Cognitive Profiling Related to Cerebral Amyloid Beta Burden Using Machine Learning Approaches

Background: Cerebral amyloid beta (A beta) is a hallmark of Alzheimer's disease (AD). A beta can be detected in vivo with amyloid imaging or cerebrospinal fluid assessments. However, these technologies can be both expensive and invasive, and their accessibility is limited in many clinical settings. Hence the current study aims to identify multivariate cost-efficient markers for A beta positivity among non-demented individuals using machine learning (ML) approaches. Methods: The relationship between cost-efficient candidate markers and A beta status was examined by analyzing 762 participants from the Alzheimer's Disease Neuroimaging Initiative-2 cohort at baseline visit (286 cognitively normal, 332 with mild cognitive impairment, and 144 with AD; mean age 73.2 years, range 55-90). Demographic variables (age, gender, education, and APOE status) and neuropsychological test scores were used as predictors in an ML algorithm. Cerebral A beta burden and A beta positivity were measured using F-18-florbetapir positron emission tomography images. The adaptive least absolute shrinkage and selection operator (LASSO) ML algorithm was implemented to identify cognitive performance and demographic variables and distinguish individuals from the population at high risk for cerebral A beta burden. For generalizability, results were further checked by randomly dividing the data into training sets and test sets and checking predictive performances by 10-fold cross-validation. Results: Out of neuropsychological predictors, visuospatial ability and episodic memory test results were consistently significant predictors for A beta positivity across subgroups with demographic variables and other cognitive measures considered. The adaptive LASSO model using out-of-sample classification could distinguish abnormal levels of A beta. The area under the curve of the receiver operating characteristic curve was 0.754 in the mild change group, 0.803 in the moderate change group, and 0.864 in the severe change group, respectively. Conclusion: Our results showed that the cost-efficient neuropsychological model with demographics could predict A beta positivity, suggesting a potential surrogate method for detecting A beta deposition non-invasively with clinical utility. More specifically, it could be a very brief screening tool in various settings to recruit participants with potential biomarker evidence of AD brain pathology. These identified individuals would be valuable participants in secondary prevention trials aimed at detecting an anti-amyloid drug effect in the non-demented population.