Associations among executive function Abilities, free Water, and white matter microstructure in early old age

Gustavson, Daniel E.; Archer, Derek B.; Elman, Jeremy A.; Puckett, Olivia K.; Fennema‐Notestine, Christine; Panizzon, Matthew S.; Shashikumar, Niranjana; Hohman, Timothy J.; Jefferson, Angela L.; Eyler, Lisa T.; McEvoy, Linda K.; Lyons, Michael J.; Franz, Carol E.; Kremen, William S.

doi:10.1016/j.nicl.2022.103279

Cited by 5 publications

(4 citation statements)

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“…However, a similar relationship was not found with memory. In general, it appears that WM damage tends to be more disruptive of speeded tasks used in both processing speed and executive function domains compared to non-speeded tasks used to assess other cognitive domains such as episodic memory ( Borghesani et al, 2013 ; Gustavson et al, 2023 ; Vernooij et al, 2009 ). Consistent with these results, a recent study found that FW contributed to fluid (i.e., executive function, working memory, processing speed) but not crystallized (i.e., verbal abilities) measures of cognition ( Gullett et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the moderate strength of relationships observed between BBB kw and cognition, and some ambiguity about the direction of those relationships, another MRI measure of water diffusion, namely diffusion MRI-based free water (FW), has been more strongly correlated with cognition ( Gustavson et al, 2023 ; Maillard et al, 2019 ; Maillard, Hillmer, et al, 2022 ). FW has more consistently shown a negative direction of association with cognitive function ( Gullett et al, 2020 ; Maillard et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…FW has more consistently shown a negative direction of association with cognitive function ( Gullett et al, 2020 ; Maillard et al, 2019 ). Specifically, high FW has been linked to poorer performance on tasks that test speeded response, executive function, or reasoning abilities ( Berger et al, 2022 ; Gullett et al, 2020 ; Gustavson et al, 2023 ) as well as poorer performance on memory and global cognitive function tasks ( Maillard et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults

Pappas,

Bauer,

Zachariou

et al. 2024

Imaging Neuroscience

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Vascular risk factors contribute to cognitive aging, with one such risk factor being dysfunction of the blood brain barrier (BBB). Studies using non-invasive magnetic resonance imaging (MRI) techniques, such as diffusion prepared arterial spin labeling (DP-ASL), can estimate BBB function by measuring water exchange rate (kw). DP-ASL kw has been associated with cognition, but the directionality and strength of the relationship is still under investigation. An additional variable that measures water in extracellular space and impacts cognition, MRI free water (FW), may help explain prior findings. A total of 94 older adults without dementia (Mean age = 74.17 years, 59.6% female) underwent MRI (DP-ASL, diffusion weighted imaging (DWI)) and cognitive assessment. Mean kw was computed across the whole brain (WB), and mean white matter FW was computed across all white matter. The relationship between kw and three cognitive domains (executive function, processing speed, memory) was tested using multiple linear regression. FW was tested as a mediator of the kw-cognitive relationship using the PROCESS macro. A positive association was found between WB kw and executive function [F(4,85) = 7.81, p < .001, R2= 0.269; β = .245, p = .014]. Further, this effect was qualified by subsequent results showing that FW was a mediator of the WB kw-executive function relationship (indirect effect results: standardized effect = .060, bootstrap confidence interval = .0006 to .1411). Results suggest that lower water exchange rate (kw) may contribute to greater total white matter (WM) FW which, in turn, may disrupt executive function. Taken together, proper fluid clearance at the BBB contributes to higher-order cognitive abilities.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults

Pappas,

Bauer,

Zachariou

et al. 2024

Imaging Neuroscience

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“…Its impairment is a small but noticeable cognitive deficit in MCI besides impaired memory. Most of the existing imaging studies on executive impairment focused on the prefrontal/cerebellar cortex or white matter ( Friedman and Robbins, 2022 ; Li et al, 2022b ; Gustavson et al, 2023 ), and there are a few studies on the correlation between neuro metabolites and executive function in the ACC and PCC. The relationship between the execution and GABA, which has been discussed previously, was controversial ( Marenco et al, 2018 ; Oeltzschner et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment

Qin

Liu

et al. 2023

Front. Neurosci.

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Background and purposeExecutive function impairment, a slight but noticeable cognitive deficit in mild cognitive impairment (MCI) patients, is influenced by gamma-aminobutyric acid (GABA) levels. Reduced cognitive function is accompanied by thinning of the cerebral cortex, which has higher GABA levels than white matter. However, the relationships among GABA levels, cortical thickness, and executive function in MCI patients have not yet been elucidated. We investigated the relationships among GABA levels, cortical thickness, and executive function in MCI patients.MethodsIn this study, a total of 36 MCI patients and 36 sex-, age-, and education-matched healthy controls (HC) were recruited. But 33 MCI patients and 35 HC were included because of head motion or poor data quality for three MCI patients and one HC. The levels of gamma-aminobutyric acid plus relative to creatine (GABA+/Cr) and glutamate-glutamine relative to creatine (Glx/Cr) in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were measured using the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. Metabolite ratios, cortical thickness, and executive function and their interrelationships were determined in the MCI and HC groups.ResultsPatients with MCI showed lower GABA+/Cr levels in the ACC and PCC. Combined levels of GABA+ and Glx in the ACC and GABA+ in the PCC showed good diagnostic efficacy for MCI (AUC: 0.82). But no differences in cortical thickness were found between the two groups. In the MCI group, lower GABA+/Cr level was correlated to worse performance on the digit span test backward, and the shape trail test-B. The cortical thickness was not associated with GABA+ levels and executive function in patients.ConclusionThese results implied that decreased GABA levels in the ACC and PCC had a critical role in the early diagnosis of impaired executive function of MCI. Therefore, GABA in the ACC and PCC could be a potential diagnostic marker of the executive function decline of MCI.

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The Effects of Simultaneous Aerobic Exercise and Video Game Training on Executive Functions and Brain Connectivity in Older Adults

Gui,

Cui,

Miao

et al. 2024

The American Journal of Geriatric Psychiatry

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Associations among executive function Abilities, free Water, and white matter microstructure in early old age

Cited by 5 publications

References 82 publications

MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults

MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults

Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment

The Effects of Simultaneous Aerobic Exercise and Video Game Training on Executive Functions and Brain Connectivity in Older Adults

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