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

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=16

YEAR=2024

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1346214

DOI=10.3389/fnagi.2024.1346214

ISSN=1663-4365

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>A total of 1,434 participants were included (56% women, 39% <italic>APOE</italic> ε4+) with an average age of 65.5 (± 7.2) years. We found that modifiable risk factors of less education (<italic>t</italic> = 3.9, <italic>p</italic> &lt; 0.001), less exercise (<italic>t</italic> = 2.1, <italic>p</italic> = 0.034), traumatic brain injury (<italic>t</italic> = −2.1, <italic>p</italic> = 0.036), and higher body mass index (<italic>t</italic> = −4.5, <italic>p</italic> &lt; 0.001) were all significantly associated with higher AD biomarker burden.</p></sec><sec><title>Discussion</title><p>This cross-sectional study provides further support for modifiable risk factors displaying neuroprotective associations with the characteristic AT(N) biomarkers of AD.</p></sec>