Journal of Alzheimer's disease reports最新文献

Background: Social isolation significantly heightens the risk of dementia among the elderly. Maintaining social engagement has been proposed as a potential strategy to attenuate age-related cognitive decline.

Objective: This study investigates whether social interaction with young conspecifics could improve cognitive function in aged mice with chronic social isolation.

Methods: Twenty-month-old male C57BL/6 mice with long-term social isolation were randomly assigned to either cohousing with 3-month-old young mice or continued isolation for two months. Cognitive function was assessed using Y-maze spontaneous alternation and fear conditioning tests. Synaptic integrity and pathological markers were evaluated through western blotting and immunofluorescence.

Results: Cohoused mice exhibited significantly enhanced novel arm exploration in the Y-maze and improved contextual fear memory compared to isolated controls. Molecular analyses revealed increased synapsin-1 expression and decreased tau phosphorylation at Ser214 in the cohousing group. Immunofluorescence demonstrated greater astrocyte density in the dentate gyrus of cohoused mice.

Conclusions: Our findings demonstrate that social interaction with young counterparts can rescue isolation-induced cognitive deficits in aged mice, potentially through mechanisms involving tau phosphorylation regulation and synaptic protein restoration. These results provide preclinical evidence supporting social intervention strategies for preventing cognitive decline in socially isolated elderly individuals.

A middle-aged female with family history of early-onset dementia presented with progressive amnesia, behavioral dysregulation, and myoclonus. Workup revealed pathogenic PSEN1 variant and intermediate HTT allele (30 CAG repeats). This case illustrates that motor symptoms should not be neglected in early-onset familial Alzheimer's disease (EOFAD). Moreover, hyperkinetic phenomenology does not reliably differentiate EOFAD and Huntington's disease (HD) due to the possibility of co-occurring mutations. Patients undergoing EOFAD evaluation should be screened for HD as well. Finally, this first case of presenilin mutation and abnormal huntingtin in the same patient suggests that EOFAD and HD can genetically co-occur.

Background: Olfactory impairment (OI) is an early symptom of neurodegenerative diseases (ND) and COVID-19 infection. Proteinopathies associated with ND include amyloid-β (Aβ), hyperphosphorylated τ (HPτ), α-synuclein (α-syn), and Tar DNA binding protein 43 (TDP43). It is unclear whether COVID-19 infection influences the listed proteinopathies in the olfactory bulb and tract (OB/OT) aggravating the OI.

Objective: To study proteinopathies associated with ND in the brain and OB/OT in 32 subjects with COVID-19 infection and 10 age- and gender-matched controls.

Methods: Postmortem brain tissue was assessed for various proteinopathies and the OB/OT for proteinopathies, inflammatory markers and a marker for severe acute respiratory syndrome coronavirus 2 spike protein.

Results: Twenty percent of control and 16% of COVID-19 subjects lacked proteinopathies in their OB/OT. HPτ was detected in OB/OT in 80% of controls and 81% of COVID-19 subjects, Aβ in 30% of controls and 16% of COVID-19 subjects. All controls lacked TDP43 in OB/OT, 40% displayed TDP43 in their brain. TDP43 was seen in the OB/OT in 38% of COVID-19 subjects, of whom 42% lacked TDP43 in the brain. Sixty percent of controls displayed α-syn in OB/OT and the brain, whereas 34% of COVID-19 subjects displayed α-syn in the OB/OT, of whom 36% lacked it in the brain.

Conclusions: All proteinopathies associated with ND were detected in OB/OT in COVID-19 patients whereas TDP43 was lacking in controls. Our results suggest that there might be an association between COVID-19 and TDP43 and α-syn in the OB/OT, which may explain the chronic OI.

Background: Sleep disorders are a significant risk factor for cognitive decline and Alzheimer's disease (AD). However, preclinical studies investigating the effects of sleep deprivation (SD) on cognition and synaptic proteins have produced inconsistent findings, hindering translational progress.

Objective: This systematic review and meta-analysis identify key factors moderating the effects of SD on cognition and synaptic proteins in rodent models.

