Abstract
AimsThis study aimed to investigate the relationships of impaired cerebrovascular reactivity (CVR) and abnormal functional connectivity (FC) with white matter hyperintensity (WMH)-related cognitive decline.MethodsA total of 233 WMH subjects were recruited and categorized into WMH-I (n = 106), WMH-II (n = 72), and WMH-III (n = 55) groups according to Fazekas visual rating scale. All participants underwent neuropsychological tests and multimodal MRI scans, including 3D-T1, and resting-state functional magnetic resonance imaging (rs-fMRI). The alterations of CVR maps and FC were further explored.ResultsSubjects with a higher WMH burden displayed a lower CVR in the left medial occipital gyrus (MOG). The FC analysis using MOG as a seed revealed that the FC of the left insula, left inferior parietal lobule, and thalamus changed abnormally as WMH aggravated. After adjusting for age, gender, and education years, the serial mediation analysis revealed that periventricular white matter hyperintensity contributes indirectly to poorer Mini-Mental State Examination (MMSE) scores (indirect effect: β = −0.1248, 95% CI: −0.4689, −0188), poorer Montreal Cognitive Assessment (MoCA) (indirect effect: β = −0.1436, 95% CI: −0.4584, −0.0292) scores, and longer trail making tests A (TMT-A) (indirect effect: β = 0.1837, 95% CI: 0.0069, 0.8273) times, specifically due to the lower CVR of the left MOG and the higher FC of the left insula-MOG.ConclusionThe CVR decline of the left MOG and the abnormal FC of the left insula-MOG attributed to WMH progression were responsible for the poor general cognition (MMSE and MoCA) and information processing speed (TMT-A). The left MOG may act as a connection, which is involved in the processing of cognitive biases by connecting with the left insula-cortical regions in WMH individuals.
Highlights
White matter hyperintensity (WMH), presented as hyperintensity of the subcortical white matter on T2-weighted image or fluid-attenuated inversion recovery (FLAIR) sequence, is frequently observed in the brain of elderly individuals (Alber et al, 2019)
We found that moderate–severe-WMH individuals displayed a lower cerebrovascular reactivity (CVR) in the left middle occipital gyrus (MOG) than mild-WMH individuals, and the decreased CVR was associated with general cognition (MoCA), information processing speed (SCWT-A and Trail Making Test (TMT)-A), and executive function (SCWT-C) in severe-WMH individuals
We found that the functional connectivity (FC) of the left insula-MOG was positively associated with general cognition (MMSE and Montreal Cognitive Assessment (MoCA)) and information processing speed (SCWT-A and TMT-A)
Summary
White matter hyperintensity (WMH), presented as hyperintensity of the subcortical white matter on T2-weighted image or fluid-attenuated inversion recovery (FLAIR) sequence, is frequently observed in the brain of elderly individuals (Alber et al, 2019). Epidemiologic studies revealed that WMH can be observed in 72–96% of European individuals over 60 years old (Longstreth et al, 1996) and 70% Chinese individuals over 50 years old (Han et al, 2018). Increasing evidences have revealed that the WMH burden exerts a negative impact on cognition, mainly in executive function and information process speed (Debette and Markus, 2010; Jiang et al, 2018; Alber et al, 2019). Severe WMH is closely related to incidence rates of stroke, dementia, and death (Debette and Markus, 2010; Prins and Scheltens, 2015). The underlying mechanisms by which increasing WMH burden triggers cognitive impairment and vascular events remain largely unknown. A better understanding of the mechanisms linking WMH with cognitive decline is of utmost importance
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