Frontiers in Aging Neuroscience最新文献

{"title":"Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice.","authors":"Yarong Wang, Rongxing Zhang, Yumin Jiang, Jingwen Liao, Lianwei Mu, Min Hu","doi":"10.3389/fnagi.2024.1489214","DOIUrl":"10.3389/fnagi.2024.1489214","url":null,"abstract":"<p><strong>Objective: </strong>Anxiety and depression-like symptoms occur in the early stages of Alzheimer's disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms.</p><p><strong>Methods: </strong>After eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer's disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis.</p><p><strong>Results: </strong>We first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice.</p><p><strong>Conclusion: </strong>These findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1489214"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of cardiovascular health with cognitive function and the mediating effect of depressive state.","authors":"Yiwei Hu, Xuelu Sun, Chen Guo, Ruiyun Wu, Jiahao Dou, Shoufang Song, Fanshun Guo, Jin Wei","doi":"10.3389/fnagi.2024.1465310","DOIUrl":"10.3389/fnagi.2024.1465310","url":null,"abstract":"<p><strong>Background: </strong>Although previous research has substantiated lifestyle and cardiovascular-related measures have some impact on cognitive function, studies focusing on the correlation between Life's Essential 8 (LE8), an indicator for quantifying cardiovascular health (CVH), and cognitive function are limited. Consequently, this study sought to explore the potential link between CVH and cognitive function as well as to determine if depressive states mediated the relationship.</p><p><strong>Methods: </strong>A total of 2,263 individuals were selected from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Post-averaged LE8 scores was classified as low CVH (0-49), moderate CVH (50-79), and high CVH (80-100) according to the American Heart Association (AHA). Cognitive function was evaluated using the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), the instant recall test (IRT), and the delayed recall test (DRT). The Z-score is figured by subtracting the average of the scores of four test sections and dividing by the standard deviation. Models of multi-variable linear regression were employed to appraise the relationships between CVH and the Z-score for cognitive function. Depression was assessed through the utilization of the Patient Health Questionnaire (PHQ-9). Points of 10 or above indicated a positive diagnosis. Weighted linear regression and restricted cubic spline (RCS) were employed to evaluate the correlation between CVH and cognitive function. Pearson's test was utilized to explore the interrelation among primary variables and mediated effects analyses of depressive states.</p><p><strong>Results: </strong>A significant positive linear relationship was observed between LE8 score and cognitive function Z-score. In all models, there was a positive correlation between higher Z-score for cognitive function and every ten points added to the LE8 score, which evaluates CVH. The findings of the mediating effect study indicated that the effects of cardiovascular health on cognitive function were partially mediated by depression.</p><p><strong>Conclusion: </strong>Results showed a meaningful positive linear correlation between the level of CVH and cognitive function, with a mediating role for depression. These results accentuate the significance of sustaining high CVH and avoiding depression to improve cognitive functioning.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1465310"},"PeriodicalIF":4.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blue light-induced phototoxicity in retinal cells: implications in age-related macular degeneration.","authors":"Harshini Chakravarthy, Vasil Georgyev, Cole Wagen, Amir Hosseini, Joanne Matsubara","doi":"10.3389/fnagi.2024.1509434","DOIUrl":"10.3389/fnagi.2024.1509434","url":null,"abstract":"<p><p>Sunlight exposure is recognized as a risk factor for the development of age-related macular degeneration (AMD), a common neurodegenerative retinal disease in the elderly. Specifically, the blue light wavelengths within sunlight can negatively impact the physiology of light-sensitive retinal cells, including retinal pigmented epithelium (RPE) and photoreceptors. This review explores blue light-induced retinal degeneration, emphasizing the structural and functional impairments in RPE. The initial section provides a brief overview of blue light's effects on photoreceptors, followed by a comprehensive analysis of its detrimental impact on RPE. <i>In vitro</i> studies reveal that blue light exposure induces morphological alterations and functional impairments in RPE, including reduced phagocytic activity, disrupted secretion of neurotrophic factors, and compromised barrier function. Mechanisms of retinal damage, including oxidative stress, inflammation, lipofuscin accumulation, mitochondrial dysfunction and ER stress in RPE, are also explored. The strengths and limitations of <i>in vitro</i>, animal and <i>ex vivo</i> models for studying blue light exposure are discussed, with recommendations for improving reproducibility in future studies.