Methods: Following PRISMA guidelines, we analyzed 21 eligible studies using meta-analysis, subgroup, meta-regression, and multilevel analyses to identify sources of experimental heterogeneity.

Results: SD significantly reduced synaptic proteins overall. While the global effect on cognition was not significant, subgroup analyses revealed robust cognitive impairment in Wistar rats undergoing fragmented sleep, particularly when assessed by Morris water maze or novel object recognition tests. Key synaptic proteins (PSD-95, synaptophysin) were consistently reduced in the hippocampus and prefrontal cortex.

Conclusions: Our comprehensive review synthesizes diverse studies, concluding that methodological choices are the primary drivers of heterogeneity in preclinical SD research. We provide evidence-based guidance for selecting appropriate rodent models, behavioral paradigms, and biochemical indicators to investigate the molecular mechanisms linking sleep disorders and cognitive decline. This work offers a significant framework to standardize and enhance the reliability of preclinical studies. By validating models that directly connect fragmented sleep-a condition common in AD patients-to synaptic pathology in vulnerable brain regions, our research strengthens the mechanistic link between sleep disturbance and cognitive impairment in AD and encourages a greater focus on this critical relationship for the readers of the Journal of Alzheimer's Disease Reports and AD researchers.

Background: The cognitive reserve (CR) theory aims to explain the disparity often observed between brain damage and its clinical manifestation.

Objective: To explore the CR theory in young-onset Alzheimer's disease (YOAD), a population not previously investigated in this context. The goal is to assess whether, similar to late-onset Alzheimer's disease (LOAD), a high CR delays diagnosis but may accelerate cognitive decline.

Methods: This is a retrospective study including 72 patients (ages: 46-64) who were diagnosed with possible YOAD. They were followed up for three years, using the Mini-Mental State Examination.

Results: Unlike the findings with LOAD, age of diagnosis of the YOAD did not correlate significantly with CR variables, years of education or family size. However, years of education predicted greater cognitive decline in the first year, and women showed increased deterioration. Family size showed inconsistent associations, highlighting its limitations.

Conclusions: In contrast to studies among LOAD, there was no significant correlation between age of diagnosis and CR among YOAD, suggesting that other mechanisms might be more influential than CR parameters in younger individuals. However, similar to LOAD, YOAD patients with higher education experienced faster disease progression, implying that diagnoses are frequently made when brain pathology is already severe. These findings reinforce the growing perspective that YOAD and LOAD may constitute distinct forms of AD, each with unique clinical and pathological features. They also underscore the urgent need for early detection tools and cognitive interventions to ease the challenges faced by these young patients.

Stathmin-2 (STMN2) levels decline in brains with transactive response DNA binding protein-43 (TDP-43) inclusions. TDP-43-related changes could extend to ocular structures, although vitreous STMN2 levels remain uncharacterized. This exploratory study analyzed 72 post-mortem brains and eyes depending on the presence or absence of TDP-43 inclusions in the brain and across neuropathological diagnostic groups (Alzheimer's disease [AD], chronic traumatic encephalopathy [CTE], AD and CTE, or neither). Results showed decreased vitreous STMN2 levels in TDP-43-positive cases but no association with diagnostic groups. Vitreous STMN2 was correlated with vitreous neurofilament light chain. Diminished vitreous STMN2 levels might indicate TDP-43-associated neurodegeneration.

Background: Emergency-department (ED) visits capture diagnostic data that could flag patients at heightened risk for Alzheimer's disease (AD) long before cognitive symptoms are formally recognized.

Objective: To examine how age and multimorbidity interact to predict AD and to test whether explainable machine learning enhances risk stratification using national ED data.

Methods: We analyzed 554,985 ED visits (2010-2014 National Emergency Department Sample) from adults ≥ 60 y. ICD-9-CM codes identified AD and 17 chronic conditions. Logistic regression estimated odds ratios (ORs) for single and combined comorbidities across five age bands. Predictive performance of logistic regression, decision tree, random forest and XGBoost was compared; Shapley Additive exPlanations (SHAP) interpreted model output.

