Microstructural white matter changes mediate age‐related cognitive decline on the Montreal Cognitive Assessment (MoCA)

Abstract

Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.

Dynamics of cognitive control: Theoretical bases, paradigms, and a view for the future

“…For instance, reduced efficiency of top‐down control mechanisms (e.g., CRUNCH, Reuter‐Lorenz & Cappell, ) can incorporate both reduced structural/functional connectivity and increased frontal and bilateral cortical recruitment at lower levels of cognitive load in older adults (see Schneider‐Garces et al, ). Importantly, declines in prefrontal cortex tissue and cognitive control performance in older adults are increasingly shown to vary with the presence of modifiable cardiovascular and cerebrovascular factors (e.g., Chiarelli et al, ; Fabiani, Gordon et al, ; Fabiani, Low et al, ; Jolly et al, ; Tan et al, ; Zimmerman et al, ) and to be, at least partly, mitigated by cardiorespiratory fitness (Fletcher et al, ; Gordon et al, ; Kramer et al, ). Exercise intervention programs appear to stave off, if not reverse, some of the declines in cognitive control found in older adults (Bherer, Erickson, & Liu‐Ambrose, ; Colcombe & Kramer, ; Gajewski & Falkenstein, ; Heyn, Abreu, & Ottenbacher, ; Smith et al, ) and more recently in inactive children (Chaddock et al, ; Hillman, Erickson, & Kramer, ).…”

Age‐related decline in task switching is linked to both global and tract‐specific changes in white matter microstructure

“…The few studies do report RaD have found it to be more sensitive than other DTI measures to cognitive performance in older adults [Borghesani et al, ; Haász et al, ]. Jolly et al [] showed that, compared with cortical atrophy, white matter hyperintensities and other DTI measures, RaD was the strongest predictor of scores on the Montreal Cognitive Assessment [MoCA; Nasreddine et al, ]. Moreover, whole brain RaD was a better predictor of MoCA scores than RaD in any one of the 18 white matter tracts extracted based on the probabilistic white matter tract atlas from the John Hopkins University [Hua et al, ].…”

“…Moreover, whole brain RaD was a better predictor of MoCA scores than RaD in any one of the 18 white matter tracts extracted based on the probabilistic white matter tract atlas from the John Hopkins University [Hua et al, ]. In fact, the relationship between MoCA scores and RaD in each individual white matter tract did not remain significant when controlling for whole brain RaD [Jolly et al, ]. This is not surprising as the MoCA is a global cognitive screening tool that assesses memory, attention and executive functions.…”

“…In contrast, we expect that, consistent with a mediating role of white matter microstructure on task switching performance, the relationship between mixing cost and RaD in frontoparietal tracts will remain significant after controlling for age. Finally, we have previously shown that the relationship between brain white matter health and both global cognitive performance [Jolly et al, ] and brain arterial pulsatility [Jolly et al, ] is greater in the presence of cardiovascular risk factors. Therefore, we predict that the association between task switching performance and white matter RaD will be greater in adults with cardiovascular risk factors.…”

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

“…There is also evidence that vascular risk factors may influence brain anatomy and cognitive function even in the absence of stroke or Alzheimer’s disease. For instance, Raz and colleagues (2007) showed an association between vascular risk factors, smaller prefrontal volumes, and lower scores on tests of fluid intelligence (see also Jolly et al, 2016; 2017). Similarly, a meta-analysis examining the effects of peripheral blood pressure reported that 26 of the 28 studies included showed an association between hypertension and volumetric reductions in the brain, with particularly strong effects in the frontal and temporal lobes (Beauchet et al, 2013).…”