofilament light (NfL) available as a complementary marker of neurodegeneration. In HUNT4 70+, participants aged 70 and older had a standardized cognitive diagnostic assessment, which was repeated at AiT four years later.
Lifestyle Measurements
Multidomain lifestyle will be defined across five domains: nutrition, physical activity and skeletal muscle health, mental and social health, cardiovascular/metabolic status, and cognitive stimulation. Genetic susceptibility, including APOE and genome-wide/polygenic risk measures, and available multi-omics data will be examined as modifiers.
Results
Analyses will examine the associations of multidomain lifestyle profiles and domain-specific exposures with both ADNC risk and clinical expression.
Conclusions
This study will test whether multidomain lifestyle profiles are associated with both the risk of biomarker-defined ADNC and the clinical expression, informing risk stratification and modifiable prevention in AD.
