Modifiable dementia risk factors and AT(N) biomarkers: findings from the EPAD cohort

Eddy Roccati; Aidan David Bindoff; Jessica Marie Collins; Joshua Eastgate; Jay Borchard; Jane Alty; Anna Elizabeth King; James Clement Vickers; Margherita Carboni; Chad Logan; EPAD Consortium

doi:10.3389/fnagi.2024.1346214

Modifiable dementia risk factors and AT(N) biomarkers: findings from the EPAD cohort

Front Aging Neurosci. 2024 Feb 7:16:1346214. doi: 10.3389/fnagi.2024.1346214. eCollection 2024.

Affiliations

¹ Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia.
² Royal Hobart Hospital, Hobart, TAS, Australia.
³ Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
⁴ Roche Diagnostics GmbH, Penzberg, Germany.

Abstract

Introduction: Modifiable risk factors account for a substantial proportion of Alzheimer's disease (AD) cases and we currently have a discrete AT(N) biomarker profile for AD biomarkers: amyloid (A), p-tau (T), and neurodegeneration (N). Here, we investigated how modifiable risk factors relate to the three hallmark AT(N) biomarkers of AD.

Methods: Participants from the European Prevention of Alzheimer's Dementia (EPAD) study underwent clinical assessments, brain magnetic resonance imaging, and cerebrospinal fluid collection and analysis. Generalized additive models (GAMs) with penalized regression splines were modeled in the AD Workbench on the NTKApp.

Results: A total of 1,434 participants were included (56% women, 39% APOE ε4+) with an average age of 65.5 (± 7.2) years. We found that modifiable risk factors of less education (t = 3.9, p < 0.001), less exercise (t = 2.1, p = 0.034), traumatic brain injury (t = -2.1, p = 0.036), and higher body mass index (t = -4.5, p < 0.001) were all significantly associated with higher AD biomarker burden.

Discussion: This cross-sectional study provides further support for modifiable risk factors displaying neuroprotective associations with the characteristic AT(N) biomarkers of AD.

Keywords: Alzheimer’s disease; amyloid-beta; biomarkers; modifiable dementia risk; neurodegeneration; tau.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. EPAD has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD grant agreement number 115736.