Dementia Research Articles

Effects of immersive virtual reality stimulation and/or multicomponent physical exercise on cognitive and functional performance in hospitalized older patients with severe functional dependency: study protocol for a randomized clinical trial

BackgroundHospital-associated functional decline affects nearly one-third of the hospitalized older adults. The aim of this trial is to investigate the effect of a cognitive stimulation intervention provided via immersive virtual reality (IVR), with or without a multicomponent physical exercise intervention (ME) in hospitalized patients aged 75 or older with severe functional dependency at admission (Barthel Index < 60 points).MethodsThis clinical randomized controlled trial will be conducted in the Acute Geriatric Unit of a tertiary hospital in Spain. A total of 212 acute patients will be enrolled according to the following criteria: age ≥ 75, Barthel Index < 60, able to collaborate, expected length of stay ≥ 5 days, absence of clinical instability and severe dementia (Global Deterioration Scale 7) or other end-stage disease. Patients will be randomly assigned to a control group (CG) or any of the three intervention groups (IG): IVR, ME, or IVR + ME. The IVR group will watch ad-hoc videos showing Spanish regional landscapes and villages, approximately 4 min per day for three consecutive days. The ME group will undergo aerobic and strength exercise for progressive training of the upper and lower limbs. The IVR + ME group will do both cognitive and physical intervention. The primary outcomes will be cognitive and physical measures at discharge. Mood, quality of life, isometric strength, and acceptance of IVR will be also assessed.DiscussionThis project has the potential to enhance physical and psychological well-being of patients with severe functional dependency hospitalized for acute conditions, using technology. Virtual reality is expected to be favourably perceived by hospitalized older adults. This intervention represents a novelty in the geriatric patients’ care, comprising IVR and/or ME dispensed within the patient’s room, and including patients who are commonly excluded from research clinical trials.Trial registrationThis study was approved by the Navarra Clinical Research Ethics Committee on May 17th, 2023 (PI_2023/60). The trial is registered at ClinicalTrials.gov, registration number NCT06340282, 24th May 2024.

Social and emotional self-perception in people with mild to moderate Alzheimer disease compared to caregiver's perspective in Brazil.

There was limited evidence on the ability of people with Alzheimer disease (AD) to perceive their own emotions. We aimed to compare socioemotional self-perception in persons with mild and moderate AD to their caregivers' perspective. Cross-sectional assessment of people with mild (n=102) and moderate (n=59) AD and caregivers. Each participant and their caregivers completed the socioemotional questionnaire (SEQ); a 30-item rating scale assessing five dimensions of socioemotional cognition (empathy, emotion recognition, social conformity, antisocial behavior, sociability). We evaluated global cognition, awareness of disease, dementia severity, functionality, neuropsychiatric symptoms, and caregiver burden. Participants in the mild and moderate groups showed a similar pattern of socioemotional self-perception. They differed in the anger domain of the emotion recognition subscale, in the antisocial behavior dimension, and in the sociability subscale. In contrast, the caregivers' perspective of people with mild and moderate AD showed a significant difference in the emotion recognition domain for fear, disgust, and sadness. There were also significant differences in the empathy subscale for disgust and in the sociability subscale. Cognition was correlated with self-reported reduced perception in social conformity, antisocial behavior, and sociability. Awareness was correlated with emotion recognition, antisocial behavior, and sociability. Neuropsychiatric symptoms were correlated with empathy, emotion recognition, and social conformity. Significant differences were found between caregivers' perspectives of socioemotional functioning in people with mild and moderate AD. Meanwhile, there were minimal differences in self-perception between the mild and moderate groups.

Dexmedetomidine Attenuates Neuroinflammation-Mediated Hippocampal Neurogenesis Impairment in Sepsis-Associated Encephalopathy Mice through Central α2A-Adrenoceptor.

