Effects of White Matter Hyperintensities on Verbal Fluency in Healthy Older Adults and MCI/AD

Kaskikallio, Alar; Karrasch, Mira; Koikkalainen, Juha; Lötjönen, Jyrki; Rinne, Juha O.; Tuokkola, Terhi; Parkkola, Riitta; Grönholm-Nyman, Petra

doi:10.3389/fnagi.2021.614809

Cited by 3 publications

(2 citation statements)

References 91 publications

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“…As a high-risk state for developing AD, MCI is also characterized by histopathological changes of the brain, impaired cholinergic system, Aβ deposition, cerebrovascular changes, and age-related deterioration of learning and memory but does not affect daily life [7]. Previous studies suggested that "middle-aged" SAMP8 mice were a suitable model for basic MCI research.…”

Section: Discussionmentioning

confidence: 99%

“…SAMP8 is a spontaneous animal model characterized by age-associated pathologies in the hippocampus and other brain regions, including Aβ deposits, tau hyperphosphorylation, inflammation, endoplasmic reticulum stress, and neuronal injury [7]. Since all these changes resemble AD pathology, SAMP8 mice can be used as models for studying cognitive decline with aging.…”

Section: Introductionmentioning

confidence: 99%

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Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice

Zhang,

Sun,

et al. 2023

Mediators of Inflammation

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Background. Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer’s disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods. MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl’s/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results. It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion. JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice

Zhang,

Sun,

et al. 2023

Mediators of Inflammation

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Effects of Remote Expressive Arts Program in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial

Luo

Lin

Yan

et al. 2023

JAD

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Background: Mild cognitive impairment (MCI) is a stage of cognitive ability loss with intact activities of daily living and an increased risk for the development of dementia. Objective: This study evaluated the intervention effect of remote expressive arts program (rEAP) on cognitive function in older adults with MCI and investigated the underlying neurobiological mechanisms. Methods: We assigned 73 older MCI patients to receive rEAP or health education (HE), who underwent neuropsychological evaluation and resting-state functional magnetic resonance imaging before and after treatment. Neuropsychological scores were analyzed using SPSS software, and regional homogeneity (ReHo) values and seed-based functional connectivity (FC) were analyzed using Matlab software. Results: The rEAP group showed more significant improvements in cognitive function than the HE group. rEAP affected spontaneous brain activity and brain networks. The ReHo values in the right anterior cingulate/paracingulate cortex and the left dorsolateral superior frontal gyrus significantly increased and decreased, respectively, in the rEAP and HE groups. Further, ReHo value changes were significantly associated with the corresponding neuropsychological test score changes in the rEAP group. Moreover, the rEAP group showed decreased FC between the posterior cingulate cortex and the right middle temporal gyrus and increased FC between the ventromedial prefrontal cortex and left angular gyrus. Conclusion: The 12-week rEAP improved cognitive function in MCI patients. Additionally, the alterations of spontaneous brain network connections and activity helped improve and maintain cognitive function in MCI patients.

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Decreased Hemodynamic Responses in Left Parietal Lobule and Left Inferior Parietal Lobule in Older Adults with Mild Cognitive Impairment: A Near-Infrared Spectroscopy Study

Tian

Wang

et al. 2022

JAD

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Background: The brain activation patterns of mild cognitive impairment (MCI) are still unclear and they involve multiple brain regions. Most previous studies have focused on abnormal activation in the frontal and temporal lobes, with few investigating the entire brain. Objective: To identify and compare the changes in cerebral hemodynamics and abnormal activation patterns in the entire brain of MCI patients and healthy older adults. Methods: Patients with MCI (n = 22) and healthy controls (HC, n = 34) matched by age, education levels, sex, and mental state were enrolled. They performed the same letter and category verbal fluency test (VFT) tasks while their behavioral performance and global cerebral hemodynamics were analyzed. Results: The performance during the category VFT task was significantly better than that during the letter VFT task across all participants (HC: correct: p < 0.001; intrusions: p < 0.001; MCI: correct: p < 0.001; intrusions: p < 0.001). The number of correct words during the letter and category VFT tasks was significantly higher in the HC group than in the MCI group (p < 0.001). The deoxygenated-hemoglobin (HbR) concentrations in the left parietal lobule (p = 0.0352) and left inferior parietal lobule (p = 0.0314) were significantly different during the category VFT task. Conclusion: The differences between HC and MCI groups were greater in the category task. The HbR concentration was more sensitive for the category VFT task and concentration changes in the left parietal lobule and left inferior parietal lobule may be useful for clinical screening and application; thus, they deserve more attention.

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Effects of White Matter Hyperintensities on Verbal Fluency in Healthy Older Adults and MCI/AD

Cited by 3 publications

References 91 publications

Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice

Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice

Effects of Remote Expressive Arts Program in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial

Decreased Hemodynamic Responses in Left Parietal Lobule and Left Inferior Parietal Lobule in Older Adults with Mild Cognitive Impairment: A Near-Infrared Spectroscopy Study

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