Intraindividual Cognitive Variability in Middle Age Predicts Cognitive Impairment 8-10 Years Later: Results from the Wisconsin Registry for Alzheimer's Prevention

Abstract

Objectives: Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample.

Methods: Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer's Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer's disease). The primary outcome was Wave 4 cognitive status ("cognitively normal" vs. "impaired") determined by consensus conference; "impaired" included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: "6 Factor IICV" and "4 Test IICV". Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable.

Results: Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment.

Conclusions: While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016-1025).

Keywords: Alzheimer’s disease; Mild cognitive impairment; Neuropsychological tests; Prodromal period; Psychometrics; Risk screening.

Figure 1

Correlogram of 6 Factor IICV and 4 Test IICV with variables that contribute to each test and with baseline age. Trails A and B were log-transformed. Correlations with p<.05 also have a colored dot overlapping with the correlation coefficient to provide an easy means to visualize the magnitude and direction of correlations: larger dots indicate larger coefficients; blue shades indicate positive correlations while yellow to red shades indicate negative correlations.

Figure 2

Bar graphs of proportion in the cognitively impaired group at Wave 4 within each of the subgroups representing risk based on falling in the “risk tertile” for AVLT or Trails B or having an IICV risk pattern based on the IQR's of AVLT, Trails B, and WRAT-III reading. Denominators for each of the 8 groups below are 251, 127, 17, 112, 12, 88, 0, and 77, respectively.