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Aims: This study aimed to analyze the potential association between cognition reserve (CR) components, including education, working activity, and leisure time activity, and cognitive function in subjects with white matter hyperintensities (WMH). The study also explored the role of the frontoparietal control network (FPCN) in such association., Methods: White matter hyperintensities subjects with and without cognitive impairment (CI) were evaluated with multimodal magnetic resonance imaging, neuropsychological testing, and CR survey. FPCN patterns were assessed with dorsolateral prefrontal cortex seed-based functional connectivity analysis., Results: Education was positively associated with cognitive function in WMH subjects with or without CI, whereas working activity and leisure time activity were positively associated with cognitive function only in those without CI. Similarly, education was associated with bilateral FPCN in both WMH groups, whereas working activity and leisure time activity were associated with bilateral FPCN mainly in the group without CI. Furthermore, FPCN partially mediated the association between education and cognitive function in both WMH groups., Conclusion: Education showed a positive impact on cognitive function in WMH subjects regardless of their cognitive status, whereas working activity and leisure time activity exhibited beneficial effects only in those without CI. The FPCN mediated the beneficial effect of education on cognitive function., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

High cognitive reserve (CR) protects against cognitive decline in individuals with white matter hyperintensities (WMH). However, the functional mechanisms remain relatively unknown. This work aimed to explore the effects of CR on the frontoparietal control network (FPCN) and cognitive function in subjects with WMH. One hundred and thirty-seven subjects with WMH and 95 control subjects without WMH underwent neuropsychological testing, CR assessments, and multimodal magnetic resonance imaging (MRI) scanning. A mixed analysis of covariance with CR level (high CR vs. low CR) and WMH status (with WMH vs. without WMH) as fixed factors was performed on the FPCN. WMH volume was negatively correlated with global cognitive function in subjects with low CR not in those with high CR, suggesting a buffering effect of high CR. An interaction between CR and WMH was detected on the right FPCN in frontal regions. Specifically, control subjects with high CR had significantly higher functional connectivity (FC) in frontal regions than control subjects with low CR, whereas this relation was inverted in WMH subjects. Correlative analyses showed positive associations of the FC with cognitive performance in both WMH subjects and control subjects, although the associations were not significant after correction for multiple comparisons. In conclusion, CR differentially regulated the FPCN in frontal regions between subjects with WMH and those without WMH. This regulation supports the flexibility of CR in regulating brain function and may underlie the effects of CR on cognitive function in WMH subjects., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer's disease (AD) spectrum patients., Objective: We recruited 16 amnesic mild cognitive impairment (aMCI) and 6 AD patients in the study. All the patients were stimulated to the left angular gyrus, which was confirmed a strong link to the hippocampus through neuroimaging studies, by the neuro-navigated rTMS for four weeks., Methods: Automated fiber quantification using diffusion tensor imaging metrics and graph theory analysis on functional network were employed to detect the neuroplasticity of brain networks., Results: After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment score of two groups were significantly improved. Increased FA values of right anterior thalamic radiation among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of thalamic system., Conclusion: We speculated that the rTMS intervention targeting left angular gyrus may be served as a strategy to improve cognitive impairment at the early stage of AD patients, supporting by the neuroplasticity of thalamic system.

Background: Impaired cerebrovascular reactivity (CVR) plays an important role in the pathophysiology of white matter hyperintensities (WMHs). The pathogenesis of CVR in the development of WMH-related cognitive impairment (CI) remains poorly understood., Purpose: To detect the CVR status in WMH subjects with/without CI by using a resting-state blood oxygenation level-dependent (BOLD) approach and to explore the mediating relationships among CVR, WMH, and cognitive level., Study Type: Prospective., Subjects: Subjects with moderate to severe WMH (with CI [WMH-CI], n = 68; without CI [WMH-no-CI, n = 63) as well as normal controls (NCs, n = 87)., Field Strength/sequence: 3.0T with gradient-recalled echoplanar imaging and 3D fluid-attenuated inversion recovery., Assessment: The CVR, WMH volume, and cognitive level were assessed. The CVR map was derived using BOLD signal obtained from resting-state functional MRI data., Statistical Tests: CVR maps were compared among the three groups. Partial correlation analyses were performed to correlate impaired CVR with WMH volume and cognitive test scores. Mediation analysis was conducted to determine whether WMH acted as a mediating factor between CVR and cognitive function., Results: Compared with the NC group, both WMH groups showed reduced CVR in the left hemisphere (P < 0.05). The WMH-CI group showed further decreased CVR in the left frontal area, when compared with the WMH-no-CI group (P < 0.05). In the WMH-CI group, the lower CVR in left frontal area was a strong indicator of poor performance on general cognition (r = 0.311), executive function (r = 0.362), and information processing speed (r = 0.399) (all P < 0.05). Periventricular WMH (PWMH) volume mediated these correlations, the β and 95% bootstrap confidence intervals were (0.5097, [0.1498,1.1385]), (-0.4081, [-1.0256,-0.1363]), and (-0.5576, [-1.4666,-0.1538]), respectively., Data Conclusion: WMH-CI subjects showed a greater reduction of CVR derived from a resting-state BOLD approach in the left frontal area than WMH-no-CI subjects. Cognition was highly dependent on the integrity of cerebrovascular reactivity and mediated by PWMH burden., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 2., (© 2020 International Society for Magnetic Resonance in Medicine.)