Fronto-striatal dopamine D2 receptor availability is associated with cognitive variability in older individuals with low dopamine integrity

Saana M Korkki,Katrine Riklund,Lars Bäckman,Nina Karalija,Ulman Lindenberger,Douglas D Garrett,Martin Lövdén,Goran Papenberg,Lars Nyberg

doi:10.1038/s41598-021-00106-y

Abstract

Within-person, moment-to-moment, variability in behavior increases with advancing adult age, potentially reflecting the influence of reduced structural and neurochemical brain integrity, especially that of the dopaminergic system. We examined the role of dopamine D2 receptor (D2DR) availability, grey-, and white-matter integrity, for between-person differences in cognitive variability in a large sample of healthy older adults (n = 181; 64–68 years) from the Cognition, Brain, and Aging (COBRA) study. Intra-individual variability (IIV) in cognition was measured as across-trial variability in participants’ response times for tasks assessing perceptual speed and working memory, as well as for a control task of motor speed. Across the whole sample, no associations of D2DR availability, or grey- and white-matter integrity, to IIV were observed. However, within-person variability in cognition was increased in two subgroups of individuals displaying low mean-level cognitive performance, one of which was characterized by low subcortical and cortical D2DR availability. In this latter group, fronto-striatal D2DR availability correlated negatively with within-person variability in cognition. This finding suggests that the influence of D2DR availability on cognitive variability may be more easily disclosed among individuals with low dopamine-system integrity, highlighting the benefits of large-scale studies for delineating heterogeneity in brain-behavior associations in older age.

Highlights

Within-person, moment-to-moment, variability in behavior increases with advancing adult age, potentially reflecting the influence of reduced structural and neurochemical brain integrity, especially that of the dopaminergic system
From the broad cognitive test battery of the COBRA study[61], the present analyses focused on tasks that allowed for the assessment of individual variability (IIV) through collection of trials-specific reaction time (RT)
IIV in RT correlated positively with mean RT in both perceptual speed, r = 0.86, confidence intervals (CIs) [0.82, 0.89], p < 0.001, and 1-back, r = 0.29, CI [0.14, 0.43], p < 0.001, indicating that more variable individuals were generally slower to respond across the tasks

Summary

Introduction

Within-person, moment-to-moment, variability in behavior increases with advancing adult age, potentially reflecting the influence of reduced structural and neurochemical brain integrity, especially that of the dopaminergic system. Between-person differences in mean RT and intra-individual variability (IIV) in RT have been found to predict unique variance in cognitive performance cross-sectionally[3,12], with longitudinal evidence further suggesting utility of IIV in predicting cognitive decline in healthy a ging[13,14,15], as well as mild cognitive impairment and d ementia[16,17], beyond measures of mean performance[13,16] These observations have led to proposals that IIV may serve as a sensitive index of neural integrity, supported by neuroimaging studies linking multiple indices of brain integrity to within-person variability in b ehavior[2,18]. MacDonald et al.[55] found age-related reductions in D1 receptor availability in the cingulo-fronto-parietal network to mediate agerelated increases in IIV observed during an attentional interference task

Methods

Results

Conclusion