Frontiers in Aging Neuroscience最新文献

Objective: This study aimed to evaluate the efficacy of video-game-based interventions in enhancing global cognitive function and executive functioning among individuals with mild cognitive impairment (MCI).

Methods: A systematic search was conducted across PubMed, Web of Science, The Cochrane Library, Embase, CINAHL, and Medline, covering all publications available up to October 12, 2025. Meta-analyses were performed using Review Manager 5.3 and Stata 17.

Results: Five randomized controlled trials were ultimately included, comprising approximately 215 participants. Meta-analytic findings revealed that, compared with control conditions, video-game interventions significantly improved global cognition, reflected by increases in Montreal Cognitive Assessment (MoCA) scores (MD = 2.58, 95% CI: 1.27-3.90, P < 0.0001) and Mini-Mental State Examination (MMSE) scores (MD = 1.80, 95% CI: 0.79-2.80, P = 0.0005). Executive function and attentional performance also showed marked enhancement, evidenced by substantial reductions in completion time on the Trail Making Test A (TMT-A) (SMD = -1.38, 95% CI: -1.73 to -1.04, P < 0.00001) and Trail Making Test B (TMT-B) (SMD = -3.50, 95% CI: -6.03 to -0.98, P = 0.007).

Conclusion: Video-game-based interventions appear to meaningfully enhance both global cognitive function and executive functioning in individuals with MCI. However, the limited number of included studies underscores the need for future research to establish standardized intervention protocols and incorporate extended longitudinal follow-up.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024539189, identifier: CRD42024539189.

Background: Vascular cognitive impairment (VCI) is a group of cognitive disorders caused by cerebrovascular disease and is the second leading cause of dementia. VCI prevalence has significantly increased over the past decade. However, the molecular mechanisms underlying VCI remain unclear.

Objective: This review summarizes recent reports on the critical roles of hippocampal synaptic plasticity and epigenetic changes in VCI and vascular dementia (VaD) by incorporating findings from neuroimaging and molecular biology.

Methods: We reviewed studies employing molecular, electrophysiological, and neuroimaging approaches, conducted over the last two decades. Key targets of investigation included cerebral blood flow regulation, synaptic transmission, and epigenetic mechanisms such as DNA methylation, histone modification, and noncoding RNA regulation.

Results: Growing evidence suggests that chronic cerebral hypoperfusion and microvascular injury cause deficits in hippocampal synaptic plasticity, leading to long-term potentiation and memory formation deficits. Aberrant epigenetic changes, such as dysregulated DNA methylation, histone acetylation, and miRNA expression, contribute to neuroinflammatory and neurodegenerative processes. Electroencephalography and functional magnetic resonance imaging studies reflect changes in neural connectivity and network dynamics, and molecular imaging provides molecular-level evidence of these changes.

Conclusion: VCI is caused by the complex interaction of vascular dysfunction, synaptic dysregulation, and epigenetic modification. Identification of these convergent mechanisms may pave the way for new diagnostic biomarkers and therapeutic targets. Future studies on neuroimaging, molecular profiling, and epigenetic modifications could facilitate the early detection and precision-based treatment of VCI and VaD.

Introduction: Obstructive sleep apnea syndrome (OSAS) is positively associated with increased risks of ischemic stroke. Patients with stroke exhibit remarkable gut microbiota dysbiosis. However, the impact of OSAS on gut microbiota of patients with symptomatic intracranial atherosclerotic stenosis (sICAS), one of the most common causes of stroke, remains unknown.

Methods: This study included patients with sICAS, the severity of OSAS was defined by the apnea-hypopnea index (AHI). AHI < 5 was considered no sleep apnea, AHI 5-15 was defined as mild OSAS, AHI 15-30 as moderate OSAS, and AHI > 30 as severe OSAS. Fecal samples were collected and subjected to 16 s rRNA gene sequencing. PICRUSt2 was used to predict the functional properties of the bacterial communities.

Results: In total, 99 sICAS patients were included, with No-OSAS (N = 22), Mild (N = 25), Moderate (N = 30), and Severe (N = 22). Patients with OSAS exhibited significantly altered gut microbiota composition compared to those without sleep apnea, characterized by increased abundances of pathogens such as Escherichia-Shigella and decreased abundances of beneficial microbes such as short-chain fatty acids-producing bacteria Blautia. Importantly, these microbes were significantly associated with AHI. Several microbial metabolic pathways such as Peptidoglycan biosynthesis, C5-branched dibasic acid metabolism, and Pantothenate and CoA biosynthesis were downregulated with OSAS.

Conclusion: OSAS is associated with gut dysbiosis and altered microbial metabolic functions in patients with sICAS.

