Beneficial effects of metformin treatment on memory impairment.

Memory issues are a prevalent symptom in different neurodegenerative diseases and can also manifest in certain psychiatric conditions. Despite limited medications approved for treating memory problems, research suggests a lack of sufficient options in the market. Studies indicate that a significant percentage of elderly individuals experience various forms of memory disorders. Metformin, commonly prescribed for type 2 diabetes, has shown neuroprotective properties through diverse mechanisms. This study explores the potential of metformin in addressing memory impairments. The current research gathered its data by conducting an extensive search across electronic databases including PubMed, Web of Science, Scopus, and Google Scholar. Previous research suggests that metformin enhances brain cell survival and memory function in both animal and clinical models by reducing oxidative stress, inflammation, and cell death while increasing beneficial neurotrophic factors. The findings of the research revealed that metformin is an effective medication for enhancing various types of memory problems in numerous studies. Given the rising incidence of memory disorders, it is plausible to utilize metformin, which is an affordable and accessible drug. It is often recommended as a treatment to boost memory.

Cerebellar syndrome as the presenting feature of Hashimoto encephalopathy.

Hashimoto encephalopathy presents with a myriad of neuropsychiatric features in the background of elevated antithyroid antibodies and it may or may not be associated with Hashimoto thyroiditis. It is a diagnosis of exclusion. Here, we present the case of a hypothyroid woman in her 30s, with a 5-year history of chronic progressive gait ataxia along with hand and head tremor, inattention and electroencephalogram (EEG) suggestive of interictal epileptiform discharges without any clinical seizures. The patient had very high titres of anti-thyroid peroxidase antibodies >2000 IU/mL and was on very high-dose levothyroxine replacement therapy. She responded to intravenous pulse corticosteroids. Improvement was noted both clinically and on subsequent EEGs. Pure cerebellar syndrome without frank encephalopathy can also be a rare presentation of Hashimoto encephalopathy. This highlights the importance of antithyroid antibodies testing even in cases of pure cerebellar syndrome to rule out Hashimoto encephalopathy associated ataxia.

Post-COVID-19 cognitive symptoms in patients assisted by a teleassistance service: a retrospective cohort study.

Introduction: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. Objective: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Methods: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. Results: From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). Conclusion: In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.

Dementia Knowledge Among Primary Healthcare Physicians in Riyadh, Saudi Arabia.

INTRODUCTION: Dementia poses a significant healthcare challenge globally, and healthcare providers must have adequate knowledge about its diagnosis, management, and support services. By assessing the knowledge level of primary care physicians in Riyadh, we can identify potential gaps and areas for improvement in dementia care, ultimately enhancing patient outcomes and quality of life. This study holds promise in shedding light on the current state of dementia knowledge among primary healthcare physicians in Riyadh and offering insights into strategies to enhance dementia care in this region. METHODS: This cross-sectional questionnaire-based study was conducted from the first of June 2023 to the end of December 2023 in Riyadh, Saudi Arabia. A validated questionnaire was used to assess physicians' knowledge, attitude, and practice toward dementia. RESULTS: A total of 151 physicians completed the questionnaires. The majority were male (55%), below 30 years of age (88.1%), and family medicine residents (84.8%). Most (74.8%) recognized old age as the most significant risk factor; an overwhelming majority of participants (98.7%) could not identify the minimum course of treatment to judge a medication's effectiveness. The average score of correct responses (7.74 ∓ 4.11) was equivalent to 38.7%. Furthermore, the average correct responses were significantly different among the different job levels of the participants. CONCLUSIONS: The findings of this study highlight a lack of knowledge among primary care physicians regarding dementia, emphasizing the crucial importance of physician education in this area. Additionally, the results strongly indicate the need for emphasis on dementia education within the undergraduate medical curriculum, family medicine curriculum, and physician training programs. By addressing these educational gaps, we can better equip physicians to provide optimal care and support for individuals with dementia, ultimately improving patient care and quality of life.

Long-term cognitive effects of COVID-19 studied with repeated neuropsychological testing.

COVID-19 has a wide range of clinical manifestations. Apart from respiratory symptoms, neurological manifestations and cognitive impairment are commonly seen. Due to lack of a clear consensus on the definition of long COVID a pragmatic approach of assessing change from neurological baseline has become prevalent. We present the case of a high functioning woman in her late 40s who had a mild course of acute illness but developed cognitive difficulties. No organic causes for her cognitive difficulties were found. Neuropsychological testing showed impairment in right frontal lobe functioning. The patient showed a response to empirical treatment with Attention deficit hyperactivity disorder (ADHD) medications. Repeat neuropsychological testing 1 year later showed continued dysfunction in executive functioning. We present the details of her test findings and discuss the proposed pathophysiology behind neurocognitive effects of long COVID.