Sepsis-associated encephalopathy (SAE), one of the common complications of sepsis, is associated with higher ICU mortality, prolonged hospitalization, and long-term cognitive decline. Sepsis can induce neuroinflammation, which negatively affects hippocampal neurogenesis. Dexmedetomidine has been shown to protect against SAE. However, the potential mechanism remains unclear. In this study, we added lipopolysaccharide (LPS)-stimulated astrocytes-conditioned media (LPS-CM) to neural stem cells (NSCs) culture, which were pretreated with dexmedetomidine in the presence or absence of the α2-adrenoceptor antagonist yohimbine or the α2A-adrenoceptor antagonist BRL-44408. LPS-CM impaired the neurogenesis of NSCs, characterized by decreased proliferation, enhanced gliogenesis, and declined viability. Dexmedetomidine alleviated LPS-CM-induced impairment of neurogenesis in a dose-dependent manner. Yohimbine, as well as BRL-44408, reversed the effects of dexmedetomidine. We established a mouse model of SAE via cecal ligation and perforation (CLP). CLP-induced astrocyte-related neuroinflammation and hippocampal neurogenesis deficits, accompanied by learning and memory decline, which were reversed by dexmedetomidine. The effect of dexmedetomidine was blocked by BRL-44408. Collectively, our findings support the conclusion that dexmedetomidine can protect against SAE, likely mediated by the combination of inhibiting neuroinflammation via the astrocytic α2A-adrenoceptor with attenuating neuroinflammation-induced hippocampal neurogenesis deficits via NSCs α2A-adrenoceptor.

Mild behavioral impairment in people with mild cognitive impairment: Are the two conditions related?

Mild cognitive impairment (MCI) and mild behavioral impairment (MBI) are both considered potential prodromal stages of dementia, especially Alzheimer's disease. Previous literature has lacked specific information about MBI in individuals with MCI and associations of several aspects of both, MBI and MCI. Our aim was to investigate whether associations exist between aspects of MBI and aspects of cognitive performance in certain dimensions of the Montreal Cognitive Assessment (MoCA). We used baseline data from the double-blind randomized controlled intervention MCI-CCT-study. Current cognitive performance of individuals with MCI was measured with the MoCA. MBI was assessed with the MBI Shortscale (MBI short), which was administered through a self-report interview. Associations were assessed with Pearson correlations. Sensitivity analyses were conducted for gender and cognition. Group differences were examined with independent samples t-tests or Welch test. Significant correlations were considered in binary logistic regressions under control of covariates. There was no significant correlation between the current MoCA and MBI short scores in the total sample or in the gender-related analysis. Using dichotomized cognitive performance, significant correlations between MCI and MBI were revealed for individuals with lower MoCA scores. On the task level, several significant associations were identified between MoCA dimensions and MBI dimensions in the total sample and in the sensitivity analyses, also under control of covariates. Our findings support the hypothesis that with increasing cognitive decline, the association between MCI and MBI becomes stronger. Furthermore, a certain cut-off on the MoCA must be reached to identify a correlation.

Angioarchitectural alterations in the retina and choroid in frontotemporal dementia.

Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder that affects the frontal and temporal lobes of the brain, leading to cognitive decline and personality changes. The objective of this cross-sectional study was to characterize angioarchitectural changes in the retina and choroid of individuals with FTD compared to cognitively normal controls using optical coherence tomography (OCT) and OCT angiography (OCTA). Cross-sectional comparison of patients with FTD and controls with normal cognition. All participants underwent Mini-Mental State Examination (MMSE) at the time of imaging. Outcome measures included OCT parameters: retinal nerve fiber layer (RNFL) thickness, ganglion cell layer-inner plexiform layer (GC-IPL) thickness, central subfield thickness (CST), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI); and OCTA superficial capillary plexus parameters: foveal avascular zone (FAZ) area, 3x3mm and 6x6mm macular perfusion density (PD) and vessel density (VD), 4.5x4.5mm peripapillary capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equation analysis was used to account for the inclusion of 2 eyes from the same participant. 29 eyes of 19 patients with FTD and 85 eyes of 48 controls were analyzed. In FTD, 3x3mm macular PD (p = 0.02) and VD (p = 0.02) and CFI (p = 0.01) were reduced compared to controls. There was no difference in average 4.5x4.5mm CPD, RNFL thickness, GC-IPL thickness, CST, SFCT, CVI, FAZ, or 6x6mm VD or PD between FTD and controls (all p > 0.05); however, there was a trend toward lower macular 6x6mm PD and VD in patients with FTD. Decline of peripapillary and macular OCT and OCTA parameters merit further investigation as potential biomarkers for FTD detection. Noninvasive retinal and choroidal imaging may hold promise for earlier detection, and future longitudinal studies will clarify their role in monitoring of FTD.

