Multidomain Lifestyle Profiles, Biomarker-Defined Alzheimers Pathology, and Clinical Expression: Design of the HUNT-ADAPT Study
OHara-Veintimilla, K.; Lind Melbye, E.; Borda, M. G.; Mallinson, P. A.; Sunde, A. L.; Leuzy, A.; van der Giezen, M.; Masci, P.-G.; Seyoum, Y.; Pozuelo Moyano, B.; Botero-Rodriguez, F.; Craig, M. C.; Guo, L.; Xue, L.; Skjellegrind, H. K.; Oesterhus, R.; Vik-Mo, A. O.; Tovar-Rios, D. A.; Zuidgeest, M. G.; Frohlich, H.; de Lucia, C.; Siow, R.; Kivipelto, M.; Andreassen, O. A.; Selbaek, G.; Aarsland, D.
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Background: It remains unclear why biomarker-defined Alzheimers 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 Trondelag 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 Trondelag (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.
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