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Journal of Integrative Neuroscience Sep 2023Patients with post-stroke memory disorder (PSMD) have poor quality of life and it is necessary to identify more beneficial stimulation protocols for treatment with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with post-stroke memory disorder (PSMD) have poor quality of life and it is necessary to identify more beneficial stimulation protocols for treatment with repetitive transcranial magnetic stimulation (rTMS). This meta-analysis was conducted to investigate the efficacy and safety of rTMS for improving memory performance, global cognition, and activities of daily living (ADL) among patients with PSMD.
METHODS
The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang databases were screened to identify relevant randomized controlled trials. The primary outcome was memory performance; secondary outcomes included global cognition, ADL, and adverse events. STATA software was used to perform data synthesis.
RESULTS
Five articles with a total of 192 participants were included. The results indicated that rTMS was superior to control treatments for improving memory performance (mean difference [MD] = 1.73, 95% CI [Confidence Interval] [0.85, 2.60], 0.001), global cognition (MD = 2.44, 95% CI [0.96, 3.93], 0.001), and ADL (MD = 10.29, 95% CI [5.10, 15.48], 0.001). No significant differences were found between the low-frequency (LF) and high-frequency (HF) rTMS subgroups ( 0.47, = 0.00%) or between the sham rTMS and non-rTMS subgroups ( 0.94, = 0.00%). Four studies did not reported adverse events.
CONCLUSIONS
rTMS may improve memory function, global cognition, and the ability to perform ADL in patients with PSMD. LF-rTMS and HF-rTMS may have equal efficacy for treatment of PSMD. Future studies should consider extending the follow-up period to explore the safety and long-term efficacy of rTMS for treatment of PSMD and the appropriate choice of placebo for clinical trials of this treatment.
Topics: Humans; Transcranial Magnetic Stimulation; Activities of Daily Living; Quality of Life; Memory Disorders; Memory; Stroke
PubMed: 37735134
DOI: 10.31083/j.jin2205131 -
Translational Psychiatry Feb 2024Memory persistence is a double edge sword. Persistence of adaptive memories is essential for survival and even determines who we are. Neurodegenerative conditions with... (Review)
Review
Memory persistence is a double edge sword. Persistence of adaptive memories is essential for survival and even determines who we are. Neurodegenerative conditions with significant memory loss such as Alzheimer's disease, testify how defects of memory persistence have severe and irreversible effects on personality, among other symptoms. Yet, maintenance of overly strong maladaptive memories underlies highly debilitating psychiatric conditions including post-traumatic stress disorder, specific phobia, substance dependence and binge eating disorder. Here we review the neurobiological mechanisms supporting memory formation, persistence, inhibition and forgetting. We then shift the focus to how such mechanisms have been exploited to alter the persistence of laboratory-generated memories in human healthy volunteers as a proof of concept. Finally, we review the effect of behavioural and pharmacological interventions in anxiety and addiction disorder patients, highlighting key findings, gaps, and future directions for basic and translational research.
Topics: Humans; Anxiety Disorders; Stress Disorders, Post-Traumatic; Phobic Disorders; Substance-Related Disorders; Memory Disorders
PubMed: 38355584
DOI: 10.1038/s41398-024-02808-z -
Translational Psychiatry Apr 2023Carboxypeptidase E (CPE) is a multifunctional protein with many nonenzymatic functions in various systems. Previous studies using CPE knock-out mice have shown that CPE...
Carboxypeptidase E (CPE) is a multifunctional protein with many nonenzymatic functions in various systems. Previous studies using CPE knock-out mice have shown that CPE has neuroprotective effects against stress and is involved in learning and memory. However, the functions of CPE in neurons are still largely unknown. Here we used a Camk2a-Cre system to conditionally knockout CPE in neurons. The wild-type, CPE, and CPE mice were weaned, ear-tagged, and tail clipped for genotyping at 3 weeks old, and they underwent open field, object recognition, Y-maze, and fear conditioning tests at 8 weeks old. The CPE mice had normal body weight and glucose metabolism. The behavioral tests showed that CPE mice had impaired learning and memory compared with wild-type and CPE mice. Surprisingly, the subiculum (Sub) region of CPE mice was completely degenerated, unlike the CPE full knockout mice, which exhibit CA3 region neurodegeneration. In addition, doublecortin immunostaining suggested that neurogenesis in the dentate gyrus of the hippocampus was significantly reduced in CPE mice. Interestingly, TrkB phosphorylation in the hippocampus was downregulated in CPE mice, but brain-derived neurotrophic factor levels were not. In both the hippocampus and dorsal medial prefrontal cortex, we observed reduced MAP2 and GFAP expression in CPE mice. Taken together, the results of this study demonstrate that specific neuronal CPE knockout leads to central nervous system dysfunction in mice, including learning and memory deficits, hippocampal Sub degeneration and impaired neurogenesis.