Emerging trends in cognitive impairment and dementia among older populations in Asia: A systematic review.

Dementia and cognitive impairment rates in Asia have significant policy implications. Contrary to the existing literature, which primarily focused on the Western region, in this study, we provide novel insights into previously unexplored geographical contexts. We aimed to evaluate the prevalence of cognitive impairment and dementia in Asia. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched six bibliographic databases: Web of Science, Medline, Science Direct, Ovid, Google Scholar, and PubMed. We targeted cross-sectional studies on dementia and cognitive impairment in Asia, published between 2019-23. Our extensive search yielded 2593 original articles, of which 39 met eligibility criteria. This selection unveiled a significant rise in dementia and cognitive impairment prevalence in Asia, aligning now with trends observed in Western countries - a novel finding that challenges previous assumptions about regional prevalence disparities. The studies predominantly conducted in East Asia (n = 29), along with limited research from Southeast (n = 2), South (n = 7), and Central Asia (n = 1), underscore the geographical gaps in current research. This shift in prevalence patterns is potentially linked to demographic changes, urbanisation, environmental factors, ethnic diversity, and neuroimaging advancements. Identifying modifiable risk factors associated with dementia in these regions presents new avenues for prevention and intervention strategies. Current dementia research in Asia is concentrated in East Asia, with limited data from Southeast, South, and Central Asia. Comprehensive studies across all parts of Asia are crucial to establishing robust data collection methods and identifying modifiable risk factors. This can help manage and mitigate the growing burden of dementia in these societies.

Exploring the barriers to the development of organizational health literacy in health institutions to meet the needs of older patients from multiple perspectives: a mixed-methods study

BackgroundThe latest evidence on health literacy in China revealed that only 8% of individuals aged 65–69 years, a segment of the geriatric population, possess adequate health literacy levels, indicating a low level in China. Studies have demonstrated that improving the organizational health literacy of healthcare institutions is a crucial approach to addressing low health literacy among older patients.ObjectiveTo explore the obstacles hindering the advancement of organizational health literacy in healthcare institutions in meeting the needs of older patients.DesignA mixed-methods approach was employed to investigate both the status and barriers to the establishment of organizational health literacy within two healthcare institutions.ParticipantsParticipants included older individuals aged over 60, clinical staff, and managerial personnel from these two health institutions.MethodsThis research utilized the social-ecological model as its theoretical foundation and utilized a mixed-methods approach to examine the current status and challenges in developing organizational health literacy within healthcare institutions. Initially, a survey using a questionnaire (n = 178) was conducted among older patients to evaluate the establishment of organizational health literacy from their perspective. Following this, interviews (n = 22) were carried out with administrators, clinical personnel, and elderly patients to identify the barriers hindering the development of organizational health literacy within healthcare institutions.ResultsQuantitative research indicates that health institutions have been less accommodating to the requirements of older patients, with health information dissemination and communication emerging as the weakest areas. Qualitative investigations revealed three key influencing factors: patient-related factors, including physiological and cognitive decline, as well as low educational attainment among older patients; organizational factors, including inadequate clinical staff numbers, deficient long-term systematic training, and a digital divide resulting from health institutions’ digital advancements; and policy-related factors indicating a lack of regulations governing the establishment of organizational health literacy within healthcare institutions.ConclusionThe two most vulnerable aspects of OHL in medical institutions regarding the needs of older patients are health information and communication. The factors influencing the construction of OHL in medical institutions are multifaceted, encompassing micro, meso, and macro levels. At the macro level, it is essential for medical institutions to enhance leadership awareness of OHL and to incorporate its development into institutional strategic plans. At the meso-level, medical institutions should be made to optimize the medical environment for elderly patients and to prioritize health literacy training for medical staff. At the micro level, attention must be given to the characteristics and needs of elderly patients. Ultimately, by implementing a comprehensive construction of intervention strategies, the response ability of medical institutions to the needs of elderly patients can be enhanced.

Association of amyloid and cardiovascular risk with cognition: Findings from KBASE.

Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians. Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally. Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p<0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups. Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals. Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum.

Global brain activity and its coupling with cerebrospinal fluid flow is related to tau pathology.

