Journal of Alzheimer's Disease最新文献

Background: Women comprise approximately two-thirds of Alzheimer's disease cases.

Objective: This is the first known study to investigate the role of intersectionality between gender and other social determinants of health (SDOH) in the presentation of cognitive symptoms (i.e., being asymptomatic or symptomatic) among those with pathologically confirmed Alzheimer's disease.

Methods: We studied 3107 individuals with Alzheimer's disease neuropathology (ADNP) confirmed at autopsy. Asymptomatic ADNP was defined as the absence of a clinical diagnosis of mild cognitive impairment (MCI) or dementia before death (versus symptomatic: diagnosis of MCI/dementia). SDOH included gender, education, ethnoracial group, living alone, and primary language. Multivariable logistic regression tested associations between SDOH and asymptomatic ADNP (versus symptomatic); models were also stratified by gender.

Results: Women, Hispanics, those living alone, and more educated individuals were found to have higher odds of asymptomatic ADNP. Non-English speakers had lower odds of asymptomatic ADNP. Both women and men had higher odds of asymptomatic ADNP if Hispanic or living alone. In only women, non-English speakers had lower odds while in only men, more education was associated with higher odds of asymptomatic ADNP.

Conclusions: Gender, education, ethnicity, primary language, and living alone, and intersectionality of gender with primary language, may differentially influence MCI and dementia diagnosis prior to death among those with underlying ADNP. These findings emphasize the need for future Alzheimer's disease research to prioritize social determinants of brain health including their intersectionality with gender and how to inform targeted interventions.

Alzheimer's disease (AD) is a neurodegenerative disease with a long preclinical and prodromal stage near 20 years. The neuropathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and neuroinflammation, those lead to neuronal and synaptic loss. Important fact, oxidative stress participates in the AD development by promoting amyloid-β deposition, tau hyperphosphorylation. However, the inflammatory response and pyroptotic death are mediated by the aberrant expression of NLRP inflammasome activated caspase-1, which leads to cleavage pro-inflammatory cytokines such as pro-interleukin-1β and pro-IL-18. IL-1β, TNF-α, and IL-6 which amplify the neuroinflammation loop, are produce by activated microglia and astrocytes, that can serve as early diagnostic markers or therapeutic targets in AD. In this review, we summarize our current understanding of the role of inflammasome in the pathogenesis of AD, highlighting key issues that need to be addressed to improve the development of new therapies.

Shared cognitive decline among spouses remains in the early stages of being understood. In this commentary, we discuss Meng et al.'s systematic review and meta-analysis, which synthesizes the evidence for concordance of cognitive decline in couples. The study's methodology is robust and brings to light the challenges that persist within this field of research, namely the lack of specificity and standardization across outcomes and long-term follow-up. Here, we also situate the findings within the broader context of the many social influences on health and underscore the importance of dyadic preventive strategies and future longitudinal and mechanistic research.

Background: A 12-week randomized controlled trial demonstrated that brexpiprazole is efficacious for treating agitation in patients with dementia due to Alzheimer's disease.

Objective: To assess the long-term safety and tolerability of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease.

Methods: This 12-week, active-treatment (oral brexpiprazole 2 or 3 mg/day) extension trial ran from October 2018-September 2022 at 66 sites in Europe/US. Patients with agitation in dementia due to Alzheimer's disease in a care facility/community-based setting who completed the randomized trial were eligible (N = 259 enrolled/analyzed for safety; 88.4% completed). Stable Alzheimer's disease medications were permitted. The primary safety endpoint was the frequency and severity of treatment-emergent adverse events (TEAEs). Change in Cohen-Mansfield Agitation Inventory (CMAI) total score was an exploratory efficacy endpoint.

Results: Mean (SD) age was 74.3 (7.6) years, 145 patients (56.0%) were female, and 248 (95.8%) were White. TEAEs were reported by 67 patients (25.9%), most commonly headache (3.5%) and fall (2.3%). Most TEAEs were mild or moderate in severity; 5 patients (1.9%) reported a severe TEAE, including 3 severe falls attributed to tripping, misjudging sitting, or dehydration. Twelve patients (4.6%) discontinued due to TEAEs. No patients died. Mean CMAI total score improved by 9.1 points over 12 weeks.

