Abstract Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community‐dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity‐related CR (CRI‐leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI‐leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.
Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Copy DOI
We investigate the association between the intracranial pulsatility assessed by 4D-flow imaging and white matter degeneration in a community cohort. White matter free water and tissue fractional anisotropy were used to reflect white matter degeneration. We found that the intracranial arterial pulsatility in different vessel segments was positively associated with increased free water, and negatively associated with tissue fractional anisotropy. After adjusting for age and vascular risk factors, the associations disappeared. Further investigations in larger samples are warranted.
Background: The inferior frontal sulci are essential sites on the route of cerebrospinal fluid outflow. A recent study suggests that inferior frontal sulcal hyperintensities (IFSH) on FLAIR images might be related to glymphatic dysfunction. Objective: To investigate whether IFSH is associated with Alzheimer’s disease (AD) pathology and cerebral small vessel disease (SVD) burden. Methods: We retrospectively collected data from 272 non-demented subjects in the ADNI3 database. The IFSH was assessed on 3D fluid-attenuated inversion recovery images. The standardized uptake value ratios of amyloid and tau PET were used to reflect the AD pathology burden. To measure the SVD burden, we assessed white matter hyperintensities (WMH), dilation of perivascular spaces, microbleeds, and lacunes. Finally, we performed ordinal logistic regression analyses to investigate the associations between the IFSH score and AD pathology and SVD burden. Results: The IFSH score was associated with the deep WMH score (OR, 1.79; 95% CI, 1.24 – 2.59) controlling for age and sex. The association remained significant in the multivariable regression models. There was no association between the IFSH score and AD pathology burden. Conclusion: This study suggests that the IFSH sign is associated with SVD but not AD pathology. Further studies are needed to confirm the findings.
Motivation: Chronic hypoperfusion is a central mechanism of cerebral small vessel disease (CSVD), but studies using different methods have shown different results. Goal(s): To compare the associations between CSVD and CBF measured by phase-contrast MRI and ASL in the same cohort. Approach: 69 subjects were totally recruited in the study. WMH, FW, and tFA were used to reflect the disease severity. The associations between CSVD and CBF measured by two methods were investigated. Results: Compared to CBFPC, CBFASL showed a negative association with FW and a positive association with tFA. The ratio of CBFASL to CBFPC was also correlated with FW and tFA. Impact: Future studies need to consider the differences between CBF measured by ASL and phase-contrast MRI and choose a more appropriate method according to the research purpose.
Background White matter (WM) degeneration is a key feature of Alzheimer's disease (AD). However, the underlying mechanism remains unclear. Purpose To investigate how amyloid‐β (Aβ), tau, and small vascular disease (SVD) jointly affect WM degeneration in subjects along AD continuum. Study Type Retrospective. Subjects 152 non‐demented participants (age: 55.8–91.6, male/female: 66/86) from the ADNI database were included, classified into three groups using the A (Aβ)/T (tau)/N pathological scheme (Group 1: A−T−; Group 2: A+T−; Group 3: A+T+) based on positron emission tomography data. Field Strength/Sequence 3T; T1‐weighted images, T2‐weighted fluid‐attenuated inversion recovery images, T2*‐weighted images, diffusion‐weighted spin‐echo echo‐planar imaging sequence (54 diffusion directions). Assessment Free‐water diffusion model (generated parameters: free water, FW; tissue fractional anisotropy, FAt; tissue mean diffusivity, MDt); SVD total score; Neuropsychological tests. Statistical Tests Linear regression analysis was performed to investigate the independent contribution of AD (Aβ and tau) and SVD pathologies to diffusion parameters in each fiber tract, first in the entire population and then in each subgroup. We also investigated associations between diffusion parameters and cognitive functions. The level of statistical significance was set at p < 0.05 (false discovery rate corrected). Results In the entire population, we found that: 1) Increased FW was significantly associated with SVD and tau, while FAt and MDt were significantly associated with Aβ and tau; 2) The spatial pattern of fiber tracts related to a certain pathological marker is consistent with the known distribution of that pathology; 3) Subgroup analysis showed that Group 2 and 3 had more alterations of FAt and MDt associated with Aβ and tau; 4) Diffusion imaging indices showed significant associations with cognitive score in all domains except memory. Data Conclusion WM microstructural injury was associated with both AD and SVD pathologies, showing compartment‐specific, tract‐specific, and stage‐specific WM patterns. Evidence Level 1 Technical Efficacy Stage 3
Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) are significant markers associated with various neurological diseases. Although quantitative analysis of PVS may enhance sensitivity and improve consistency across studies, the field lacks a universally validated method for analyzing images from multi-center studies.
Arterial pulsation has been suggested as a key driver of paravascular cerebrospinal fluid flow, which is the foundation of glymphatic clearance. However, whether intracranial arterial pulsatility is associated with glymphatic markers in humans has not yet been studied. Seventy-three community participants were enrolled in the study. 4D phase-contrast magnetic resonance imaging (MRI) was used to quantify the hemodynamic parameters including flow pulsatility index (PIflow) and area pulsatility index (PIarea) from 13 major intracerebral arterial segments. Three presumed neuroimaging markers of the glymphatic system were measured: including dilation of perivascular space (PVS), diffusivity along the perivascular space (ALPS), and volume fraction of free water (FW) in white matter. We explored the relationships between PIarea, PIflow, and the presumed glymphatic markers, controlling for related covariates. PIflow in the internal carotid artery (ICA) C2 segment (OR, 1.05; 95% CI, 1.01-1.10, per 0.01 increase in PI) and C4 segment (OR, 1.05; 95% CI, 1.01-1.09) was positively associated with the dilation of basal ganglia PVS, and PIflow in the ICA C4 segment (OR, 1.06, 95% CI, 1.02-1.10) was correlated with the dilation of PVS in the white matter. ALPS was associated with PIflow in the basilar artery (β, -0.273, p, 0.046) and PIarea in the ICA C2 (β, -0.239, p, 0.041) and C7 segments (β, -0.238, p, 0.037). Intracranial arterial pulsatility was associated with presumed neuroimaging markers of the glymphatic system, but the results were not consistent across different markers. Further studies are warranted to confirm these findings.
Vascular degeneration is an important cause of brain damage in aging. Assessing the functional properties of the cerebral vascular system may aid early diagnosis and prevention.
White matter (WM) free water (FW) is a potential imaging marker for cerebral small vessel disease (CSVD). This study aimed to characterize longitudinal changes in WM FW and investigate factors contributing to its elevation in CSVD. We included 80 CSVD patients and 40 normal controls (NCs) with multi-modality MRI data. Cerebral blood flow (CBF) was measured, and fiber alterations were assessed using total apparent fiber density (AFD
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(144 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(216 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(288 450 300)'/%3e%3c/svg%3e)