Factors responsible for the deposition of pathological tau in the brain are incompletely understood. This study links macroscale tau deposition in the human brain to cerebrospinal fluid (CSF) flow dynamics using resting-state functional magnetic resonance imaging (rsfMRI). Low-frequency (<0.1Hz) resting-state global brain activity is coupled with CSF flow and potentially reflects CSF dynamics-related clearance. We examined the correlation between rsfMRI measures of CSF inflow and global activity (gBOLD-CSF coupling) as a predictor, interacting with amyloid beta (Aβ), of tau and cortical thickness (dependent variables) across Alzheimer's Disease Neuroimaging Initiative (ADNI) participants from cognitively unimpaired through mild cognitive impairment (MCI) and Alzheimer's disease (AD). Tau deposition in Aβ+ participants, accompanied by cortical thinning and cognitive decline, is associated with decreased gBOLD-CSF coupling. Tau mediates the relationship between coupling and thickness. Findings suggest that resting-state global brain activity and CSF movements comodulate Alzheimer's tau deposition, presumably related to CSF clearance. A non-invasive functional magnetic resonance imaging (fMRI) assessment of a CSF clearance-related process is carried out. Global brain activity is coupled with CSF inflow in human fMRI during resting state. Global fMRI-CSF coupling is correlated with tau in Alzheimer's disease (AD). This coupling measure is also associated with cortical thickness, mediated by tau.

Association between whole egg consumption and cognitive function in older adults: Birjand longitudinal aging study

OBJECTIVE: Egg consumption could reduce the chance of cognitive decline. We aimed to assess this possible protective effect using data from the Birjand longitudinal aging study (BLAS). METHODS: In this cross-sectional study, the association between number of whole eggs consumed per week and cognitive impairment was assessed on 1352 participants in the context of the first wave of BLAS conducted on September 2018 to April 2019. Six Item Cognitive Impairment Test (6-CIT), Mini-Mental State Examination (MMSE), Verbal Fluency Test (VFT) and abbreviated mental test (AMT) questionnaires were used to assess the cognitive function. Analyses have been conducted using multiple logistic regression. RESULTS: Participants ate an average of 2.4 eggs per week. Older adults with moderate and high egg consumption (2–3 eggs/week and ≥4 eggs/week, respectively) performed better at 6-CIT (OR: 0.61, 95% CI: 0.46; 0.80; and 0.58, 95% CI: 0.41; 0.82), AMT (0.67, 95% CI: 0.52; 0.87; and 0.56, 95% CI: 0.39; 0.80) and all 4 cognitive tests combined (0.47, 95% CI: 0.30; 0.73; and 0.44, 95% CI: 0.24; 0.78). VFT was not associated, and MMSE score was only associated with high egg intake (0.53, 95% CI: 0.38; 0.74). High egg intake was more protective of cognitive decline (≥40%) than the moderate intake (30–40%). The significance of most associations disappeared after adjustment for confounders and covariates. CONCLUSIONS: In summary, the findings of this study suggest a potential inverse relationship, displaying an ascending trend, between weekly egg consumption and cognitive function among elderly Iranians.

The Health Equity Scholars Program: Fostering Culturally Competent and Successful Independent Investigators in Alzheimer's Disease and Related Dementia Research.

The Health Equity Scholars Program (HESP) addresses the critical need for a diverse, culturally competent workforce to study and treat older adults from underrepresented populations (URPs) with Alzheimer's disease and related dementias (AD/ADRD). The HESP offers tailored mentored training in AD/ADRD research concepts, aiming to develop successful independent researchers. It recruits Scholars from underrepresented backgrounds as well as those passionate about AD/ADRD health equity research. We (1) describe the fundamental elements of the HESP, and (2) present preliminary data from the HESP program evaluation results performed by an outside agency, pre-post participation surveys, and Scholar accomplishments. The HESP Scholars reported high rates of proficiency, satisfaction, and competency in nearly all evaluated areas, and have been successful in obtaining grants, promotions, and publications. These initial outcomes data suggest that the HESP is meeting its objective of diversifying the workforce in the field of AD/ADRD research and care. The Health Equity Scholars Program aims to cultivate a diverse and culturally competent workforce, who are well-prepared to study and treat underrepresented older adults with Alzheimer's disease and related dementias (AD/ADRD). The program provides tailored mentored training in AD/ADRD research concepts, with the goal of nurturing successful independent researchers. Rigorous evaluation processes for applications ensure the selection of highly qualified Scholars. The program includes tailored training activities such as seminars and grant writing workshops, and tracks Scholar achievements while undergoing annual external evaluation to enhance its training program iteratively.