Conclusions: Considering the randomized and extension trials together, brexpiprazole 2 or 3 mg was generally well tolerated for up to 24 weeks in elderly patients with agitation associated with dementia due to Alzheimer's disease. Patients showed continued improvement in agitation.

Clinicaltrials.gov identifier: NCT03594123 (registration date: July 11, 2018).

Background: Evidence on associations of remnant cholesterol (RC) and its variability with cognitive function is still lacking.

Objective: To explore the association of RC and its variability with cognitive function.

Methods: Participants were recruited from a population-based cohort, the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed by a standardized questionnaire from CHARLS, with domains of episodic memory and mental intactness. A linear mixed effects model was used to analyze the association of RC with cognitive function, along with its variability (calculated as standard deviation [SD], coefficient of variation [CV], variability independent of the mean [VIM]), with results expressed as β (95%CI). Potential subgroup differences in the association of RC and its variability with cognitive function were also explored.

Results: 4234 participants were eventually included, with mean (SD) age of 57.4 (8.0) years. Each 10 mg/dL increase in RC was associated with 0.053 (95%CI: 0.096, 0.009) points, 0.021 (95%CI: 0.042, 0.000) points, 0.032 (95%CI: 0.064, 0.001) points decrease in global cognitive function, episodic memory, and mental intactness scores, respectively. Compared with the first tertile (T1) group of RC variability (calculated as SD, VIM), T3 showed a lower level in global cognition and episodic memory after multivariate adjustment. The potential modification effects of educational level on RC and its variability in relation to cognitive function were also identified.

Conclusions: Among Chinese middle-aged and older adults, higher RC level were associated with worse cognitive function. Greater RC variability was also associated with worse cognitive performance, especially in memory function.

Background: Alzheimer's disease and related dementias (ADRD) frequently co-occur with comorbidities such as diabetes and cardiovascular diseases in elderly populations.

Objective: Utilize a life-course approach to identify genetic variants that are associated with the co-occurrence of ADRD and another comorbid condition.

Methods: Research data from African American participants of the Indianapolis-Ibadan Dementia Project (IIDP) linked with electronic medical record (EMR) data and genome-wide association study (GWAS) data were utilized. The age of onset for ADRD was obtained from longitudinal follow-up of the IIDP study. Age of onset for comorbid conditions was obtained from EMR. The analysis included 1177 African Americans, among whom 174 were diagnosed with ADRD. A semi-parametric marginal bivariate survival model was used to examine the influence of single nucleotide polymorphisms (SNPs) on dual time-to-event outcomes while adjusting for sex, years of education, and the first principal component of GWAS data.

Results: Targeted analysis of 20 SNPs that were reported to be associated with ADRD revealed that six were significantly associated with dual-disease outcomes, specifically congestive heart failure and cancer. In addition, eight novel SNPs were identified for associations with both ADRD and a comorbid condition.

Conclusions: Using a bivariate survival model approach, we identified genetic variants associated not only with ADRD, but also with comorbid conditions. Our utilization of dual-disease models represents a novel analytic strategy for uncovering shared genetic variants for multiple disease phenotypes.

Background: Apathy is a prevalent and debilitating neuropsychiatric symptom among persons living with Alzheimer's disease and related dementias, particularly those residing in long-term care facilities (LTCF). Despite its profound effects on the quality of life for both residents and their caregivers, apathy remains underrecognized and poorly understood in the context of dementia care.

Objective: To investigate the prevalence and biopsychosocial characteristics of apathy among newly admitted residents with dementia in Canadian LTCF using an Apathy Index derived from the interRAI Minimum Data Set (MDS) 2.0.

Methods: This cross-sectional study analyzed data from newly admitted residents with dementia from various LTCF (N = 97,789) across seven Canadian provinces between 2015 and 2019. Logistic regression analysis was performed to determine the relationship between apathy and multiple variables including sociodemographic and clinical variables. The biopsychosocial model of health was used to guide analysis.