Advancements in research on the effects of panax notoginseng saponin constituents in ameliorating learning and memory disorders.

Learning and memory disorder is a cluster of symptoms caused by neuronal aging and other diseases of the central nervous system (CNS). Panax notoginseng saponins (PNS) are a series of saponins derived from the natural active ingredients of traditional Chinese medicine (TCM) that have neuroprotective effects on the central nervous system. In this paper, we review the ameliorative effects and mechanisms of Panax notoginseng saponin-like components on learning and memory disorders to provide valuable references and insights for the development of new drugs for the treatment of learning and memory disorders. Our summary results suggest that Panax ginseng saponins have significant effects on improving learning and memory disorders, and these effects and potential mechanisms are mediated by their anti-inflammatory, anti-apoptotic, antioxidant, ß-amyloid lowering, mitochondrial homeostasis in vivo, neuronal structure and function improving, neurogenesis promoting, neurotransmitter release regulating, and probiotic homeostasis in vivo activities. These findings suggest the potential of Panax notoginseng saponin-like constituents as drug candidates for improving learning and memory disorders.

Chronic high-dose dimenhydrinate use contributing to early multifactorial cognitive impairment.

Dimenhydrinate is an over-the-counter antihistaminergic medication with anticholinergic properties used to treat nausea or motion sickness worldwide. There is a well-established correlation between the use of anticholinergic medications and dementia, however, it is unclear if a causal role exists. We report a case of minor neurocognitive disorder in a woman in her 40s with several years of high-dose daily dimenhydrinate abuse who subsequently developed significant delusional beliefs. Her clinical presentation was confounded by numerous other factors that could have impacted her cognition, such as a longstanding presumed learning disability, ankylosing spondylitis with adalimumab treatment, extensive cannabis use or potential development of a primary psychotic disorder. Her workup was within normal limits, and she has not responded to first-line antipsychotic medications to date. This case report adds to the growing evidence supporting concerns about potentially irreversible cognitive deficits in chronic misuse of anticholinergic agents, an association previously observed only in the elderly population.

Variably protease-sensitive prionopathy with methionine homozygosity at codon 129 in the prion protein gene.

Variably protease-sensitive prionopathy (VPSPr) is a recently characterised rare subtype of sporadic prion disease, mainly affecting individuals with valine homozygosity at codon 129 in the prion protein gene, with only seven methionine homozygote cases reported to date. This case presents clinical, neuropathological and biochemical features of the eighth VPSPr case worldwide with methionine homozygosity at codon 129 and compares the features with the formerly presented cases.The patient, a woman in her 70s, presented with cognitive decline, impaired balance and frequent falls. Medical history and clinical presentation were suggestive of a rapidly progressive dementia disorder. MRI showed bilateral thalamic hyperintensity. Cerebrospinal fluid real-time quaking-induced conversion was negative, and the electroencephalogram was unremarkable. The diagnosis was established through post-mortem pathological examinations. VPSPr should be suspected in rapidly progressive dementia lacking typical features or paraclinical results of protein misfolding diseases.

Tooth loss mediates the association between smoking and an increased risk of dementia among older adults: The JAGES prospective cohort study.

AIM: Tooth loss has various causes; however, its cause-specific effects on health outcomes remain unclear. This study evaluated whether the association between past/current smoking and risk of dementia was mediated by tooth loss. MATERIALS AND METHODS: This 9-year-follow-up prospective cohort study targeted adults aged ≥65 years. Dementia incidence during 2013-2019, smoking status (never, past/current) in 2010 and the number of remaining teeth (≤19, ≥20) in 2013 were the outcome, exposure and mediator, respectively. We used causal mediation analysis to fit the Cox proportional hazards model and estimated the hazard ratio (HR) and 95% confidence interval (CI) of the natural indirect effect (NIE) of smoking on dementia incidence through tooth loss and their mediated proportions. RESULTS: Among 32,986 participants (mean age 72.6 years [1 SD = 5.4]; men 48.4%), the dementia incidence during follow-up was 2.11/100 person-years. Tooth loss significantly mediated the association between past/current smoking and dementia incidence; the NIE of fewer remaining teeth for past/current smokers compared to never smokers was HR = 1.03 (95% CI: 1.02-1.05), and the mediated proportion was 18.0%. CONCLUSIONS: Tooth loss significantly mediates the association between past/current smoking and an increased risk of dementia among older adults.