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1509434"},"PeriodicalIF":4.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction and Alzheimer's disease: pathogenesis of mitochondrial transfer.","authors":"Yun Wei, Xinlei Du, Hongling Guo, Jingjing Han, Meixia Liu","doi":"10.3389/fnagi.2024.1517965","DOIUrl":"10.3389/fnagi.2024.1517965","url":null,"abstract":"<p><p>In recent years, mitochondrial transfer has emerged as a universal phenomenon intertwined with various systemic physiological and pathological processes. Alzheimer's disease (AD) is a multifactorial disease, with mitochondrial dysfunction at its core. Although numerous studies have found evidence of mitochondrial transfer in AD models, the precise mechanisms remain unclear. Recent studies have revealed the dynamic transfer of mitochondria in Alzheimer's disease, not only between nerve cells and glial cells, but also between nerve cells and glial cells. In this review, we explore the pathways and mechanisms of mitochondrial transfer in Alzheimer's disease and how these transfer activities contribute to disease progression.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1517965"},"PeriodicalIF":4.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Immediate modulatory effects of transcutaneous vagus nerve stimulation on patients with Parkinson's disease: a crossover self-controlled fMRI study.","authors":"Chengwei Fu, Xiaoyan Hou, Chunye Zheng, Yue Zhang, Zhijie Gao, Zhaoxian Yan, Yongsong Ye, Bo Liu","doi":"10.3389/fnagi.2024.1538891","DOIUrl":"10.3389/fnagi.2024.1538891","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnagi.2024.1444703.].</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1538891"},"PeriodicalIF":4.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of heart rate variability as a screening tool for mild neurocognitive disorder.","authors":"Julia Czopek-Rowinska, Eling D de Bruin, Patrick Manser","doi":"10.3389/fnagi.2024.1498687","DOIUrl":"10.3389/fnagi.2024.1498687","url":null,"abstract":"<p><strong>Background: </strong>Mild neurocognitive disorder (mNCD) is recognized as an early stage of dementia and is gaining attention as a significant healthcare problem due to current demographic changes and increasing numbers of patients. Timely detection of mNCD provides an opportunity for early interventions that can potentially slow down or prevent cognitive decline. Heart rate variability (HRV) may be a promising measure, as it has been shown to be sensitive to cognitive impairment. However, there is currently no evidence regarding the diagnostic accuracy of HRV measurements in the context of the mNCD population. This study aimed to evaluate the diagnostic accuracy of vagally-mediated HRV (vm-HRV) as a screening tool for mNCD and to investigate the relationship between vm-HRV with executive functioning and depression in older adults who have mNCD.</p><p><strong>Methods: </strong>We retrospectively analyzed data from healthy older adults (HOA) and individuals with a clinical diagnosis of mNCD with a biomarker-supported characterization of the etiology of mNCD. Diagnostic accuracy was evaluated using receiver operating characteristic curve analysis based on the area under the curve. Sensitivity and specificity were calculated based on the optimal threshold provided by Youden's Index. Multiple linear regression analyses were conducted to investigate the relationship between vm-HRV and executive functioning and depression.</p><p><strong>Results: </strong>This analysis included 42 HOA and 29 individuals with mNCD. The relative power of high frequency was found to be increased in individuals with mNCD. The greatest AUC calculated was 0.68 (with 95% CI: 0.56, 0.81) for the relative power of high frequency. AUCs for other vm-HRV parameters were between 0.53 and 0.61. No consistent correlations were found between vm-HRV and executive functioning or depression.</p><p><strong>Conclusion: </strong>It appears that vm-HRV parameters alone are insufficient to reliably distinguish between HOA and older adults with mNCD. Additionally, the relationship between vm-HRV and executive functioning remains unclear and requires further investigation. Prospective studies that encompass a broad range of neurocognitive disorders, HRV measurements, neuroimaging, and multimodal approaches that consider a variety of functional domains affected in mNCD are warranted to further investigate the potential of vm-HRV as part of a multimodal screening tool for mNCD. These multimodal measures have the potential to improve the early detection of mNCD in the future.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1498687"},"PeriodicalIF":4.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The study on cuproptosis in Alzheimer's disease based on the cuproptosis key gene <i>FDX1</i>.","authors":"Guilin Chen, Erwei Xi, Xiaozhen Gu, Huili Wang, Qiqiang Tang","doi":"10.3389/fnagi.2024.1480332","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1480332","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and cognitive impairments. Previous studies have shown neuronal death in the brains of AD patients, but the role of cuproptosis and its associated genes in AD neurons remains unclear.