Cognitive variability—A marker for incident MCI and AD: An analysis for the Alzheimer's Disease Neuroimaging Initiative

Abstract

IntroductionThe potential of intra-individual cognitive variability (IICV) to predict incident mild cognitive impairment (MCI) or Alzheimer's disease (AD) was examined and compared to well-established neuroimaging and genetic predictors.MethodsIICV was estimated using four neuropsychological measures for n = 1324 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were cognitively healthy or diagnosed with MCI at baseline. IICV was used to predict time to incident MCI or AD, and compared to hippocampal volume loss and APOE ε4 status via survival analysis.ResultsIn survival analyses, controlling for age, education, baseline diagonosis, and APOE ε4 status, likelihood ratio tests indicate that IICV is associated with time to cognitive status change in the full sample (P < .0001), and when the sample was restricted to individuals with MCI at baseline (P < .0001).DiscussionThese findings suggest IICV may be a low-cost, noninvasive alternative to traditional AD biomarkers.

Characterizing the Effects of Sex, APOE ɛ4, and Literacy on Mid-life Cognitive Trajectories: Application of Information-Theoretic Model Averaging and Multi-model Inference Techniques to the Wisconsin Registry for Alzheimer’s Prevention Study

“…In contrast, predicted IICV increased with age at higher literacy levels (and for both sexes), suggesting probable worsening in memory and/or executive function relative to premorbid verbal abilities. This pattern corresponds to other studies that have shown that higher IICV (calculated using variables similar to those we used) predicts MCI, AD or AD pathology ((E. D. Anderson et al, 2016; Gleason, Norton, Anderson, Wahoske, Washington, Umucu, Koscik, Dowling, Johnson, Carlsson, et al., 2017; Holtzer et al, 2008; Koscik et al, 2016)). The former pattern suggests that future studies could examine whether the risk-indicating value of IICV varies across underlying characteristics such as sex and literacy.…”

“…Given recent results in WRAP and other studies suggesting that higher intraindividual cognitive variability (IICV) across tests at a given visit predicts increased risk of subsequent decline or AD pathology (Anderson et al, 2016; Gleason, Norton, Anderson, Wahoske, Washington, Umucu, Koscik, Dowling, Johnson, & Carlsson, 2017; Holtzer, Verghese, Wang, Hall, & Lipton, 2008; Koscik et al, 2016), we also characterized how IICV varied by sex, literacy, APOE, and age in our sample. Specifically, we calculated “4-Test IICV” as the standard deviation of z-scores of AVLT Total and Delay, Trails B, and the Wide Range Achievement Test (3 rd ed., “WRAT”) reading recognition subtest standard score (Wilkinson, 1993); AVLT Delay, Trails B, and WRAT were Box-Cox transformed prior to z-scoring (AVLT Delay had a constant of 1 added to all scores before transformation) The WRAT Reading score when used in middle-aged and older adults is accepted as a stable proxy for premorbid verbal abilities and quality of education (Ashendorf, Jefferson, Green, & Stern, 2009; Manly et al, 2003; Olsen, Fellows, Rivera-Mindt, Morgello, & Byrd, 2015).…”

Identification of a simple and novel cut-point based CSF and MRI signature for predicting Alzheimer’s disease progression that reinforces the 2018 NIA-AA research framework

“…Multiple potential biomarkers have been identified to aid in the prediction of conversion of MCI to AD. For example, cognitive and behavioral biomarkers have been proposed to identify individuals at high-risk for conversion [11-13]. In addition, biomarkers based on brain imaging or measurements in bodily fluids have been identified (for recent reviews see [14, 15]).…”

Characterizing the effects of sex, APOE ɛ4, and literacy on mid-life cognitive trajectories: Application of Information-Theoretic model-averaging and multi-model inference techniques to the Wisconsin Registry for Alzheimer’s Prevention Study

“…In our data, lower literacy was associated with steady age-related decline in 4-Test IICV with higher IICV consistently observed among women; at higher literacy levels, IICV was generally higher among men and increased with age for both sexes. Our 4-Test IICV is the same as used in previous WRAP analysis and similar to what has been used in other analyses (Holtzer et al, 2008;Anderson et al, 2016, Gleason et al, 2017 which indicate higher IICV predicts MCI and AD. As IICV is developed further as a potential cognitive marker for risk of later decline in the AD continuum, future studies should examine whether riskindicating value is constant across underlying demographics such as age, sex, and literacy.…”

“…Given recent results in WRAP and other studies suggesting that higher intraindividual cognitive variability (IICV) at a given visit predicts increased risk of subsequent decline (E. D. Anderson et al, 2016;Gleason et al, 2017;Holtzer, Verghese, Wang, Hall, & Lipton, 2008;Koscik et al, 2016), we also characterized how IICV varied by sex, literacy, APOE, and age in our sample. We calculated two versions of IICV.…”