Objectives: This study aimed to investigate differences in brain imaging characteristics among patients with Parkinson's disease with cognitive impairment (PDCI), Parkinson's disease without cognitive impairment (PDNCI), and healthy controls (HC), and to develop machine learning-based models for the early diagnosis of PDCI. A total of 48 patients with PDCI, 50 patients with PDNCI, and 47 age- and sex-matched healthy controls were enrolled, all of whom underwent magnetic resonance imaging using a 3.0 T MRI scanner. Arterial spin labeling (ASL) was applied to quantify cerebral blood flow (CBF), and quantitative susceptibility mapping (QSM) was used to assess magnetic susceptibility, while cognitive function was evaluated using standardized neuropsychological scales. Group differences were examined using one-way analysis of variance (ANOVA), and seven machine learning classifiers, including random forest (RF), K-nearest neighbors (KNN), and Extreme Gradient Boosting (XGB), were constructed to discriminate among the PDCI, PDNCI, and HC groups. The ANOVA results revealed significant differences in both CBF and magnetic susceptibility between the HC group and the two PD groups, whereas no significant differences were observed between the PDCI and PDNCI groups. Compared with normative data, patients with PDCI exhibited cognitive impairments exceeding 2 standard deviations in the domains of language, attention, and working memory, as well as impairments exceeding 1 standard deviation in visuospatial function, memory, and executive function. Among the machine learning models, RF, KNN, and XGB achieved perfect classification performance, with all evaluation metrics reaching 1.000, indicating excellent discriminative capability. Feature importance analysis identified increased CBF and magnetic susceptibility in regions such as the left precuneus (Precuneus_L) and left postcentral gyrus (Postcentral_L) as key imaging features distinguishing PDCI, and correlation analyses further demonstrated significant associations between cognitive deficits and alterations in CBF and magnetic susceptibility. These findings suggest that ASL- and QSM-derived imaging features have substantial potential as non-invasive biomarkers for the early diagnosis of PDCI, that patients with PDCI exhibit widespread impairments across multiple cognitive domains-particularly in language, attention, and working memory-and that machine learning models integrating multimodal imaging features provide a reliable and effective approach for early diagnosis and may facilitate personalized treatment strategies in Parkinson's disease, although future studies with larger sample sizes and independent validation cohorts are warranted to enhance the robustness and generalizability of these models.

Objective: To explore the effects of oxytocin administration on social cognition and social engagement in patients with behavioral variant frontotemporal dementia.

Methods: In a within-subject, double-blind, placebo-controlled, randomized crossover trial, patients with behavioral variant frontotemporal dementia completed the primary outcome measures, facial emotion and intention recognition tasks. Secondary outcomes included evaluation of drug safety and tolerability and changes in social engagement, assessed through caregiver ratings of social behavior. Exploratory outcomes included anger-bias in emotion misclassification and a LIWC-based analysis of speech during a semi-structured interview.

Results: Oxytocin was safe, well-tolerated, and improved social engagement in naturalistic contexts: caregivers reported positive changes, including increases in awareness, spontaneous initiative, socio-affective engagement, and reductions in appetite/impulsivity. Exploratory analyses suggested that oxytocin reduced the tendency to misclassify fearful and sad expressions as angry and reduced the use of first-person pronouns during spontaneous speech. However, the study detected no improvements in the emotion recognition and observed decreased accuracy in recognizing harmful intentions.

Conclusion: Exploratory findings suggest that oxytocin reduces threat-bias, promotes social engagement, and decreases self-focused language, while no improvements were detected on experimental measures of social cognition. The results highlight the safety and potential of innovative oxytocin-based pharmacological interventions and the value of incorporating naturalistic assessments, such as ecological social interactions and language analysis, to optimize the detection of therapeutic effects in neurodegenerative diseases. Oxytocin may hold promise for enhancing social engagement in behavioral variant frontotemporal dementia, although its effects on language use and higher-order cognitive processes require further investigation.

Background: Cognitive dysfunction affects over 50 million individuals worldwide, with Alzheimer's disease (AD) representing two-thirds of cases. We identified CTHRC1 (Collagen Triple Helix Repeat Containing 1) as a novel candidate associated with cognitive function and neurodegeneration.

Methods: Human proteomic analysis revealed CTHRC1 as highly upregulated in AD patients (~5-fold increase, adj. p = 0.05), with corresponding elevation in 5xFAD mice. Single-cell RNA sequencing showed predominant astrocyte and oligodendrocyte progenitor expression. Using BXD mice, systems genetics analysis revealed associations between hippocampal CTHRC1 expression and 22 cognition-related phenotypes. PheWAS, ePheWAS, and GWAS analyses confirmed links to nervous system and AD-related traits.

Results: eQTL mapping identified CTHRC1 as cis-regulated in hippocampus, and correlating with protein transport, transcription, and neurodegeneration pathways. Network analysis revealed 17 direct interactors, including key neurodegeneration genes (BACE1, NEFL, IRS1, VDAC1, SNCAIP) connecting CTHRC1 to core AD pathways (APP, MAPT, APOE, PSEN1/2). CTHRC1 overexpression in SH-SY5Y cells promoted tau degradation and modulated network partner expression.

Conclusion: CTHRC1 represents a central hub in cognitive function networks, suggesting therapeutic potential for neurodegenerative disorders.

Background: Solitary drinking is a pattern of hazardous alcohol consumption that is problematic at any age but is more prevalent in older adults, yet most research focuses on younger samples. Research on solitary drinking and cognition is critical as older adults are more vulnerable to cognitive decline, and cognitive decline is increased by hazardous drinking.

Methods: Using data from a larger project, the present study explored relationships between cognitive function and solitary drinking among 342 individuals 60 + years old (55.56% Female, 89.47% White). Solitary drinking, objective cognition via the Rey Auditory Verbal Learning Test (Rey), and subjective cognition via the Functional Assessment of Cancer Therapy-Cognitive Function (FactCog) questionnaire were assessed at baseline. The FactCog was also completed at a 4-month assessment.

Results: More frequent solitary drinking was correlated with poorer Rey scores and worse scores on the FactCog subscales Perceived Cognitive Abilities (PCA) and Perceived Cognitive Impairment (PCI; ps < 0.05) among older adults who drank alcohol. Older adults who drank alcohol only in social situations had significantly higher baseline Rey learning scores compared to those who did not drink (p = 0.04) and higher delayed Recall scores compared to those who drink while alone (p = 0.03). They also had significantly higher baseline PCI scores compared to the combined pool of solitary and non-drinking individuals (p = 0.046). Finally, PCI averaged across baseline and 4 months was better among the social-only versus solitary drinking group (p = 0.03).

Conclusion: Our results expand knowledge of solitary drinking in older adulthood by connecting it to poorer objective and subjective cognitive function.