</p><p><strong>Methods: </strong>Intersection analysis was conducted using the AD transcriptome dataset GSE63060, neuron dataset GSE147528, and reported cuproptosis-related genes to identify the cuproptosis key gene <i>FDX1</i> highly expressed in AD. Subsequently, cell experiments were performed by treating SH-SY5Y cells with Aβ_25-35 to establish AD cell model. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blotting (WB) assays were employed to detect the expression levels of <i>FDX1</i>, <i>DLAT</i>, and <i>DLST</i>. Cell proliferation was analyzed by counting Kit-8 (CCK8), mitochondrial ROS levels were analyzed using flow cytometry. shRNA was used to downregulate <i>FDX1</i> expression, followed by repetition of the aforementioned experiments. Clinical experiments utilized qPCR to detect <i>FDX1</i> mRNA levels in peripheral venous blood of patients, and analyzed <i>FDX1</i> expression differences in different <i>APOE</i> genotypes of AD patients. Finally, a protein-protein interaction (PPI) network of <i>FDX1</i> was constructed based on the GeneMANIA database, immune infiltration analysis was conducted using R language, and transcription factors prediction for <i>FDX1</i> was performed based on the ENCODE database.</p><p><strong>Results: </strong>The cuproptosis key gene <i>FDX1</i> showed significantly higher expression in peripheral blood and neuron models of AD compared to non-AD individuals, with significantly higher expression in <i>APOE ε4/ε4</i> genotype than other <i>APOE</i> genotype of AD patients. Knockdown of <i>FDX1</i> expression reduced the lipidation levels of <i>DLAT</i> and <i>DLST</i> in neurons, alleviated ROS accumulation in mitochondria, improved cell viability, and mitigated cuproptosis. Immune infiltration analysis results indicated a high enrichment of peripheral blood γδ-T lymphocytes in AD, and <i>FDX1</i> was significantly associated with the infiltration of four immune cells and may be regulated by three transcription factors.</p><p><strong>Conclusion: </strong>The cuproptosis key gene <i>FDX1</i> is highly expressed in AD and may promote cuproptosis in AD neurons by regulating the lipidation levels of <i>DLAT</i> and <i>DLST</i>, thereby participating in the onset and development of AD. This provides a potential target for the diagnosis and treatment of AD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1480332"},"PeriodicalIF":4.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered brain glymphatic function on diffusion-tensor MRI in patients with spontaneous intracerebral hemorrhage: an exploratory study.","authors":"Xiaona Xia, Qingguo Ren, Juntao Zhang, Shuai Guan, Qingjun Jiang, Ying Wei, Rui Hua, Shen Zhao, Xiangjun Hu, Feng Shi, Xiangshui Meng","doi":"10.3389/fnagi.2024.1506980","DOIUrl":"10.3389/fnagi.2024.1506980","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the function of the glymphatic system (GS) and its association with neuropsychological tests in spontaneous intracerebral hemorrhage (sICH) by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS).</p><p><strong>Methods: </strong>This retrospective study included 58 patients with sICH and 63 age- and sex-matched healthy controls (HCs). Partial correlation analyses were performed to examine the relationships between the DTI-ALPS index and radiological as well as clinical data. Mediation analyses were performed to explore the mediating role of the grey matter proportion (GM%) in the relationship between DTI-ALPS index and Montreal Cognitive Assessment (MoCA) score.</p><p><strong>Results: </strong>Significantly lower DTI-ALPS index values were observed in sICH compared with HCs (FDR-<i>p</i> < 0.001). In the acute-subacute sICH group, the ALPS index was significantly correlated with hematoma volume (<i>r</i> = -0.572, FDR-<i>p</i> = 0.031). In the chronic sICH group, the ALPS index was significantly correlated with MoCA scores (<i>r</i> = 0.425, FDR-<i>p</i> = 0.014). In chronic sICH groups, GM% served as a significant mediator in the relationship between the DTI-ALPS index and MoCA scores (indirect effects <i>β</i> = 4.925, 95%CI: 0.028, 11.841). The ALPS index was identified as an independent prognostic indicator for unfavorable outcomes in sICH (<i>β</i> = -9.851, <i>p</i> = 0.018).</p><p><strong>Conclusion: </strong>Our study demonstrated that the DTI-ALPS index decreased in sICH patients, suggesting potential functional impairment of the lymphoid system. Additionally, the DTI-ALPS index served as an independent predictor of poor 90-day prognosis. In the acute-subacute stage of sICH, the DTI-ALPS index had negative correlation with hematoma volume. In the chronic sICH group, the GM% partially mediated the relationship between the GS and cognitive function.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1506980"},"PeriodicalIF":4.