Aging white matter and cognition: differential effects of regional variations in diffusion properties on memory, executive functions, and speed

Abstract

Disruption of cerebral white matter has been proposed as an explanation for age-related cognitive declines. However, the role of specific regions in specific cognitive declines remains unclear. We used diffusion tensor imaging to examine the associations between regional microstructural integrity of the white matter and performance on age-sensitive cognitive tasks in a sample of healthy adults (N=52, age 19-81 years). White matter integrity was assessed by fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple regions of interest (genu and splenium of corpus callosum, internal capsule limbs, prefrontal, temporal, superior/posterior parietal, occipital white matter) and related to processing speed, working memory, inhibition, task switching, and episodic memory. We found that age and regional white matter integrity differentially influenced cognitive performance. Age-related degradation in anterior brain areas was associated with decreased processing speed and poorer working memory, whereas reduced inhibition and greater task switching costs were linked to decline in posterior areas. Poorer episodic memory was associated with age-related differences in central white matter regions. The observed multiple dissociations among specific age-sensitive cognitive skills and their putative neuroanatomical substrates support the view that age-related cognitive declines are unlikely to stem from a single cause.

Figure 1. Illustration of ROIs used for DTI analyses

White matter regions of interest ROIs manually drawn for obtaining FA and ADC values. (a) genu and splenium of corpus callosum, (b) bilateral anterior, genu, and posterior limbs of internal capsule, (c) bilateral superior prefrontal, (d) bilateral optic radiations, (e) bilateral temporal stem, (f) bilateral superior posterior parietal. Illustrations are displayed on the FA image.

Figure 2. Summary of structure-function dissociation findings: Regional white matter involvement and cognitive performance

Figure 2 illustrates the regional pattern of white matter involvement in the various cognitive domains. ■ = FA; ● = ADC; □ and ○ = non-significant trend for FA and ADC, respectively (p < .06–.09). Speed of processing is related to the DTI-derived measures of primarily anterior (and fronto-parietal) regions; working memory is related to the measures in wide-spread, although largely anterior white matter; episodic memory is primarily associated with the measures of temporal and internal capsule white matter; inhibition is associated with posterior white matter measures and task switching depends on integrity of anterior and posterior regions. PFC = superior frontal gyrus; CCg = corpus callosum genu; ICa = internal capsule anterior limb; ICg = internal capsule genu; ICp = internal capsule posterior limb; Tmp = temporal stem; Par = superior posterior parietal; Occ = occipital white matter; v = verbal; nv = nonverbal; Inh: Stroop = inhibition: Stroop interference; Inh: WCST = inhibition: Wisconsin Card Sort Test perseveration; Switch:1 = single switching cost; Switch: 2 = dual switching cost; CVLT = list free recall; LM = story free recall; MfN = name-picture association recognition.