White matter microstructural correlates of associative learning in the oldest-old

Abstract

Younger-old adults (ages 65-85 years) exhibit declines in the ability to learn associations between events, which has been attributed to structural degradation of white matter tracts connecting the prefrontal cortex to the hippocampus (e.g., fornix) and striatum (e.g., internal capsule). However, deficits in associative learning abilities may increase in oldest-old adults (ages 90+ years) because advanced age is accompanied by (1) accelerated structural degradation of these white matter tracts and (2) increased prevalence of cognitive impairment. Here, we acquired multicompartment diffusion-weighted magnetic resonance imaging data from 22 oldestold adults with normal cognition (n = 15; 92.73 ± 1.67 years) or a diagnosis of cognitive impairment no dementia (CIND; n = 7; 93.29 ± 0.76 years) who also completed an associative learning task. Behavioral results revealed significantly better performance during later task stages, as expected if participants incidentally learned the cue-cue-target associations for frequently occurring event triplets. Moreover, better learning performance was significantly predicted by better microstructure of fronto-striatal white matter (internal capsule). There was no significant effect of cognitive status on learning performance or its relation to white matter microstructure. Thus, associative learning abilities are preserved into the 10 th decade of life and can be attributed to individual differences in the microstructure of white matter tracts connecting the prefrontal cortex to the striatum.