[Clinical and psychometric characteristics of cognitive and negative disorders in schizophrenia]. / Klinicheskie i psikhometricheskie osobennosti kognitivnykh i negativnykh rasstroistv pri shizofrenii.

OBJECTIVE: To establish the characteristics of clinical manifestations and cognitive tests in patients with schizophrenia, with a predominance of cognitive and negative disorders. MATERIAL AND METHODS: We examined 76 patients, 66 in the main group, 10 in the comparison group, who were treated in Psychiatric Hospital No. 1 and Psychiatric Hospital No. 4 (Moscow). Clinical-psychopathological, psychometric and statistical methods were used. Features of cognitive functioning were studied using the Frontal Assessment Battery (FAB) and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS). Emotional intelligence scores were assessed using the Ekman Face Emotion Recognition (EFER) test. RESULTS: Patients with schizophrenia showed dominance of one of 3 types of deficit symptoms: cognitive, emotional, and volitional. Cognitive functions were significantly reduced in patients with schizophrenia when compared with the comparison group (mean FAB score (M±SD) 13.44±2.97 in patients with schizophrenia vs. 16.10±1.70 in the comparison group; t=4.10; p<0.001). Cognitive functions were particularly reduced in patients with volitional deficit (mean EFER total score 42.40±9.0 in patients with volitional deficit vs. 47.21±633 in patients with cognitive deficit; t=2.12; p=0.039; mean FAB score 12.83±3.29 in patients with volitional deficit vs. 16.10±1.70 in the comparison group; t=4.24; p<0.001; mean ECAS score specific to ALS 78.80±9.07 in patients with volitional deficit vs. 84.50±6.71 in the comparison group; t=2.18; p=0.034). CONCLUSION: The greatest contribution to the development of cognitive disorders in schizophrenia is made by dysfunction of frontal (especially) and temporal cortex. Executive functions, speech skills and verbal fluency are most severely damaged.

Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.

An analysis of factors influencing cognitive dysfunction among older adults in Northwest China based on logistic regression and decision tree modelling.

BACKGROUND: Cognitive dysfunction is one of the leading causes of disability and dependence in older adults and is a major economic burden on the public health system. The aim of this study was to investigate the risk factors for cognitive dysfunction and their predictive value in older adults in Northwest China. METHODS: A cross-sectional study was conducted using a multistage sampling method. The questionnaires were distributed through the Elderly Disability Monitoring Platform to older adults aged 60 years and above in Northwest China, who were divided into cognitive dysfunction and normal cognitive function groups. In addition to univariate analyses, logistic regression and decision tree modelling were used to construct a model to identify factors that can predict the occurrence of cognitive dysfunction in older adults. RESULTS: A total of 12,494 valid questionnaires were collected, including 2617 from participants in the cognitive dysfunction group and 9877 from participants in the normal cognitive function group. Univariate analysis revealed that ethnicity, BMI, age, educational attainment, marital status, type of residence, residency status, current work status, main economic source, type of chronic disease, long-term use of medication, alcohol consumption, participation in social activities, exercise status, social support, total scores on the Balanced Test Assessment, total scores on the Gait Speed Assessment total score, and activities of daily living (ADL) were significantly different between the two groups (all P < 0.05). According to logistic regression analyses, ethnicity, BMI, educational attainment, marital status, residency, main source of income, chronic diseases, annual medical examination, alcohol consumption, exercise status, total scores on the Balanced Test Assessment, and activities of daily living (ADLs) were found to influence cognitive dysfunction in older adults (all P < 0.05). In the decision tree model, the ability to perform activities of daily living was the root node, followed by total scores on the Balanced Test Assessment, marital status, educational attainment, age, annual medical examination, and ethnicity. CONCLUSIONS: Traditional risk factors (including BMI, literacy, and alcohol consumption) and potentially modifiable risk factors (including balance function, ability to care for oneself in daily life, and widowhood) have a significant impact on the increased risk of cognitive dysfunction in older adults in Northwest China. The use of decision tree models can help health care workers better assess cognitive function in older adults and develop personalized interventions. Further research could help to gain insight into the mechanisms of cognitive dysfunction and provide new avenues for prevention and intervention.

[Early cognitive rehabilitation for patients with severe neurological impairment]. / Prise en charge cognitive précoce des patients cérébrolésés sévères.

