Abstract
BackgroundThe 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.MethodsOne thousand ten 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.ResultsAge, 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.ConclusionsATN-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.
Highlights
The Amyloid/Tau/Neurodegeneration (ATN) framework has been proposed as a means of evidencing the biological state of Alzheimer’s disease (AD)
Despite continuous measures of vascular risk factors relating to ATN biomarkers, little is known about how composite risk scores for dementia relate to ATN-defined biomarker groups among cognitively healthy individuals
The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score was originally validated by its prediction of incident dementia 20 years later [25]; the Framingham general cardiovascular score showed an association with 10-year cognitive decline [21]; and the Framingham stroke score showed significant association with contemporaneous cognitive function [9]
Summary
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 provides an important opportunity for targeted recruitment into AD interventional studies. Predicting ATN status through known risk factors and derived scores may provide an important opportunity for aiding preclinical diagnosis and targeted recruitment into AD interventional studies. Despite continuous measures of vascular risk factors relating to ATN biomarkers, little is known about how composite risk scores for dementia relate to ATN-defined biomarker groups among cognitively healthy individuals. Such validation would support the utility of a single vascular risk score for screening high-risk individuals into disease-modifying intervention studies. A recent study in middle-aged individuals compared them in relation to cognitive decline over 10 years [20] finding that all three predicted 10-year cognitive decline, with Framingham risk scores showing greater strength of association relative to CAIDE
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