Interplay of White Matter Hyperintensities, Cerebral Networks, and                    Cognitive Function in an Adult Population: Diffusion-Tensor Imaging in the                    Maastricht Study

Vergoossen, Laura; Jansen, Jacobus F. A.; Sloten, Thomas T. van; Stehouwer, Coen D. A.; Schaper, Nicolaas C.; Wesselius, Anke; Dagnelie, Pieter C.; Köhler, Sebastian; Boxtel, M.P.J. van; Kroon, Abraham A.; Jong, Joost J.A. de; Schram, Miranda T.; Backes, Walter H.

doi:10.1148/radiol.2021202634

Cited by 34 publications

(47 citation statements)

References 33 publications

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“…Previous studies on SVD have demonstrated that alterations in the structural network organization (i.e., reduced global and local efficiency) are associated with the MRI markers for SVD (i.e., WMHs, cerebral lacunar infarcts, and microbleeds), and topological disorganization mediates the relationship between MRI markers and cognition in SVD ( Lawrence et al, 2014 ; Tuladhar et al, 2016 ). Furthermore, a recent clinical study suggested that WMH volumes, structural connectivity measures (i.e., local network efficiency), and information processing speed were interrelated, and the relationship between WMHs and information processing speed was mediated by the local network efficiency ( Vergoossen et al, 2021 ). In addition, emerging literatures on SVD reported that network efficiency could mediate the associations between cerebral vascular lesions and cognitive function, which shed light on the importance of connectome-based analyses in understanding the precise underlying topological mechanism of cognitive decrements in SVD ( Du et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is a relative labeling technique that comprises differently sized brain regions that may influence the network properties ( Zalesky et al, 2010 ). Using alternative techniques such as functional activations or high-resolution random parcellation to define nodes may provide a more interpretable solution ( Fornito et al, 2013 ; Vergoossen et al, 2021 ). Furthermore, in this study, we focused on the WM changes in ILA patients.…”

Section: Discussionmentioning

confidence: 99%

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Disrupted Structural Brain Connectome Is Related to Cognitive Impairment in Patients With Ischemic Leukoaraiosis

Lü

Wang

Cui

et al. 2021

Front. Hum. Neurosci.

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Ischemic leukoaraiosis (ILA) is related to cognitive impairment and vascular dementia in the elderly. One possible mechanism could be the disruption of white matter (WM) tracts and network function that connect distributed brain regions involved in cognition. The purpose of this study was to investigate the relationship between structural connectome and cognitive functions in ILA patients. A total of 89 patients with ILA (Fazekas score ≥ 3) and 90 healthy controls (HCs) underwent comprehensive neuropsychological examinations and diffusion tensor imaging scans. The tract-based spatial statistics approach was employed to investigate the WM integrity. Graph theoretical analysis was further applied to construct the topological architecture of the structural connectome in ILA patients. Partial correlation analysis was used to investigate the relationships between network measures and cognitive performances in the ILA group. Compared with HCs, the ILA patients showed widespread WM integrity disruptions. The ILA group displayed increased characteristic path length (Lp) and decreased global network efficiency at the level of the whole brain relative to HCs, and reduced nodal efficiencies, predominantly in the frontal–subcortical and limbic system regions. Furthermore, these structural connectomic alterations were associated with cognitive impairment in ILA patients. The association between WM changes (i.e., fractional anisotropy and mean diffusivity measures) and cognitive function was mediated by the structural connectivity measures (i.e., local network efficiency and Lp). In conclusion, cognitive impairment in ILA patients is related to microstructural disruption of multiple WM fibers and topological disorganization of structural networks, which have implications in understanding the relationship between ILA and the possible attendant cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disrupted Structural Brain Connectome Is Related to Cognitive Impairment in Patients With Ischemic Leukoaraiosis

Lü

Wang

Cui

et al. 2021

Front. Hum. Neurosci.