Improving the state and future of patients severely impaired following brain injury is at the heart of early rehabilitation, established from the first days of hospitalization. For cognitive deficits, this management involves several challenges, related to hospital conditions and to the patients' capacities during the acute phase. A relevant intervention can be provided, as long as it involves an assessment adapted to these particularities and a rehabilitation targeting the most limiting deficits at this stage. These findings, discussed in the light of our clinical experience and current knowledge in the field, have yet to be scientifically tested since randomized clinical trials are still lacking. The integration of new technologies to facilitate the bedside work presents another prospect for the future.

Améliorer sans délai l'état et le devenir des patients sévèrement touchés par une lésion cérébrale constitue l'essence de la rééducation précoce, instaurée dès les premiers jours de l'hospitalisation. Pour les aspects cognitifs, cette prise en charge comporte plusieurs défis, liés aux conditions hospitalières et aux capacités des patients. Une intervention pertinente peut être pratiquée, sous réserve d'une évaluation adaptée à ces particularités et d'une rééducation ciblant les déficits les plus limitants à ce stade. Ces constats, discutés à la lumière de notre expérience clinique et des connaissances actuelles, doivent encore être prouvés scientifiquement car les essais cliniques randomisés manquent cruellement. L'intégration des nouvelles technologies pour faciliter le travail au chevet des patients constitue une autre perspective d'avenir.

Prevalence of Motoric Cognitive Risk Syndrome Among Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for policymakers planning health and social care policies. METHOD: Web of Science, PubMed, and Cochrane Library databases were searched for cross-sectional, prospective cohort, or population-based longitudinal studies of community-dwelling older adults aged ≥60 years with MCR from inception of the database through December 18, 2021. RESULTS: Seventeen studies were included. Pooled prevalence of MCR was found to be 10% (95% confidence interval [8%, 12%], I2 = 98.4%). Results of a subgroup analysis revealed a combined prevalence of MCR of 8.2% in males and 9.2% in females. Pooled prevalence of MCR was 9.7% in Asia and 10.2% in other regions. CONCLUSION: Prevalence of MCR in community-dwelling older adults is high. Our research may improve the epidemiological understanding of MCR, draw attention to older adults with MCR, and thus promote research of MCR and the formulation of relevant public health policies. With early identification and intervention of MCR, cognitive function can be improved, and the onset of dementia can be delayed or prevented. [Journal of Gerontological Nursing, 50(4), 16-24.].

Protocol for a construct and clinical validation study of MyCog Mobile: a remote smartphone-based cognitive screener for older adults.

INTRODUCTION: Annual cognitive screening in older adults is essential for early detection of cognitive impairment, yet primary care settings face time constraints that present barriers to routine screening. A remote cognitive screener completed on a patient's personal smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices and increase early detection of cognitive decline. MyCog Mobile is a promising new remote smartphone-based cognitive screening app for primary care settings. We propose a combined construct and clinical validation study of MyCog Mobile. METHODS AND ANALYSIS: We will recruit a total sample of 300 adult participants aged 65 years and older. A subsample of 200 healthy adult participants and a subsample of 100 adults with a cognitive impairment diagnosis (ie, dementia, mild cognitive impairment, cognitive deficits or other memory loss) will be recruited from the general population and specialty memory care centres, respectively. To evaluate the construct validity of MyCog Mobile, the healthy control sample will self-administer MyCog Mobile on study-provided smartphones and be administered a battery of gold-standard neuropsychological assessments. We will compare correlations between performance on MyCog Mobile and measures of similar and dissimilar constructs to evaluate convergent and discriminant validity. To assess clinical validity, participants in the clinical sample will self-administer MyCog Mobile on a smartphone and be administered a Mini-Cog screener and these data will be combined with the healthy control sample. We will then apply several supervised model types to determine the best predictors of cognitive impairment within the sample. Area under the receiver operating characteristic curve, accuracy, sensitivity and specificity will be the primary performance metrics for clinical validity. ETHICS AND DISSEMINATION: The Institutional Review Board at Northwestern University (STU00214921) approved this study protocol. Results will be published in peer-reviewed journals and summaries provided to the study's funders.

[The reversible share of cognitive deficits in older adults]. / La part réversible des déficits cognitifs chez les seniors.

Cognitive performance of older adults is very often inferior to that of younger adults on a variety of laboratory tests assessing basic functions such as memory, inhibition, or attention. Classic hypotheses and theories share the idea that these cognitive deficits are irreversible, due to profound cerebral changes. In this review article, we develop a more positive conception of aging, according to which cognitive deficits are not all irreversible, and can even be partially if not completely reversible. To this end, we present some of the most illustrative research on the reversibility of the effects of aging on cognition. We show how subtle contextual manipulations can change older adults' motivation and strategy, which improve their cognitive performance. We also show that guidance toward the selection of the most appropriate strategy, whether explicit as in selectivity paradigms or implicit as in dual-task procedures, can increase older adults' cognitive performance. We finally describe the hypotheses and theories that both account for low cognitive performance in old age and ways to reverse the effects of cognitive aging.