Wernicke encephalopathy: limitations in a laboratory and radiological diagnosis.

Wernicke encephalopathy is an emergent neurological disorder caused by vitamin B1 (thiamine) deficiency. Here, we present a case of Wernicke encephalopathy in a male patient in his 70s with normal serum thiamine levels and MRI findings on admission. He had a history of heavy alcohol consumption and a gradual decrease in food intake. On arrival at the hospital, his consciousness was impaired which persisted even after glucose replacement. Moreover, horizontal nystagmus and cerebellar ataxia were observed. Head CT scan and MRI revealed no abnormal findings. Further, his serum thiamine level was within the normal range. The patient was clinically diagnosed with Wernicke encephalopathy, and high-dose thiamine therapy was started. Then, his symptoms improved immediately. Thus, in case of clinical suspicion, treatment for Wernicke encephalopathy must be initiated promptly even in patients with normal serum thiamine levels.

Over a Century of Study and Still Misunderstood: Recognizing the Spectrum of Acute and Chronic Wernicke-Korsakoff Syndrome.

The aim of this study was to objectively evaluate the hypothesis that the neuropsychological presentation of Korsakoff's syndrome, the chronic phase of Wernicke-Korsakoff syndrome (WKS), is invariably a severe, selective amnesia against a background of relatively preserved general intellectual functions in a consecutive clinical sample. An analysis of the neuropsychological profiles of nine cases with a recorded history of WKS was undertaken. All cases were adult males (ages 32 to 70) with a long history of alcohol use disorder. Eight cases were chosen retrospectively on a consecutive basis from patient referrals. One additional case was recruited prospectively. Conventional understanding and some current opinion of Korsakoff's syndrome predicts anterograde memory to be consistently more impaired than other cognitive abilities, but this was not found in this case series. The Mean Wechsler Delayed Memory Index was not significantly different from the Wechsler Full-Scale IQ (FSIQ), p = 0.130. Regression of Delayed Memory on FSIQ produced a non-significant intercept, p = 0.213. The 'hallmark' criterion of anterograde memory score at least 20 points less than intelligence score was observed in four of eight cases with available data, equating to a 'sensitivity' of 50%. Three of eight cases with available data had an FSIQ less than the memory score. Contrary to a common view, general intellectual function was not consistently preserved in Korsakoff's syndrome relative to memory function. This study illustrates one of the specific merits of case series, namely, to critique an established view. Clinicians and researchers should expand their diagnostic criteria for Korsakoff's syndrome to include more variable cognitive phenotypes, including a potentially reversible dementia-like impairment of variable severity, and focus on potential treatment opportunities.

Intranasal administration of induced pluripotent stem cell-derived cortical neural stem cell-secretome as a treatment option for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, resulting in gradual destruction of cognitive abilities. Research on the development of various AD treatments is underway; however, no definitive treatment has been developed yet. Herein, we present induced pluripotent stem cell (iPSC)-derived cortical neural stem cell secretome (CNSC-SE) as a new treatment candidate for AD and explore its efficacy. METHODS: We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation. Then to confirm the efficacy in vivo, CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity (5 µg/g, once a week, 4 weeks). The cell-mediated effects on nerve recovery, amyloid beta (Aß) plaque aggregation, microglial and astrocyte detection in the brain, and neuroinflammatory responses were investigated. Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects. RESULTS: Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro. Furthermore, CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts. The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aß plaque accumulation. CONCLUSIONS: Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential, non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.

Time Perception and Memory in Mild Cognitive Impairment and Alzheimer's Disease: A Preliminary Study.

Background and Purpose: Episodic memory is a system that receives and stores information about temporally dated episodes and their interrelations. Our study aimed to investigate the relevance of episodic memory to time perception, with a specific focus on simultaneity/order judgment. Methods: Experiment 1 employed the simultaneity judgment task to discern differences in time perception between patients with mild cognitive impairment or dementia, and age-matched normals. A mathematical analysis capable of estimating subjects' time processing was utilized to identify the sensory and decisional components of temporal order and simultaneity judgment. Experiment 2 examined how differences in temporal perception relate to performance in temporal order memory, in which time delays play a critical role. Results: The temporal decision windows for both temporal order and simultaneity judgments exhibited marginal differences between patients with episodic memory impairment, and their healthy counterparts (p = 0.15, t(22) = 1.34). These temporal decision windows may be linked to the temporal separation of events in episodic memory (Pearson's ρ = -0.53, p = 0.05). Conclusions: Based on our findings, the frequency of visual events accumulated and encoded in the working memory system in the patients' and normal group appears to be approximately (5.7 and 11.2) Hz, respectively. According to the internal clock model, a lower frequency of event pulses tends to result in underestimation of event duration, which phenomenon might be linked to the observed time distortions in patients with dementia.