Results: The prevalence rate of apathy among the Canadian long-term care residents with Alzheimer's disease and related dementias was 13.1%. Apathy was associated with various variables including male sex, pain, use of psychotropics, high Activity of Daily Living Self-Performance Hierarchy Scale scores, depression, aggression, severe cognitive impairment, and insomnia. Preferences for certain activities such as card games, art and craft, reading, music and exercise were inversely related to apathy while gardening was not.

Conclusions: By shedding light on this complex phenomenon within a Canadian context, we recommend that targeted interventions and improved care strategies to enhance the well-being of persons living with dementia should be prioritized in LTCF.

In recent years, the study of air pollution has received increasing attention from researchers, but a summary of Alzheimer's disease (AD) and air pollution is missed. Through combing the documents in the core dataset of Web of Science, this study analyzes current research based on specific keywords. CiteSpace and VOSviewer perform statistical analysis of measurement metrics to visualize a network of relevant content elements. The research devotes discussion to the relationship between air pollution and AD. Keyword hotspots include AD, children, oxidative stress, and system inflammation. Overall, 304 documents on air pollution and AD from 2013 to 2023 were retrieved from Web of Science. One hundred twenty-two journals published relevant articles, and the number of articles has increased gradually since the past decade. Research and development in AD and air pollution are progressing rapidly, but there is still a need for more connections with multidisciplinary technologies to explore cutting-edge hotspots.

Background: Evidence supports the neuroprotective effects of physical activity, either in experimental animal models or humans. However, the biological mechanisms by which physical exercise modulates dementia and Alzheimer's disease (AD) progression are still unclear.

Objective: This study investigated whether long-term (6 months) of voluntary wheel running induces neuroprotective effects in the pathogenesis of AD in middle-aged (8 months) female mice, focusing on energy metabolism.

Methods: A genetic mice model of AD (3xTg-AD) that performed wheel running presented changes in body metabolism and muscle oxidative profile, as well as restored discriminative and non-associative retention memories, evaluated by novel object recognition and open field tasks, respectively.

Results: In the hippocampus, these mice exhibited reduced levels of amyloidogenic AβPPβ fragment, phospho-Tau protein and phospho-Akt (activated form), without changes in phospho-AMPK (activated form). In addition, hippocampal mitochondria presented a restored respiratory function, characterized by lower coupling degree and weak contribution from complex I found in 3xTg-AD mice.

Conclusions: The results demonstrated that voluntary exercise improves cognitive parameters and biochemical hallmarks of AD, modulates Akt activation and enhances mitochondrial energy metabolism in hippocampus of middle-aged 3xTg-AD female mice, thereby reinforcing the neuroprotective role of physical exercise and the involvement of mitochondria in the etiology of the AD.

Background: Pre-existing dementia was related to poor functional outcome after intracerebral hemorrhage (ICH), and its commonly underlying pathologies were considered as cerebral amyloid angiopathy. But the impact of pre-existing dementia on in-hospital mortality in Chinese ICH patients has not been well characterized.

Objective: To investigate the association between pre-existing dementia and in-hospital mortality after ICH.

Methods: Data were extracted from the China Stroke Center Alliance database. Information about the existence of prior to stroke dementia was obtained from next of kin informants and registered in clinical charts. Patients' characteristics, in-hospital mortality, home discharge and complications were compared between ICH patients with and without pre-existing dementia.

Results: Out of the 72,318 ICH patients, we identified 328 patients with pre-existing dementia. Patients with pre-existing dementia were more likely to experience greater stroke severity as measured by the National Institute of Health Stroke Scale and Glasgow Coma Scale. In the adjusted models, the presence of pre-existing dementia was associated with an increased risk of in-hospital mortality (OR 2.31, 95% CI 1.12-4.77), more frequent in-hospital complications of pulmonary embolism (OR 5.41, 95% CI 1.16-25.14), pneumonia (OR 1.58, 95% CI 1.08-2.33), urinary tract infection (OR 2.37, 95% CI 1.21-4.64), gastrointestinal bleeding (OR 2.39, 95% CI 1.27-4.49) and lower home discharge (OR 0.59, 95% CI 0.38∼0.93).

Conclusions: ICH patients with pre-existing dementia are more likely to suffer from greater stroke severity, poorer outcomes and lower home discharge. Future studies should evaluate the value of intensive risk factor control among individuals with pre-existing dementia for stroke prevention.