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract.

Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.

Association of 8-hydroxy-2'-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study.

BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.

α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway.

Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we investigated the pathological impact of αSyn on hippocampal neurons. We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients. In vivo, cofilin pathology is present concomitantly with synaptic impairment and cognitive dysfunction. Rods generation prompted by αSyn involves the co-action of the cellular prion protein (PrPC) and the chemokine receptor 5 (CCR5). Importantly, we show that CCR5 inhibition, with a clinically relevant peptide antagonist, reverts dendritic spine impairment promoted by αSyn. Collectively, we detail the cellular and molecular mechanism through which αSyn disrupts hippocampal synaptic structure and we identify CCR5 as a novel therapeutic target to prevent synaptic impairment and cognitive dysfunction in LBD.

Alterations in brain functional connectivity in patients with mild cognitive impairment: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD] = -.56; p < .001), left prefrontal to left occipital cortex (SMD = -.68; p < .001), and right prefrontal to left occipital cortex (SMD = -.53; p < .001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.

Comparison of cognitive performance measures in individuals with systemic lupus erythematosus.

OBJECTIVE: Cognitive impairment is a common complaint in SLE, but approaches to measuring cognitive performance objectively vary. Leveraging data collected in a population-based cohort of individuals with validated SLE, we compared performance and potential impairment across multiple measures of cognition. METHODS: During a single study visit (October 2019-May 2022), times to complete the Trail Making Test B (TMTB; N=423) were recorded; potential impairment was defined as an age-corrected and education-corrected T-score <35 (>1.5 SD longer than the normative time). A clock drawing assessment (CLOX; N=435) with two parts (free clock draw (CLOX1) and copy (CLOX2)) was also performed (score range: 0-15; higher scores=better performance); potential impairment was defined as CLOX1 <10 or CLOX2 <12. Fluid cognition (N=199; in-person visits only) was measured via the National Institutes of Health (NIH) Toolbox Fluid Cognition Battery and expressed as age-corrected standard scores; potential impairment was defined by a score <77.5 (>1.5 SD lower the normative score). RESULTS: Participants (mean age 46 years; 92% female; 82% black) had a median (IQR) TMTB time of 96 (76-130) s; median (IQR) CLOX1 and CLOX2 scores of 12 (10-13) and 14 (13-15); and a mean (SD) fluid cognition standard score of 87.2 (15.6). TMTB time and fluid cognition score (ρ=-0.53, p<0.001) were the most highly intercorrelated measures. Overall, 65%, 55% and 28% were potentially impaired by the TMTB test, CLOX task and NIH Toolbox Fluid Cognition Battery, respectively. While there was overlap in potential impairment between TMTB and CLOX, more than half (58%) had impairment by only one of these assessments. Few (2%) had impairment in fluid cognition only. CONCLUSION: The TMTB, CLOX and NIH Fluid Cognition Battery each provided unique and potentially important information about cognitive performance in our SLE cohort. Future studies are needed to validate these measures in SLE and explore interventions that maintain or improve cognitive performance in this population.

Structure and features of psychopathological symptoms in forced migrants and internally displaced persons.

OBJECTIVE: Aim: To study the structure and characteristics of psychopathological symptoms in FM who left Ukraine as a result of the full-scale armed aggression of the Russian Federation against Ukraine, and internally displaced persons, in a comparative aspect. PATIENTS AND METHODS: Materials and Methods: Examination was performed in compliance with the principles of biomedical ethics, based on informed consent. Research was provided on the basis of the Ternopil Regional Clinical Psychoneurological Hospital. Inclusion criteria were women who were forced to leave the territory of Ukraine as a result of hostilities after February 24, 2022, and who left for temporary residence in the territory of the Republic of Poland (Poland) (FM), and women who were temporarily relocated within Ukraine in connection with connection with hostilities (IDP). Exclusion criteria from the study were presence of language disorders, pronounced cognitive disorders, severe somatic condition. The examination was organized by the method of a semi-structured clinical interview according to the developed by us protocol and was conducted remotely. During the examination, depressive, anxiety-phobic, asthenic and dyssomnic disorders, addictive behavior and symptoms of PTSDwere identified and verified. Statistical and mathematical processing a was carried out using Fisher's exact test. RESULTS: Results: The data we obtained indicate a significant spread of psychopathological symptoms in FM and IDP. CONCLUSION: Conclusions: FM and IDP are characterized by a high incidence of psychopathological symptoms. The most frequent were: depressed mood (FM - 67.2%, IDP - 58.5%), feelings of anxiety and fear (FM -52.5%, IDP - 43.6%), obsessive thoughts (FM - 58.9 %, IDP - 49.5%).

Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI.

Incidence and predictors of post-stroke cognitive impairment among patients admitted with first stroke at tertiary hospitals in Dodoma, Tanzania: A prospective cohort study.

INTRODUCTION: Stroke survivors develop cognitive impairment, which significantly impacts their quality of life, their families, and the community as a whole but not given attention. This study aims to determine the incidence and predictors of post-stroke cognitive impairment (PSCI) among adult stroke patients admitted to a tertiary hospital in Dodoma, Tanzania. METHODOLOGY: A prospective cohort study was conducted at tertiary hospitals in the Dodoma region, central Tanzania. A sample size of 158 participants with the first stroke confirmed by CT/MRI brain aged ≥ 18 years met the criteria. At baseline, social-demographic, cardiovascular risks and stroke characteristics were acquired, and then at 30 days, participants were evaluated for cognitive functioning using Montreal Cognitive Assessment (MoCA). Key confounders for cognitive impairment, such as depression and apathy, were evaluated using the Personal Health Questionnaire (PHQ-9) and Apathy Evaluation Scale (AES), respectively. Descriptive statistics were used to summarise data; continuous data were reported as Mean (SD) or Median (IQR), and categorical data were summarised using proportions and frequencies. Univariate and multivariable logistic regression analysis was used to determine predictors of PSCI. RESULTS: The median age of the 158 participants was 58.7 years; 57.6% of them were female, and 80.4% of them met the required criteria for post-stroke cognitive impairment. After multivariable logistic regression, left hemisphere stroke (AOR: 5.798, CI: 1.030-32.623, p = 0.046), a unit cm3 increase in infarct volume (AOR: 1.064, 95% CI: 1.018-1.113, p = 0.007), and apathy symptoms (AOR: 12.259, CI: 1.112-89.173, p = 0.041) had a significant association with PSCI. CONCLUSION: The study revealed a significant prevalence of PSCI; early intervention targeting stroke survivors at risk may improve their outcomes. Future research in the field will serve to dictate policies and initiatives.

[Better assessment, better care: Quetci, a questionnaire for assessing cognitive disorders in nursing practice]. / Mieux évaluer, mieux soigner : le Quetci, un questionnaire d'évaluation des troubles cognitifs IDE.

Cognitive disorders can have significant repercussions on the quality of care and daily life for patients. We have developed a new tool specifically designed for nursing practice to identify these problems in patients with brain tumors. The Cognitive Impairment Assessment Questionnaire for nursing practice is an objective, quick and easy-to-administer tool that is readily accepted by patients.

Evaluating the effect of rapamycin treatment in Alzheimer's disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol.

BACKGROUND: Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The "Evaluating Rapamycin Treatment in Alzheimer's Disease using Positron Emission Tomography" (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer's disease. METHODS: ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer's disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. DISCUSSION: The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer's disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06022068, date of registration 2023-08-30.

Risks and benefits of hormone therapy after menopause for cognitive decline and dementia: A conceptual review.

OBJECTIVE: The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence. METHODS: We 1) provide a brief history of the evidence, 2) discuss some of the interpretations of the evidence, 3) discuss the importance of age at menopause, type of menopause, and presence of vasomotor symptoms, and 4) provide some clinical recommendations. RESULTS: The evidence and the beliefs about hormone therapy and dementia have changed over the last 30 years or more. Five recent observation studies suggested that hormone therapy is associated with an increased risk of dementia, and the association appears not to change with the timing of initiation of therapy. These harmful associations may be explained by a causal effect of hormone therapy on the brain or by several confounding mechanisms. We suggest that the use of hormone therapy should be customized for different subgroups of women. It may be important to subgroup women based on age at onset of menopause, type of menopause, and presence or absence of vasomotor symptoms. In addition, the effects may vary by type, dose, route, and duration of administration of estrogens and by the concurrent use of progestogens. DISCUSSION: The relation of hormone therapy with the risk of dementia is complex. Hormone therapy may have beneficial, neutral, or harmful effects on the brain. Hormone therapy should be guided by the clinical characteristics of the women being treated.

Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.