Interconnected Pathways: Exploring Inflammation, Pain, and Cognitive Decline in Osteoarthritis

The relationship among inflammation, pain, and cognitive decline in osteoarthritis (OA) patients is complex and has not been sufficiently explored; therefore, we undertook this research to evaluate how OA-related inflammation and pain affect cognitive functions, as well as to examine the potential of urinary markers as indicators of these conditions. This study examined fifty OA patients through clinical and cognitive assessments, morphological analyses, urinary biomarkers, and bioinformatics. Morphologically, 24% of patients had moderate to high synovial inflammation, which was significantly correlated with depressive symptoms, pain intensity, and self-reported anxiety. The Montreal Cognitive Assessment indicated minimal decline in most patients but showed negative correlations with age and inflammation severity. Urinary TNF-α and TGF-β1 levels positively correlated with body mass index and pain and synovitis score and immune cell infiltration, respectively. In contrast, cartilage oligomeric matrix protein and C-telopeptides of type II collagen showed inverse correlations with pain duration and cognitive function, respectively. Distinct patient clusters with higher inflammation were identified and were associated with reported pain and depressive symptoms. Urinary TNF-α and TGF-β1 can serve as biomarkers reflecting inflammation and disease severity in OA. This study suggests that synovial inflammation may be linked to mental and cognitive health in some patient cohorts.

The temporal relation of physical function with cognition and the influence of brain health in the oldest-old.

Introduction Physical function and cognition seem to be interrelated, especially in the oldest-old. However, the temporal order in which they are related and the role of brain health remain uncertain. Methods We included 338 participants (mean age 93.1 years) from two longitudinal cohorts: The UCI 90+ Study and EMIF-AD 90+ Study. We tested the association between physical function (Short Physical Performance Battery, gait speed and handgrip strength) at baseline with cognitive decline (MMSE, memory tests, Animal fluency, Trail Making Test (TMT) A and Digit Span Backward), and the association between cognition at baseline with physical decline (mean follow-up 3.3 years). We also tested whether measures for brain health (hippocampal, white matter lesion and gray matter volume) were related to physical function and cognition, and whether brain health was a common driver of the association between physical function and cognition by adding it as confounder (if applicable). Results Better performance on all physical tests at baseline was associated with less decline on MMSE, memory and TMT A. Conversely, fewer associations were significant but better scores on memory, TMT A and Digit Span Backward were associated with less physical decline. When adding measures for brain health as confounder, all associations stayed significant except for memory with gait speed decline. Discussion In the oldest-old, physical function and cognition are strongly related, independently of brain health. Also, the association between physical function and cognitive decline is more pronounced than the other way around, suggesting a potential for slowing cognitive decline by optimizing physical function.

Cognitive decline in Cushing's syndrome: A systematic review.

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.

Novel Piperazine Based Compounds Target Alzheimer's Disease Relevant Amyloid β42 and Tau Derived Peptide AcPHF6, and the Lead Molecule Increases Viability in the Flies Expressing Human Tau Protein.

Alzheimer's disease (AD) is the leading form of dementia in the United States and the world. The pathophysiology of AD is complex and multifaceted. Accumulation of senile plaques and neurofibrillary tangles (NFTs) are hallmarks of AD. The aggregation of amyloid β (senile plaques) and tau tangles (NFTs) results in the death of neurons in the cortex and hippocampus, which manifests itself in cognitive decline and memory loss. Current therapies rely on conventional approaches that have only treated the underlying symptoms without disease modification. Data from clinical studies point to a complex role of amyloid β (Aβ) in a way that enhances the tau phenotype throughout the disease process. To address the co-pathogenic role of Aβ and tau, we undertook development of multitarget compounds aiming at both tau and Aβ to slow or stop disease progression and provide neuroprotection. Here, we demonstrate a dose-dependent effect of the novel test compounds that inhibit aggregation of AcPHF6 (a shorter version of tau protein) and Aβ1-42 peptides in thioflavin T fluorescent assays. The compounds were also shown to disaggregate preformed aggregates dose dependently. To further validate these findings, circular dichroism experiments were carried out to examine the nature of inhibition. Additionally, transmission electron microscopy experiments were carried out to gain insights into the morphologies of aggregates obtained from dose-dependent inhibition of AcPHF6 and Aβ1-42 as well as dissociation of preformed aggregates from these peptides. Compounds D-687 and D-688 reversed Aβ1-42 induced toxicity in SH-SH5Y cells, significantly demonstrating neuroprotective properties. Finally, in a study with Drosophila melanogaster expressing human tau protein isoform (2N4R) in all the neurons, compound D-688 significantly increased the survival of flies compared to vehicle treated controls. Future studies will further examine the neuroprotective properties of these lead compounds in various animal models.

