Effects of a Cocktail Supplement of Ginkgo Biloba and Acai Extract on Cognitive Symptoms of Parkinson’s Disease

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive impairment. Current treatments often involve synthetic drugs with significant side effects and potential for dependency. This study investigates the effects of a natural supplement combination of Ginkgo Biloba and Acai Extract on cognitive symptoms in a 77-year-old male with PD. The participant underwent a three-month supplementation regimen, with cognitive function assessed using the Montreal Cognitive Assessment (MoCA) test before and after the intervention. The results indicated an improvement in cognitive scores, suggesting that the combination of Ginkgo Biloba and Acai Extract may offer a promising alternative or adjunct to conventional PD treatments. This study highlights the potential of natural supplements in managing PD symptoms and calls for further research with larger sample sizes to confirm these findings. Human data was performed in accordance with the Declaration of Helsinki by the Roxbury District IRB Board (IRB Number: IRB00011767).

Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty,characterized by the coexistence of cognitive impairment and physical frailty,represents a multifaceted challenge in the aging population.The role of cardiovascular risk factors in this complex interplay is not yet fully understood.AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia.METHODS A comprehensive approach was employed,with a total of 512 communitydwelling older persons aged 60 years and above,involving two cohorts of older persons from previous studies.Datasets related to cardiovascular risks,namely sociodemographic factors,and cardiovascular risk factors,including hypertension,diabetes,hypercholesterolemia,anthropometric characteristics and biochemical profiles,were pooled for analysis.Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score.Cardiovascular risk was determined using Framingham risk score.Statistical analyses were conducted using SPSS version 21.RESULTS Of the study participants,46.3%exhibited cognitive frailty.Cardiovascular risk factors including hypertension(OR:1.60;95%CI:1.12-2.30),low fat-free mass(OR:0.96;95%CI:0.94-0.98),high percentage body fat(OR:1.04;95%CI:1.02-1.06),high waist circumference(OR:1.02;95%CI:1.01-1.04),high fasting blood glucose(OR:1.64;95%CI:1.11-2.43),high Framingham risk score(OR:1.65;95%CI:1.17-2.31),together with sociodemographic factors,i.e.,being single(OR 3.38;95%CI:2.26-5.05)and low household income(OR 2.18;95%CI:1.44-3.30)were found to be associated with cognitive frailty.CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty,a prodromal stage of dementia.Early identification and management of cardiovascular risk factors,particularly among specific group of the population might mitigate the risk of cognitive frailty,hence preventing dementia.

Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia

BACKGROUND Patients with schizophrenia may have various disease manifestations,most of which gradually tend toward incurable chronic decline,leading to mental disability.The basic symptoms of the disease can impair social function,whereas long-term hospitalization produces hospitalization syndrome,causing serious damage to social function.AIM To investigate the effects of Computerized Cognitive Remediation Therapy(CCRT)on cognitive and social functioning in patients with chronic schizophrenia.METHODS A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed.They were divided into an intervention group(60 cases treated with CCRT combined with conventional medication)and a control group(60 cases treated with conventional medication).After treatment,effects on cognitive function and social roles were observed in both groups.The Positive and Negative Syndrome Scale(PANSS)was used to assess the patients'psychiatric symptoms.The Wisconsin Card Sorting Test(WCST)was used to assess the patients'cognitive functioning,and the Social Functioning Scale for Psychiatric Inpatients(SSPI)was used to assess the social functioning of the inpatient psychiatric patients.RESULTS No significant differences were observed in the PANSS,WCST,and SSPI intergroup scores before treatment(P>0.05).After 2,4,and 6 wk of therapy,general psychopathological factors,positive symptoms,negative symptoms,and total PANSS scores of PANSS in the intervention group were lower than in the control group(P<0.05).After 2,4,and 6 wk of treatment,the number of false responses,number of persistent bugs,and total responses in the WCST were significantly lower in the intervention group than in the control group(P<0.05),and the amount of completed classification was significantly higher than in the control group(P<0.05).After 2,4,and 6 wk of therapy,the SSPI scores were significantly greater than those of the controls(P<0.05).After 6 wk of treatment,the efficacy rates of the control and intervention groups were 81.67%and 91.67%,respectively.The curative effect in the intervention group was significantly higher than that in the control group(P<0.05).CONCLUSION CCRT can significantly improve cognitive function and social abilities in patients with chronic schizophrenia.

Exploring the Association between Oral Microbiome and Mild Cognitive Impairment: A Narrative Review

Objective: Some studies have investigated the association between oral microbiome and mild cognitive impairment (MCI). However, there needs to be more narrative reviews synthesizing this evidence. This study aimed to bridge this gap in the current knowledge. Methods: A comprehensive search was conducted on PubMed (MEDLINE) to identify studies examining the association between the oral microbiome and MCI. Search parameters and inclusion criteria were clearly defined, encompassing terms related to the oral microbiome, MCI, and their association. Two authors independently selected relevant studies and performed data extraction. Result: Four studies were included. Two cohort studies and two case-control reported an association between the oral microbiome and MCI. Conclusion: Based on the evidence synthesized from the included studies, the review suggests an association between MCI and the oral microbiome. Specifically, all included studies identified significant differences in the abundance of specific microbial species between individuals with MCI and those with normal cognitive function, underscoring the potential role of these species in neuroinflammatory diseases.