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aftereffect of single transcranial direct and alternating current stimulation on spontaneous home-cage and open-field EEG activities in a mouse model of Alzheimer's disease.","authors":"Huaying Sun, Yumei Wang, Dong Yuan, Mengsi Duan, Zhuangfei Chen, Yu Fu","doi":"10.3389/fnagi.2024.1492838","DOIUrl":"10.3389/fnagi.2024.1492838","url":null,"abstract":"<p><strong>Background: </strong>As a non drug and non invasive therapy, both transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) may modulate cortical rhythms and serve as potentially effective approaches to cognitive decline in Alzheimer's disease (AD). However, studies using animal models of AD are quite limited.</p><p><strong>Methods: </strong>This study investigates the aftereffects of tACS and tDCS on brain EEG activity and associated exploratory behavior in normal aged and APP/PS1 transgenic mice (15 months old). Anodal tDCS and 10 Hz tACS (350 μA, 20 min) were applied once and EEGs were recorded from the hippocampus (Hip) and prefrontal cortex (PFC) during spontaneous home-cage state and open-field exploration.</p><p><strong>Results: </strong>A key finding was that tDCS induced significant alpha (8-12 Hz) EEG changes while tACS induced peak frequency changes in the group difference between normal aged and AD mice. However, both groups showed similar increases in theta (4-8 Hz) EEG activity during open-field exploration and increases in gamma (20-100 Hz) EEG activity in spontaneous state, suggesting that the ongoing physiological state may be related to some of the EEG changes.</p><p><strong>Conclusion: </strong>This study provides insight into the short-term aftereffects of transcranial current stimulation in the aging and AD brain and is the first animal study to compare brain activity between tACS and tDCS treatments.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1492838"},"PeriodicalIF":4.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mitochondrial function of peripheral blood cells in cognitive frailty patients.","authors":"Li Qin, Tingting Huang, Danmei Zhang, Liqin Wei, Guochao Li, Qianqian Zhu, Qiangwei Tong, Guoxian Ding, Juan Liu","doi":"10.3389/fnagi.2024.1503246","DOIUrl":"10.3389/fnagi.2024.1503246","url":null,"abstract":"<p><strong>Background: </strong>Cognitive frailty (<i>CF</i>), characterized by the coexistence of physical frailty and cognitive impairment, is linked to increased morbidity and mortality in older adults. While <i>CF</i> has been linked to multiple physiological and lifestyle factors, the underlying biological mechanisms remain poorly understood. This study investigated the risk factors for <i>CF</i> and explored the relationship between mitochondrial function and <i>CF</i> in hospitalized patients.</p><p><strong>Methods: </strong>A total of 279 hospitalized individuals were recruited from December 2020 to August 2022, conducted comprehensive clinical assessments, and collected peripheral blood samples. <i>CF</i> was evaluated using the Physical Frailty Phenotype and Montreal Cognitive Assessment scales. Nutritional status was assessed with the Mini Nutritional Assessment, and depression was measured using the Geriatric Depression Scale. DNA was obtained from the peripheral blood and interrogated for mitochondrial DNA copy number (mtDNAcn). Peripheral blood mononuclear cells isolated from peripheral blood were examined for respiratory function and reactive oxygen species (ROS) levels. Additionally, plasma samples were analyzed for inflammatory markers and Carnitine Palmitoyltransferase II (CPT2).</p><p><strong>Results: </strong>Among the participants, 90 were classified as <i>CF</i> and 46 as non-<i>CF.</i> Logistic regression analysis revealed that increased age (OR 1.156, 95% CI 1.064-1.255), lower educational attainment (OR 0.115, 95% CI 0.024-0.550), malnutrition (OR 0.713, 95% CI 0.522-0.973), and higher depression scores (OR 1.345, 95% CI 1.065-1.699) were significantly associated with <i>CF.</i> The independent t tests and Mann-Whitney U tests showed the <i>CF</i> group exhibited impaired mitochondrial function, characterized by reduced mtDNAcn and respiratory activity, coupled with elevated ROS, interleukin-6, and CPT2 levels compared with the non-<i>CF</i> group. After adjusted for age, sex, and BMI, compared with non-<i>CF</i> group, the OR values for the <i>CF</i> group of mtDNAcn and ROS were 0.234 (95% CI = 0.065-0.849) (<i>p</i> = 0.027) and 1.203 (95% CI = 1.075-1.347) (<i>p</i> = 0.001), respectively. The Sensitive analysis showed that the area under curve values for mtDNAcn and ROS were 0.653 and 0.925.</p><p><strong>Conclusion: </strong>Age, lower educational attainment, malnutrition, and depression are significant risk factors for CF. Moreover, mitochondrial dysfunction, characterized by decreased mtDNAcn, impaired respiratory function and increased ROS levels appears to be a critical phenotype of <i>CF.</i></p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"16 ","pages":"1503246"},"PeriodicalIF":4.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}