Behavioural and neuronal substrates of serious game-based computerised cognitive training in cognitive decline: randomised controlled trial.

Investigations of computerised cognitive training (CCT) show heterogeneous results in slowing age-related cognitive decline. To comprehensively evaluate the effectiveness of serious games-based CCT, integrating control conditions, neurophysiological and blood-based biomarkers, and subjective measures. In this bi-centric randomised controlled trial with parallel groups, 160 participants (mean age 71.3 years) with cognitive impairment ranging from subjective decline to mild cognitive impairment, were pseudo-randomised to three arms: an intervention group receiving CCT immediately, an active control (watching documentaries) and a waitlist condition, which both started the CCT intervention after the control period. Both active arms entailed a 3-month intervention period comprising a total of 60 at-home sessions (five per week) and weekly on-site group meetings. In the intervention group, this was followed by additional 6 months of CCT, with monthly booster sessions to assess long-term training effects. Behavioural and subjective changes were assessed in 3-month intervals. Biological effects were measured by amyloid blood markers and magnetic resonance imaging obtained before and after training. Adherence to the training protocol was consistently high across groups and time points (4.87 sessions per week). Domain-specific cognitive scores showed no significant interaction between groups and time points. Significant cognitive and subjective improvements were observed after long-term training. Voxel-based morphometry revealed no significant changes in grey matter volume following CCT, nor did amyloid levels moderate its effectiveness. Our study demonstrates no benefits of 3 months of CCT on cognitive or biological outcomes. However, positive effects were observed subjectively and after long-term CCT, warranting the inclusion of CCT in multicomponent interventions.

Elevated serum sodium is linked to increased amyloid-dependent tau pathology, neurodegeneration, and cognitive impairment in Alzheimer's disease.

Vascular dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). While sodium is essential for maintaining vascular function, its role in AD pathology remains unclear. We included 353 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), assessing serum sodium levels, cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, magnetic resonance imaging (MRI), and cognitive function. An independent sample (N = 471) with available CSF sodium-related proteins and AD biomarkers was also included. Associations between serum sodium levels and AD pathology, neurodegeneration, and cognition were evaluated using linear regression models. Spearman's correlation analyses assessed the relationships between CSF sodium-related proteins and AD biomarkers. Higher serum sodium levels were associated with increased AD pathology, reduced hippocampal volume, and greater cognitive decline (all p < 0.05). The relationship between serum sodium and amyloid PET was evident in several AD-susceptible brain regions, including the neocortex and limbic system. Individuals with high serum sodium exhibited higher tau pathology, lower hippocampal volume, and more severe cognitive decline per unit increase in amyloid PET compared to those with low serum sodium (all p < 0.05). Among the 14 CSF sodium-related proteins, which were inter-correlated, six were significantly correlated with CSF AD pathology and amyloid PET, while two were correlated with hippocampal volume and cognitive function, with sodium channel subunit beta-2 (SCN2B) and sodium channel subunit beta-3 (SCN3B) showing the strongest correlations. These findings underscore the crucial role of serum sodium in AD progression, highlighting a potential network of sodium dysregulation involved in AD pathology. Targeting sodium may offer a novel therapeutic approach to slowing AD progression, particularly by impeding the progression of amyloid-related downstream events.

Magnetic resonance diffusion tensor imaging for detecting the cerebral microstructure changes in patients with CSVD -induced mild cognitive impairment.