Topics: Mice; Animals; Mice, Knockout; Carboxypeptidase H; Hippocampus; Learning; Memory Disorders; Maze Learning
PubMed: 37100779
DOI: 10.1038/s41398-023-02429-y -
Translational Psychiatry Dec 2023Current evidence-based treatments for post-traumatic stress disorder (PTSD) are efficacious in only part of PTSD patients. Therefore, novel neurobiologically informed... (Meta-Analysis)
Meta-Analysis
Current evidence-based treatments for post-traumatic stress disorder (PTSD) are efficacious in only part of PTSD patients. Therefore, novel neurobiologically informed approaches are urgently needed. Clinical and translational neuroscience point to altered learning and memory processes as key in (models of) PTSD psychopathology. We extended this notion by clarifying at a meta-level (i) the role of information valence, i.e. neutral versus emotional/fearful, and (ii) comparability, as far as applicable, between clinical and preclinical phenotypes. We hypothesized that cross-species, neutral versus emotional/fearful information processing is, respectively, impaired and enhanced in PTSD. This preregistered meta-analysis involved a literature search on PTSD+Learning/Memory+Behavior, performed in PubMed. First, the effect of information valence was estimated with a random-effects meta-regression. The sources of variation were explored with a random forest-based analysis. The analyses included 92 clinical (N = 6732 humans) and 182 preclinical (N = 6834 animals) studies. A general impairment of learning, memory and extinction processes was observed in PTSD patients, regardless of information valence. Impaired neutral learning/memory and fear extinction were also present in animal models of PTSD. Yet, PTSD models enhanced fear/trauma memory in preclinical studies and PTSD impaired emotional memory in patients. Clinical data on fear/trauma memory was limited. Mnemonic phase and valence explained most variation in rodents but not humans. Impaired neutral learning/memory and fear extinction show stable cross-species PTSD phenotypes. These could be targeted for novel PTSD treatments, using information gained from neurobiological animal studies. We argue that apparent cross-species discrepancies in emotional/fearful memory deserve further in-depth study; until then, animal models targeting this phenotype should be applied with utmost care.
Topics: Animals; Humans; Stress Disorders, Post-Traumatic; Fear; Extinction, Psychological; Learning; Memory; Memory Disorders
PubMed: 38062029
DOI: 10.1038/s41398-023-02660-7 -
Annals of Clinical and Translational... Jun 2021Sleep-dependent memory processing occurs in animals including humans, and disturbed sleep negatively affects memory. Sleep disturbance and memory dysfunction are common...
OBJECTIVE
Sleep-dependent memory processing occurs in animals including humans, and disturbed sleep negatively affects memory. Sleep disturbance and memory dysfunction are common in multiple sclerosis (MS), but little is known about the contributions of sleep disturbance to memory in MS. We investigated whether subjective sleep disturbance is linked to worse memory in early MS independently of potential confounders.
METHODS
Persons with early MS (n = 185; ≤5.0 years diagnosed) and demographically matched healthy controls (n = 50) completed four memory tests to derive a memory composite, and four speeded tests to derive a cognitive efficiency composite. Z-scores were calculated relative to healthy controls. Sleep disturbance was defined by the Insomnia Severity Index score ≥ 10. ANCOVAs examined differences in memory and cognitive efficiency between patients with and without sleep disturbance controlling for potential confounds (e.g., mood, fatigue, disability, T2 lesion volume, gray matter volume). Comparisons were made to healthy controls.
RESULTS
Seventy-four (40%) patients reported sleep disturbance. Controlling for all covariates, patients with sleep disturbance had worse memory (z = -0.617; 95% CI: -0.886, -0.348) than patients without disturbance (z = -0.171, -0.425, 0.082, P = .003). Cognitive efficiency did not differ between groups. Relative to healthy controls, memory was worse among patients with sleep disturbance, but not among patients without sleep disturbance.
INTERPRETATION
Sleep disturbance contributes to MS memory dysfunction, which may help explain differential risk for memory dysfunction in persons with MS, especially since sleep disturbance is common in MS. Potential mechanisms linking sleep disturbance and memory are discussed, as well as recommendations for further mechanistic and interventional research.