Risk factors for cognitive impairment in patients with chronic kidney disease

BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.

The role of anesthesia in peri-operative neurocognitive disorders:Molecular mechanisms and preventive strategies

Peri-operative neurocognitive disorders(PNDs)include postoperative delirium(POD)and postoperative cognitive dysfunction(POCD).Children and the elderly are the two populations most vulnerable to the development of POD and POCD,which results in both high morbidity and mortality.There are many factors,including neuroinflammation and oxidative stress,that are associated with POD and POCD.General anesthesia is a major risk factor of PNDs.However,the molecular mechanisms of PNDs are poorly understood.Dexmedetomidine(DEX)is a useful sedative agent with analgesic properties,which significantly improves POCD in elderly patients.In this review,the current understanding of anesthesia in PNDs and the protective effects of DEX are summarized,and the underlying mechanisms are further discussed.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Contribution of Metabolic Imaging in the Exploration of Cognitive Disorders Related to COVID-19

On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.

Trends in the Application of Dyadic Coping in Older Adults with Mild Cognitive Impairment and Their Spouses

Dyadic coping plays an important role in older adults with mild cognitive impairment and their spouses. Significant correlations were found between dyadic coping and self-efficacy, anxiety and depression, marital quality, and quality of life in elderly patients with mild cognitive impairment and their spouses, and there were gender differences, with a 36.1% [P = 0.028, OR = 0.639, 95% CI (0.429, 0.952)] and 54% [P = 0.004, OR = 0.460, 95% CI (0.269, 0.785)] reduction in the risk of MCI and dementia for older men aged 65 - 69 years with a spouse and for those aged 80 years and older with a spouse, respectively. In contrast, there was no significant difference in the association between having or not having a spouse and developing MCI and dementia in older women (all P > 0.05). Psychosocial interventions, skills interventions, and exercise from the perspective of dyadic relationships were effective in improving the physical and mental health of older adults with mild cognitive impairment and their spouses. However, there is a lack of specific intervention programs for dyadic relationships in the local cultural context as an entry point. Therefore, it is necessary to draw on internal and external relevant literature to treat both partners as a whole for intervention, provide personalized social, cognitive and motor therapy for patients and promote the integration and participation of caregivers, help patients and spouses to improve the sense of well-being and intimacy, reduce the burden of caregivers, and build a dyadic coping intervention program suitable for elderly patients with mild cognitive impairment in China. The current article aims to provide a conceptual review focusing on dyadic coping care to inform the development of a dyadic intervention program suitable for older adults with mild cognitive impairment in China. This review outlines the theoretical concepts, assessment tools, current state of research, and intervention methods for mild cognitive impairment and dyadic coping.

J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy,older Chinese individuals

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

Measuring Cognitive and Psychosocial Accessibility to Modern Contraception: A Comprehensive Framework

Nowadays, more than ever, the improvement of access to family planning (FP) has become an international goal. What constitutes access to FP? Current human rights-based contraceptive guidelines indicate that access begins as soon as women or couples express a desire to avoid pregnancy and their risk of unintended pregnancy is established. However, few studies have sought to define and measure cognitive and psychosocial access to contraception. To propose a comprehensive framework for the cognitive and psychosocial accessibility of contraception, we critically analyzed the literature on attitudes toward FP. The main dimensions that emerged were knowledge about FP, fear of side effects, approval of contraception, and contraceptive agency. We then identified and adjusted some questions that can capture these dimensions more comprehensively. As a result, we developed a questionnaire module comprising 15 questions, which was integrated into the 6th round of the PMA2020 survey in Burkina Faso in 2019. This research highlighted that previous studies have collected separate dimensions of contraceptive access, and the psychosocial dimension tended to be neglected. Our results demonstrate that it is possible to collect comprehensive data on cognitive and psychosocial dimensions of access to family planning.

The Experience and Impact of a Fitbit-Based Physical Activity and Sleep Hygiene Intervention for Older Adults Experiencing Cognitive Decline

Objectives: This study aimed to understand the experience and impact of a physical activity and sleep wrist-worn tracker (Fitbit)-based healthy lifestyle intervention for older patients attending a memory assessment service, who are experiencing cognitive impairment but do not receive a dementia diagnosis. Methods: A qualitative design was employed. Semi-structured interviews were conducted with a purposeful sample of thirteen participants recruited from a memory assessment service. Thematic analysis, that was data driven and inductive, was undertaken to analyse the data. Results: Two global themes were developed. “Understanding exercise and sleep as part of my lifestyle” was made up of themes representing how participants viewed exercise and sleep as part of their lifestyles in terms of acknowledging the positive impacts and the barriers to exercise and sleep. The second global theme “Understanding my experience of the healthy lifestyle intervention” was made up of themes that identified the positive impact of the intervention regarding improving health and wellbeing, enabling validation of proactive behaviours and motivation to engage in healthy lifestyle behaviours, so promoting positive behaviour change. Conclusion: Patients experiencing age-related cognitive impairment, applied and benefited from a healthy lifestyle Fitbit-based intervention to facilitate and promote physical activity, better sleep hygiene and healthy lifestyles.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.