Cerebral small vessel disease (CSVD)-induced mild cognitive impairment (MCI) has been linked to cognitive decline. Brain atrophy is considered the most common change in MCI patients, which can be measured by diffusion tensor imaging (DTI). The study aimed to explore the relationship between DTI parameters and cognitive function in CSVD patients with MCI. This retrospective analysis involved 185 patients with CSVD, comprising 87 cases with MCI and 98 cases without MCI (NMCI). Analyses of demographic and clinical characteristics were conducted. DTI-measured fractional anisotropy (FA) and mean diffusivity (MD) in the hippocampus and entorhinal cortex regions were examined. The diagnostic values were determined using receiver-operative-curve (ROC) analysis, with the Youden Index identifying optimum sensitivity and specificity. Correlations between Montreal cognitive assessment (MoCA) scores and FA or MD in MCI patients were further assessed. No significant differences were observed in demographic and clinical characteristics between MCI and NMCI groups (all p>0.05), except for diabetes prevalence (p=0.011). Notably, the ROC analysis highlighted the diagnostic potential of FA, showing the maximum area under the curve values (Hippocampus-Left: 0.76; Hippocampus-Right: 0.66; Entorhinal cortex-Left: 0.62; Entorhinal cortex-Right: 0.64). MD exhibited a significant negative correlation with MoCA scores (Hippocampus-Left: r=-0.58, p<0.001; Hippocampus-Right: r=-0.41, p<0.001; Entorhinal cortex-Left: r=-0.49, p<0.001; Entorhinal cortex-Right: r=-0.27, p<0.001), while FA showed a significant positive correlation (Hippocampus-Left: r=0.51, p<0.001; Hippocampus-Right: r=0.31, p=0.004; Entorhinal cortex-Left: r=0.35, p<0.001; Entorhinal cortex-Right: r=0.38, p<0.001). The study demonstrates the diagnostic value of DTI parameters in CSVD patients with MCI, emphasizing the associations between microstructural brain changes and cognitive function.

40 Hz light preserves synaptic plasticity and mitochondrial function in Alzheimer’s disease model

Alzheimer’s disease (AD) is the most prevalent type of dementia. Its causes are not fully understood, but it is now known that factors like mitochondrial dysfunction, oxidative stress, and compromised ion channels contribute to its onset and progression. Flickering light therapy has shown promise in AD treatment, though its mechanisms remain unclear. In this study, we used a rat model of streptozotocin (STZ)-induced AD to evaluate the effects of 40 Hz flickering light therapy. Rats received intracerebroventricular (ICV) STZ injections, and 7 days after, they were exposed to 40 Hz flickering light for 15 min daily over seven days. Cognitive and memory functions were assessed using Morris water maze, novel object recognition, and passive avoidance tests. STZ-induced AD rats exhibited cognitive decline, elevated reactive oxygen species, amyloid beta accumulation, decreased serotonin and dopamine levels, and impaired mitochondrial function. However, light therapy prevented these effects, preserving cognitive function and synaptic plasticity. Additionally, flickering light restored mitochondrial metabolites and normalized ATP-insensitive mitochondrial calcium-sensitive potassium (mitoBKCa) channel activity, which was otherwise downregulated in AD rats. Our findings suggest that 40 Hz flickering light therapy could be a promising treatment for neurodegenerative disorders like AD by preserving synaptic and mitochondrial function.

Amyloid-beta antibody treatment in Alzheimer's disease : An update on recent data and outlook on implementation in clinical routine.

Amyloid-beta (Aβ) antibody treatment has emerged as apromising approach for the treatment of Alzheimer's disease (AD), targeting the accumulation of Aβ plaques, which are ahallmark of the disease. This review provides an update on recent clinical trial data, highlighting the efficacy and safety of various antibodies targeting Aβ. Recent trials have demonstrated that certain Aβ antibodies can reduce amyloid plaques and slow cognitive decline in patients with early AD. Key findings from trials of drugs are discussed, including their mechanisms of action, dosing regimens, and observed side effects. The potential for Aβ antibody therapy to be integrated into routine clinical practice is also explored. While Aβ antibody therapy represents asignificant advancement in AD treatment, ongoing research is needed to optimize their use and understand their long-term impact. This review underscores the importance of personalized medicine in AD and the need for continued innovation in therapeutic strategies.