Data-driven health deficit assessment improves a frailty index’s prediction of current cognitive status and future conversion to dementia: results from ADNI

Frailty is a dementia risk factor commonly measured by a frailty index (FI). The standard procedure for creating an FI requires manually selecting health deficit items and lacks criteria for selection optimization. We hypothesized that refining the item selection using data-driven assessment improves sensitivity to cognitive status and future dementia conversion, and compared the predictive value of three FIs: a standard 93-item FI was created after selecting health deficit items according to standard criteria (FI(s)) from the ADNI database. A refined FI (FI(r)) was calculated by using a subset of items, identified using factor analysis of mixed data (FAMD)-based cluster analysis. We developed both FIs for the ADNI1 cohort (n = 819). We also calculated another standard FI (FI(c)) developed by Canevelli and coworkers. Results were validated in an external sample by pooling ADNI2 and ADNI-GO cohorts (n = 815). Cluster analysis yielded two clusters of subjects, which significantly (p(FDR) < .05) differed on 26 health items, which were used to compute FI(r). The data-driven subset of items included in FI(r) covered a range of systems and included well-known frailty components, e.g., gait alterations and low energy. In prediction analyses, FI(r) outperformed FI(s) and FI(c) in terms of baseline cognition and future dementia conversion in the training and validation cohorts. In conclusion, the data show that data-driven health deficit assessment improves an FI's prediction of current cognitive status and future dementia, and suggest that the standard FI procedure needs to be refined when used for dementia risk assessment purposes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00669-2.