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“…Conventional diffusion measures (e.g., FA, MD) (Michael O'Sullivan et al, 2004;O'Sullivan et al, 2005;Nitkunan et al, 2008;Schmidt et al, 2010;Quinque et al, 2012;Lawrence et al, 2013;Tuladhar et al, 2015;Baykara et al, 2016;Moonen et al, 2017;Zeestraten et al, 2017;Tozer et al, 2018;Chen et al, 2019;Wei et al, 2019;Huang et al, 2020;Liu et al, 2020;Du et al, 2021;Vergoossen et al, 2021) Advanced diffusion measures (e.g. FW, NODDI, DKI, IVIM) (Zhang, Wong, van de Haar, et al, 2017;Duering et al, 2018;Gesierich et al, 2020;Konieczny et al, 2021) Structural network measures (Lawrence et al, 2014;Reijmer et al, 2016;Tuladhar et al, 2016Tuladhar et al, , 2017Heinen et al, 2018;van Leijsen et al, 2019;Boot et al, 2020;Gesierich et al, 2020;Liu et al, 2020;Du et al, 2021) Study findings: White matter regions related to cognitive performance in CSVD…”

Section: Csvd Dmri Study Methodologymentioning

confidence: 99%

“…However, despite the well-known decline in processing speed (Prins et al ., 2005; Peng, Geriatric Neurology Group, Chinese Society of Geriatrics and Clinical Practice Guideline for Cognitive Impairment of Cerebral Small Vessel Disease Writing Group, 2019; O. K. L. Hamilton et al ., 2021), which is associated with widespread white matter changes in CSVD (Konieczny et al ., 2021; Vergoossen et al ., 2021), the abnormalities in the SWM are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Superficial white matter microstructure affects processing speed in cerebral small vessel disease

Wang

Zhang

Huang

et al. 2022

Preprint

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White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD). This condition contributes to about 50% of dementias worldwide, a massive health burden in aging. Microstructural alterations in the deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in the superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In this paper, 141 patients with CSVD were studied. Processing speed was assessed by the completion time of the Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (lesion volume on T2-FLAIR) and diffusion MRI, including DTI and free-water (FW) imaging microstructure measures. The results of our study indicate that the superficial white matter may play a particularly important role in cognitive decline in CSVD. SWM imaging measures resulted in a large contribution to processing speed, despite a relatively small WMH burden in the SWM. SWM FW had the strongest association with processing speed among all imaging markers and, unlike the other diffusion MRI measures, significantly increased between two patient subgroups with the lowest WMH burdens (possibly representing early stages of disease). When comparing two patient subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Given significant effects of WMH volume and regional FW on processing speed, we performed a mediation analysis. SWM FW was found to fully mediate the association between WMH volume and processing speed, while no mediation effect of DWM FW was observed. Overall, our findings identify SWM abnormalities in CSVD and suggest that the SWM has an important contribution to processing speed. Results indicate that FW in the SWM is a sensitive marker of microstructural changes associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes in future research.

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Cognitive resilience depends on white matter connectivity: The Maastricht Study

DeJong

Jansen

Boxtel

et al. 2022

Alzheimer's & Dementia

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Introduction: Differences in brain network connectivity may reflect the capability of the neurological substrate to compensate for brain damage and preserve cognitive function (cognitive reserve). We examined the associations between white matter connectivity, brain damage markers, and cognition in a population sample of middle-aged individuals.Methods: A total of 4759 participants from The Maastricht Study (mean age = 59.2, SD = 8.7, 50.2% male) underwent cognitive testing and diffusion magnetic resonance imaging (dMRI), from which brain volume, structural connectivity, and vascular damage were quantified. Multivariable linear regression was used to investigate whether connectivity modified the association between brain damage and cognition, adjusted for demographic and cardiometabolic risk factors.

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Interplay of White Matter Hyperintensities, Cerebral Networks, and Cognitive Function in an Adult Population: Diffusion-Tensor Imaging in the Maastricht Study

Cited by 34 publications

References 33 publications

Disrupted Structural Brain Connectome Is Related to Cognitive Impairment in Patients With Ischemic Leukoaraiosis

Disrupted Structural Brain Connectome Is Related to Cognitive Impairment in Patients With Ischemic Leukoaraiosis

Superficial white matter microstructure affects processing speed in cerebral small vessel disease

Cognitive resilience depends on white matter connectivity: The Maastricht Study

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