Results: Urinary-tract infection (UTI; OR = 2.74), depression (1.93), hypothyroidism (1.68) and anemia (1.57) independently increased AD odds. Possessing all four "red-flag" conditions tripled risk (OR = 3.31), and each additional red-flag raised risk by 74%. Age showed a steep gradient: relative to 60-65 y, ORs climbed from 2.58 (66-70 y) to 25.8 (86-90 y; all p < 0.001). XGBoost performed best (AUC = 0.782; recall = 0.821), and SHAP confirmed age and red-flag multimorbidity as dominant predictors.

Conclusions: Routine ED codes reveal an age-dependent, dose-response relationship between specific multimorbidity clusters and AD. An interpretable XGBoost model accurately identifies high-risk patients, outlining a practical pathway for real-time cognitive-risk alerts in acute-care settings.

Background: Alzheimer's disease (AD) and other dementias are currently among the leading causes of morbidity and mortality worldwide.

Objective: To analyze the spatial and temporal behavior of AD mortality in Argentina.

Methods: This is a retrospective eco-epidemiological study based on the Death Certificate between 1997-2017 provided by the Ministry of Health. The specific death rates (SDRs) related to AD were calculated per 1000 deaths (AD*1000) by gender and age at departmental, provincial, and regional levels for the entire period. The Join Point method was applied to analyze the temporal trend, and SaTScan software was used to establish geospatial disparities.

Results: The highest SDRs were recorded in the departments, provinces, and regions located in the center of the country. At all administrative levels, female SDRs were almost twice as high as male SDRs. A positive secular trend in SDR was observed in all regions, with a significant increase between 1997-2002 and a less pronounced increase between 2003-2017. Clusters with the highest relative risks of AD death were located in the center of the country.

Conclusions: Following the global pattern, Argentina and all its regions show an increasing trend of AD deaths, with higher rates among women and older age groups. However, notable geospatial disparities attributed to population dynamics, migrations, and regional socioeconomic characteristics were identified.

Background: Early identification of risk factors is vital for the control of cognitive degenerative diseases, and sensory impairments could be potential candidate indicators.

Objective: To determine whether self-reported hearing loss (HL), olfactory dysfunction (OD), and gustatory dysfunction (GD) are associated with low cognitive performance.

Methods: Cross-sectional data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) were used. Data on participants' subjective hearing ability, olfactory and gustatory status were obtained from corresponding questionnaire datasets. Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The lowest quartile score of the four tests was used as the cutoff value to indicate low cognitive performance. Univariate and multivariate logistic regression analyses were conducted to investigate the association between sensory impairments and cognitive decline.

Results: The data of 1416 adults aged ≥60 years were included. Univariate logistic regression analyses showed that the association between self-reported HL, OD, GD, and low cognitive performance was significant across all four cognition tests. Multiple models of multivariate logistic regression adjusted by covariate factors were established and showed significant association between self-reported HL, OD, GD, and low cognitive performance.

Conclusions: Self-reported hearing loss, olfactory and gustatory dysfunction demonstrated significant associations with impaired cognitive performance in older adults. Multiple sensory impairments may lead to progressively worse cognitive performance.

Background: Precise estimates of the prevalence of Alzheimer's disease (AD), the distribution of demographic characteristics, comorbidities, treatment plans, insurance types, cost of treatment and survival probabilities at various time points are crucially important to advancing our understanding and for improving future AD research studies.

Objective: We analyzed two of the largest and high-quality medical databases, Oracle EHR Real-World Data and IQVIA. The results provide the most complete description of the AD patients in the US.

Methods: We present high-accuracy summary statistics of many important variables related to AD patients. Proportions, means and 95% confidence intervals were provided for all levels of the categorical and quantitative variables.

Results: We report high accuracy estimates of the overall survival probabilities for the first five years after initial diagnosis, drug treatments and patterns of use, demographics, insurance types, hospitalization duration, number of hospital visits, and a detailed list of comorbidities. We also report estimates of the annual total average cost of treatment per patient as well as itemized allocations for drugs, hospitalizations, surgery, and management costs.

Conclusions: We present the most complete, detailed and high-accuracy descriptive analysis of AD patients to date.