Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

Background: CSF amyloid and tau biomarkers are now the gold standard for predicting Alzheimer pathology. However, measuring CSF biomarkers is invasive and impractical for large-scale screening. I tested how well simple clinical items and CSF biomarkers can predict post mortem Alzheimer pathology in non-demented people. Methods: 30 simple clinical items were used or CSF biomarkers to predict Alzheimer patho-logy via a machine-learning algorithm (conditional random forest - CRF). I then compared the accuracies of the predictions using areas under receiver operating characteristic curves (ROC-AUCs). Results: 332 people provided clinical and neuro pathological data, of whom 144 were initially non-demented (MMSE 25-30 and no major problems with activities of daily living). 127/332 (49 initially non-demented) also provided CSF. The median interval to death was 5.0 years. 144/332 cases were initially non-demented and 21/144 had NIA-Reagan classifications of high-probability Alzheimer disease. The corresponding numbers for those who provided CSF were 49 and 9. The ROC-AUCs were 88.0% for predictions of Alzheimer pathology based on the clinical items and 87.5% for predictions from the CSF biomarkers. The most important clinical predictors were informants' views on short-term memory and episodic recall. Conclusions: Predictions of post mortem Alzheimer pathology derived from 30 simple clinical items in non-demented people were as accurate as those from CSF biomarkers. So, predictions of Alzheimer pathology from simple clinical items may facilitate screening to select people with pre-clinical Alzheimer's disease for trials of pathology-modifying agents.

Biography

Jonathan Williams qualified as a physician from Cambridge and Birmingham Universities before completing his Ph.D. in Experimental Psychology at Oxford. He then trained in psychiatry and undertook postdoctoral studies that intercalated clinical and academic work at Oxford, including 10 years at The Oxford Project to Investigate Memory and Ageing (OPTIMA). He now works as a consultant in Psychiatry of Older Adults in Hamilton, New Zealand. He has published 40 refereed papers.