Quality of interaction between the nursing personnel and the informal caregivers of people with memory disorders: A systematic review and metasummary of qualitative studies.

AIM: To explore the factors that affect the quality of interactions between nursing personnel and the informal caregivers of people with memory disorders. DESIGN: Systematic review and metasummary of qualitative empirical research. METHODS: The literature search targeted studies concerning the professional care interactions between nursing personnel and the informal caregivers of people with progressive memory disorders. The search in PubMed, CINAHL, PsycINFO and Scopus covered records from the earliest possible date up to December 2020. The data were summarised using a qualitative metasummary method. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist was used to validate the reporting process. RESULTS: Ten articles were included. As presented in 33 statements, the factors affecting the quality of interactions were related to (1) expectations, (2) memory disorders, (3) interaction strategies, (4) time and place of interactions and (5) organisational aspects. Meeting the individual interactional needs of informal caregivers is recommended. The results provide guidance for improving the quality of interactions between nursing personnel and informal caregivers.

Abnormal clinical presentation and surgical outcome of an intraventricular cavernoma of the third ventricle.

We present a unique case of a man presenting with progressive short-term memory deficits over 10+ years who was found to have a large intraventricular cavernoma in the anterior wall of the third ventricle with invasion of medial limbic structures. Identifying intraventricular cavernomas early is crucial to prevent substantial growth and to increase the chance of successful patient outcomes.

Role of neurorehabilitation in the recovery of bilateral thalamic stroke related to the artery of Percheron anatomical variant.

Bilateral thalamic stroke is a rare condition, mostly related to the presence of the artery of Percheron (AoP) variant. The clinical presentation of AoP-related strokes is remarkably heterogeneous and often includes cognitive and behavioural alterations. Our report describes the clinical course of an AoP-related bilateral thalamic stroke and highlights the pivotal role of a tailored rehabilitation programme plays in enhancing recovery. A man in his 40s was admitted to the neurology ward due to the abrupt onset of mental status alterations and weakness in his left limbs. The first brain CT scan and subsequent MRI exam revealed a bilateral thalamic stroke and the presence of an AoP anatomical variant. After the first critical phase, the patient's condition became stable, but he still suffered from severe attention, memory and speech deficits. The patient was then transferred to the rehabilitation unit and was subjected to a tailored neurorehabilitation programme that allowed a complete recovery of the symptoms. Neurorehabilitation plays a pivotal role in the patient's recovery and should always be pursued to minimise the residual deficits and, most importantly, to prevent permanent cognitive deficits.

Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation for Poststroke Memory Disorder: A Meta-Analysis and Systematic Review.

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], p < 0.001), global cognition (MD = 2.44, 95% CI [0.96, 3.93], p < 0.001), and ADL (MD = 10.29, 95% CI [5.10, 15.48], p < 0.001). No significant differences were found between the low-frequency (LF) and high-frequency (HF) rTMS subgroups (p = 0.47, I2 = 0.00%) or between the sham rTMS and non-rTMS subgroups (p = 0.94, I2 = 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.

Hypothalamic orexins as possible therapeutic agents in threat and spatial memory disorders.

Orexin-A and orexin-B, neuropeptides produced exclusively in the lateral hypothalamus, have been implicated in various functions, including memory. Their levels are elevated in certain pathological states, such as PTSD, and lowered in other states, e.g., memory deficits. Recent developments have shown the possibilities of using orexins to modulate memory. Their administration can improve the results of test animals in paradigms such as passive avoidance (PA), cued fear conditioning (CFC), and the Morris water maze (MWM), with differences between the orexin used and the route of drug administration. Blocking orexin receptors in different brain structures produces opposing effects of memory impairments in given paradigms. Therefore, influencing the orexinergic balance of the brain becomes a viable way to ameliorate memory deficits, shift PTSD-induced recall of stressful memories to an extinction path, or regulate other memory processes.