Combining Cognitive Markers to Identify Individuals at Increased Dementia Risk: Influence of Modifying Factors and Time to Diagnosis.

Nicola M. Payton,Erika J. Laukka,Miia Kivipelto,Debora Rizzuto,Laura Fratiglioni,Lars Bäckman

doi:10.1017/s1355617720000272

Abstract

We investigated the extent to which combining cognitive markers increases the predictive value for future dementia, when compared to individual markers. Furthermore, we examined whether predictivity of markers differed depending on a range of modifying factors and time to diagnosis. Neuropsychological assessment was performed for 2357 participants (60+ years) without dementia from the population-based Swedish National Study on Aging and Care in Kungsholmen. In the main sample analyses, the outcome was dementia at 6 years. In the time-to-diagnosis analyses, a subsample of 407 participants underwent cognitive testing 12, 6, and 3 years before diagnosis, with dementia diagnosis at the 12-year follow-up. Category fluency was the strongest individual predictor of dementia 6 years before diagnosis [area under the curve (AUC) = .903]. The final model included tests of verbal fluency, episodic memory, and perceptual speed (AUC = .913); these three domains were found to be the most predictive across a range of different subgroups. Twelve years before diagnosis, pattern comparison (perceptual speed) was the strongest individual predictor (AUC = .686). However, models 12 years before diagnosis did not show significantly increased predictivity above that of the covariates. This study shows that combining markers from different cognitive domains leads to increased accuracy in predicting future dementia 6 years later. Markers from the verbal fluency, episodic memory, and perceptual speed domains consistently showed high predictivity across subgroups stratified by age, sex, education, apolipoprotein E ϵ4 status, and dementia type. Predictivity increased closer to diagnosis and showed highest accuracy up to 6 years before a dementia diagnosis. (JINS, 2020, 00, 1-13).

Highlights

Cognitive deficits are a defining feature of preclinical dementia, observable years or even decades before a clinical diagnosis (Boraxbekk et al, 2015; Elias et al, 2000; Rajan, Wilson, Weuve, Barnes, & Evans, 2015)
The present study demonstrates that the addition of tests from multiple cognitive domains increases predictivity of future dementia within 6 years
The cognitive domains that found most useful in predicting dementia were verbal fluency, episodic memory, and perceptual speed

Summary

Introduction

Cognitive deficits are a defining feature of preclinical dementia, observable years or even decades before a clinical diagnosis (Boraxbekk et al, 2015; Elias et al, 2000; Rajan, Wilson, Weuve, Barnes, & Evans, 2015). Tests from the episodic memory (Devanand et al, 2008; Eckerström et al, 2013; Gomar, Bobes-Bascaran, Conejero-Goldberg, Davies, & Goldberg, 2011) or executive function (Eckerström et al, 2015; Ewers et al, 2012) domains are often identified as the best individual predictors of future dementia and Alzheimer's disease (AD). It has been suggested that the best results can be obtained through the combination of multiple tests, spanning several cognitive domains (Belleville et al, 2017; Belleville, Gauthier, Lepage, Kergoat, & Gilbert, 2014; Palmer, Backman, Winblad, & Fratiglioni, 2003; Tian, Bucks, Haworth, & Wilcock, 2003), with combinations among domains of episodic memory and executive function (Albert, Moss, Tanzi, & Jones, 2001; Tierney et al, 1996), or episodic memory and verbal fluency (Gallagher et al, 2010; Palmer et al, 2003), shown to be good at predicting future dementia.

Methods

Results

Conclusion