Topics: Adult; Cognitive Dysfunction; Female; Humans; Male; Memory Disorders; Multiple Sclerosis; Sleep Wake Disorders
PubMed: 33951348
DOI: 10.1002/acn3.51262 -
Brain Connectivity Sep 2020The fornix is the primary axonal tract of the hippocampus, connecting it to modulatory subcortical structures. This review reveals that fornix damage causes cognitive... (Review)
Review
The fornix is the primary axonal tract of the hippocampus, connecting it to modulatory subcortical structures. This review reveals that fornix damage causes cognitive deficits that closely mirror those resulting from hippocampal lesions. We reviewed the literature on the fornix, spanning non-human animal lesion research, clinical case studies of human patients with fornix damage, as well as diffusion-weighted imaging (DWI) work that evaluates fornix microstructure in vivo. The fornix is essential for memory formation because it serves as the conduit for theta rhythms and acetylcholine, as well as providing mnemonic representations to deep brain structures that guide motivated behavior, such as when and where to eat. In rodents and non-human primates, fornix lesions lead to deficits in conditioning, reversal learning, and navigation. In humans, damage to the fornix manifests as anterograde amnesia. DWI research reveals that the fornix plays a key role in mild cognitive impairment and Alzheimer's Disease, and can potentially predict conversion from the former to the latter. Emerging DWI findings link perturbations in this structure to schizophrenia, mood disorders, and eating disorders. Cutting-edge research has investigated how deep brain stimulation of the fornix can potentially attenuate memory loss, control epileptic seizures, and even improve mood. The fornix is essential to a fully functioning memory system and is implicated in nearly all neurological functions that rely on the hippocampus. Future research needs to use optimized DWI methods to study the fornix in vivo, which we discuss, given the difficult nature of fornix reconstruction. Impact Statement The fornix is a white matter tract that connects the hippocampus to several subcortical brain regions and is pivotal for episodic memory functioning. Functionally, the fornix transmits essential neurotransmitters, as well as theta rhythms, to the hippocampus. In addition, it is the conduit by which memories guide decisions. The fornix is biomedically important because lesions to this tract result in irreversible anterograde amnesia. Research using in vivo imaging methods has linked fornix pathology to cognitive aging, mild cognitive impairment, psychosis, epilepsy, and, importantly, Alzheimer's Disease.
Topics: Animals; Diffusion Magnetic Resonance Imaging; Female; Fornix, Brain; Memory Disorders; Memory, Episodic; Mental Disorders; Neural Pathways
PubMed: 32567331
DOI: 10.1089/brain.2020.0749 -
BMC Geriatrics Oct 2019Subjective memory complaint (SMCs) is a common trait amongst older population. The subjective cognition about their memory could depend on objective cognition. The aim...
BACKGROUND
Subjective memory complaint (SMCs) is a common trait amongst older population. The subjective cognition about their memory could depend on objective cognition. The aim of the current study was to examine the interaction between subjective memory cognition (i.e., SMC) and objective cognition on cognitive functions in participants from older generation.
METHODS
A total of 219 patients, 181 normal control (NC) patients and 38 patients with mild cognitive impairment (MCI), were examined through standardized and comprehensive clinical evaluation and neuropsychological assessment. The Subjective Memory Complaints Questionnaire was used to assess SMCs along with five cognitive tasks were used to evaluate cognitive decline over following areas: verbal memory, visuospatial memory, attention, fluency, and language.
RESULTS
The results of 2 × 2 two-way analysis of variance (ANOVA) showed that there were significant interactions between SMCs and cognitive status (NC, MCI) on memory performances. NC with SMCs showed significantly lower performance in verbal memory and visuospatial memory compared to NCs without SMCs. Conversely, no effect was observed in the MCI group.
CONCLUSION
There are interactions between subjective cognition (i.e., SMC) and objective cognition (i.e., cognitive status) on memory performances in older adults. The roles of SMCs on memory performances should be interpreted with older adults' objective cognitive status.
Topics: Aged; Aging; Cognition; Cognitive Dysfunction; Correlation of Data; Diagnostic Self Evaluation; Female; Humans; Male; Memory; Memory Disorders; Neuropsychological Tests; Surveys and Questionnaires
PubMed: 31666029
DOI: 10.1186/s12877-019-1322-9 -
Neurology Oct 2023The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use of memory clinics, this could exacerbate health care disparities, especially if more effective treatments of Alzheimer disease become available. We aimed to understand how use of a memory clinic is associated with neighborhood-level measures of socioeconomic factors and the intersectionality of race.
METHODS
We conducted an observational cross-sectional study using electronic health record data to compare the neighborhood advantage of patients seen at the Washington University Memory Diagnostic Center with the catchment area using a geographical information system. Furthermore, we compared the severity of dementia at the initial visit between patients who self-identified as Black or White. We used a multinomial logistic regression model to assess the Clinical Dementia Rating at the initial visit and tests to compare neighborhood characteristics, including Area Deprivation Index, with those of the catchment area.
RESULTS
A total of 4,824 patients seen at the memory clinic between 2008 and 2018 were included in this study (mean age 72.7 [SD 11.0] years, 2,712 [56%] female, 543 [11%] Black). Most of the memory clinic patients lived in more advantaged neighborhoods within the overall catchment area. The percentage of patients self-identifying as Black (11%) was lower than the average percentage of Black individuals by census tract in the catchment area (16%) ( < 0.001). Black patients lived in less advantaged neighborhoods, and Black patients were more likely than White patients to have moderate or severe dementia at their initial visit (odds ratio 1.59, 95% CI 1.11-2.25).
