Regional differences in the link between water exchange rate across the blood–brain barrier and cognitive performance in normal aging

Abstract

The blood–brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61–84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults.

Association of pulsatility index with total burden of cerebral small vessel disease and cognitive impairment

“…This was mainly associated with microangiopathy, which results in atherosclerosis, narrowing of vessel diameters, and decreased cerebral blood flow (Malojcic et al., 2017; Sabayan et al., 2012; Vicenzini et al., 2007). Vascular sclerosis and chronic under‐perfusion can lead to disruption of the blood–brain barrier (Yang et al., 2017), ultimately manifesting as cognitive and sensorimotor decline and causing cognitive dysfunction (Marshall et al., 2012; Zachariou et al., 2024). Our study revealed a noteworthy association between PI and CSVD total burden and CI, and the predictive value of PI combined with CSVD total burden for CI was higher than that alone; therefore, PI combined with total burden score was clinically used for better prediction of cognitive functioning in CSVD patients.…”

Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study

“…Studies in other cognitive and neurological disorders have provided evidence that BBB permeability is related to cognitive function [ 19 ]. In Alzheimer’s disease, it has been shown that PS is inversed related to memory and composite cognitive scores and also associated with beta-amyloid and phosphorylated tau concentrations [ 20 ].…”

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

“…Thus, as a potentially sensitive, non-invasive metric of BBB function, it is important to gain a greater understanding of the interplay between BBB kw and cognition in older adults. A relationship between BBB kw and cognitive performance has been reported ( Gold et al, 2021 ; Shao et al, 2019 ; Uchida et al, 2022 ; Zachariou et al, 2023 ). Specifically, BBB kw has been associated with memory and executive function performance ( Gold et al, 2021 ; Uchida et al, 2022 ; Zachariou et al, 2023 ).…”

“…A relationship between BBB kw and cognitive performance has been reported ( Gold et al, 2021 ; Shao et al, 2019 ; Uchida et al, 2022 ; Zachariou et al, 2023 ). Specifically, BBB kw has been associated with memory and executive function performance ( Gold et al, 2021 ; Uchida et al, 2022 ; Zachariou et al, 2023 ). In these studies, higher kw (a greater water exchange rate) and better memory or executive function was observed, although results were region specific and revealed small effects in some cases.…”

“…The study of vascular contributors to cognitive impairment and dementia (VCID) has gained increased attention ( Corriveau et al, 2016 ; Zlokovic et al, 2020 ) as poorer vascular health (e.g., small vessel disease, hypertension) can contribute to cognitive deficits ( Hamilton et al, 2021 ; Ou et al, 2020 ). VCID includes impaired blood brain barrier (BBB) function, which has been tied to cognitive performance as well as cognitive impairment ( Montagne et al, 2015 ; Verheggen et al, 2020 ; Zachariou et al, 2023 ). The BBB is a non-fenestrated structure composed of astrocytes, pericytes, and endothelial cells which protects the brain from harmful substances ( Keaney & Campbell, 2015 ).…”