| Summary: | <p><strong>Background:</strong> The Amyloid/Tau/Neurodegeneration (ATN) framework has been proposed as a means
of evidencing the biological state of Alzheimer’s disease (AD). Predicting ATN status in pre-dementia
individuals therefore provides an important opportunity for targeted recruitment into AD
interventional studies. We investigated the extent to which ATN-defined biomarker status can be
predicted by known AD risk factors as well as vascular-related composite risk scores.</p>
<p><strong>Methods:</strong> 1010 cognitively healthy older adults were allocated to one of five ATN-defined biomarker
categories. Multinomial logistic regression tested risk factors including age, sex, education, APOE4,
family history of dementia, cognitive function, vascular risk indices (high systolic blood pressure,
body mass index (BMI), high cholesterol, physical inactivity, ever smoked, blood pressure
medication, diabetes, prior cardiovascular disease, atrial fibrillation and white matter lesion (WML)
volume), and three vascular-related composite scores, to predict five ATN subgroups; ROC curve
models estimated their added value in predicting pathology.</p>
<p><strong>Results:</strong> Age, APOE4, family history, BMI, MMSE, and white matter lesions (WML) volume differed
between ATN biomarker groups. Prediction of Alzheimer’s disease pathology (versus normal AD
biomarkers) improved by 7% after adding family history, BMI, MMSE and WML to a ROC curve that
included age, sex and APOE4. Risk composite scores did not add value.</p>
<p><strong>Conclusions:</strong> ATN-defined Alzheimer’s disease biomarker status prediction among cognitively
healthy individuals is possible through a combination of constitutional and cardiovascular risk factors
but established dementia composite risk scores do not appear to add value in this context.</p>
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