DISCUSSION
This study demonstrates that patients living in less affluent neighborhoods were less likely to be seen in one large memory clinic. Black patients were under-represented in the clinic, and Black patients had more severe dementia at their initial visit. These findings suggest that patients with a lower socioeconomic status and who identify as Black are less likely to be seen in memory clinics, which are likely to be a major point of access for any new Alzheimer disease treatments that may become available.
Topics: Aged; Female; Humans; Male; Alzheimer Disease; Black People; Cross-Sectional Studies; Racial Groups; Socioeconomic Factors; United States; Memory Disorders; White People; Neighborhood Characteristics; Middle Aged; Aged, 80 and over
PubMed: 37532510
DOI: 10.1212/WNL.0000000000207674 -
Archives of Clinical Neuropsychology :... Aug 2022The etiology of persistent memory complaints after concussion is poorly understood. Memory perfectionism (highly valuing memory ability and intolerance of minor memory... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The etiology of persistent memory complaints after concussion is poorly understood. Memory perfectionism (highly valuing memory ability and intolerance of minor memory lapses) may help explain why some people report persistent subjective memory problems in the absence of corresponding objective memory impairment. This study investigated the relationship between memory perfectionism and persistent memory complaints after concussion.
METHODS
Secondary analysis of baseline data from a randomized controlled trial. Adults (N = 77; 61% women) with persistent symptoms following concussion were recruited from outpatient specialty clinics. Participants completed the National Institutes of Health Toolbox Cognition Battery, Test of Memory Malingering-Trial 1, and questionnaires measuring memory perfectionism (Metamemory in Adulthood-Achievement subscale), forgetfulness and other postconcussion symptoms (Rivermead Postconcussion Symptoms Questionnaire; RPQ), and depression (Patient Health Questionnaire-2) at M = 17.8 weeks postinjury. Patients with versus without severe memory complaints (based on the RPQ) were compared.
RESULTS
Memory perfectionism was associated cross-sectionally with severe memory complaint, after controlling for objective memory ability, overall cognitive ability, and depression (95% confidence interval for odds ratio = 1.11-1.40). Sensitivity analyses showed that this relationship did not depend on use of specific objective memory tests nor on inclusion of participants who failed performance validity testing. In a control comparison to test the specificity of identified relationships, memory perfectionism was not associated with severe fatigue (95% confidence interval for odds ratio = 0.91-1.07).
CONCLUSIONS
Memory perfectionism may be a risk factor for persistent memory symptoms after concussion, with potential relevance to the spectrum of functional cognitive disorders more broadly.
Topics: Adult; Brain Concussion; Cognition; Cognition Disorders; Female; Humans; Male; Memory Disorders; Neuropsychological Tests; Post-Concussion Syndrome
PubMed: 35443277
DOI: 10.1093/arclin/acac021 -
Nutrients May 2023Memory impairment is a characteristic of brain aging, and it is associated with a decrease in neurogenesis. Therefore, enhancing neurogenesis is a potential method for...
Memory impairment is a characteristic of brain aging, and it is associated with a decrease in neurogenesis. Therefore, enhancing neurogenesis is a potential method for mitigating brain aging. Nobiletin (NOB) is a natural polymethoxylated flavonoid derived from citrus peels. It acts as an antioxidant, enhances anti-inflammation, and displays neuroprotective properties. However, the mechanism of NOB on brain aging has not been elucidated. In this study, D-galactose-induced aging mice were treated with NOB (100 mg/kg/day) for 10 weeks. NOB administration attenuated D-galactose-induced memory impairment and restored hippocampal neurogenesis, including the number of newborn neurons and neural stem cells in mice. Furthermore, it downregulated the pro-inflammatory mediators IL-1 β, IL-6, and pP65 (by 42.2%, 22.9%, and 46.4% of those in the D-galactose treated group, respectively) in the hippocampus and blocked microglia and astrocyte activation. In vitro, NOB inhibited D-galactose-induced inflammatory responses in BV2 cells, and the conditioned medium prepared from NOB- and D-galactose-co-treated BV2 cells elevated the viability (90.3% of control) and differential ability (94.9% of control) of C17.2 cells, compared to the D-galactose-treated group alone. It was concluded that NOB could restore memory impairment via the improvement of neurogenesis by ameliorating neuroinflammation in the hippocampus. Overall, NOB is a potential candidate neurogenesis enhancer for improving brain function.
Topics: Animals; Mice; Galactose; Flavones; Neurogenesis; Memory Disorders; Hippocampus
PubMed: 37432372
DOI: 10.3390/nu15092228