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. 2020 Nov 9;12(1):143.
doi: 10.1186/s13195-020-00711-5.

Prediction of Alzheimer's disease biomarker status defined by the 'ATN framework' among cognitively healthy individuals: results from the EPAD longitudinal cohort study

Catherine M Calvin  1 , Casper de Boer  2 , Vanessa Raymont  1 , John Gallacher  1 , Ivan Koychev  3 ; European Prevention of Alzheimer’s Dementia (EPAD) Consortium
Affiliations

Prediction of Alzheimer's disease biomarker status defined by the 'ATN framework' among cognitively healthy individuals: results from the EPAD longitudinal cohort study

Catherine M Calvin et al. Alzheimers Res Ther. .

Abstract

Background: 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.

Methods: One 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.

Results: 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.

Conclusions: 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.

Keywords: ATN framework; Risk scores; White matter lesions volume.

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Conflict of interest statement

JG was the recipient of an MRC grant for staff, which included a salary for CMC and IK. The authors declare no other conflicts of interest.

Figures

Fig. 1
Fig. 1
Age- and sex-adjusted odds ratios and 95% confidence intervals for the associations of constitutional- and cognitive-risk factors and amyloid-beta pathology (A+), p-Tau pathology (T+) and neurodegeneration (N+), respectively. Statistically significant P values are indicated (p < 0.05)
Fig. 2
Fig. 2
Age- and sex-adjusted odds ratios and 95% confidence intervals for the associations of vascular risk factors and amyloid-beta pathology (A+), p-Tau pathology (t+) and neurodegeneration (N+), respectively. Statistically significant P values are indicated (p < 0.05)
Fig. 3
Fig. 3
ROC curve showing improvement to the discriminative accuracy of predicting Alzheimer’s disease vs normal AD biomarkers by cumulative risk factors
See this image and copyright information in PMC

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