Journal of Alzheimer's disease reports最新文献

Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer's disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder linked to the loss of dopaminergic neurons in the substantia nigra. Mitophagy, mitochondrial selective autophagy, is critical in maintaining mitochondrial and subsequently neuronal homeostasis. Its impairment is strongly implicated in PD and is associated with accelerated neurodegeneration.

Objective: To study the positive effect of dimethyl fumarate (DMF) on mitophagy via the NRF2/BNIP3/PINK1 axis activation in PD disease models.

Methods: The neuroprotective effect of DMF was explored in in vitro and in vivo PD models. MTT assay was performed to determine the DMF dose followed by JC-1 assay to study its mitoprotective effect in MPP⁺ exposed SHSY5Y cells. For the in vivo study, C57BL/6 mice were divided into six groups: Normal Control (NC), Disease Control (DC), Sham (Saline i.c.v.), Low Dose (MPP⁺ iodide+DMF 15 mg/kg), Mid Dose (MPP⁺ iodide+DMF 30 mg/kg), and High Dose (MPP⁺ iodide+DMF 60 mg/kg). The neuroprotective effect of DMF was assessed by performing rotarod, open field test, and pole test, and biochemical parameter analysis using immunofluorescence, western blot, and RT-PCR.

Results: DMF treatment significantly alleviated the loss of TH positive dopaminergic neurons and enhanced mitophagy by increasing PINK1, Parkin, BNIP3, and LC3 levels in the MPP⁺ iodide-induced PD mice model. DMF treatment groups showed good locomotor activity and rearing time when compared to the DC group.

Conclusions: DMF confers neuroprotection by activating the BNIP3/PINK1/Parkin pathway, enhancing the autophagosome formation via LC3, and improving mitophagy in PD models, and could be a potential therapeutic option in PD.

Background: Composite scores have been increasingly used in trials for Alzheimer's disease (AD) to detect disease progression, such as the AD Composite Score (ADCOMS) in the lecanemab trial.

Objective: To develop a new composite score to improve the prediction of outcome change.

Methods: We proposed to develop a new composite score based on the statistical model in the ADCOMS, by removing duplicated sub-scales and adding the model selection in the partial least squares (PLS) regression.

Results: The new AD composite Score with variable Selection (ADSS) includes 7 cognitive sub-scales. ADSS can increase the sensitivity to detect disease progression as compared to the existing total scores, which leads to smaller sample sizes using the ADSS in trial designs.

Conclusions: ADSS can be utilized in AD trials to improve the success rate of drug development with a high sensitivity to detect disease progression in early stages.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with cognitive decline and behavioral dysfunction. AD will become a global public health concern due to its increasing prevalence brought on by the severity of global aging. It is critical to understand the pathogenic mechanisms of AD and investigate or pursue a viable therapy strategy in clinic. Amyloid-β (Aβ) accumulation and abnormally hyperphosphorylated tau protein are the main regulating variables in the pathological phase of AD. And neuroinflammation brought on by activated microglia was found to be one risk factor contributing to changes in Aβ and tau pathology. It is important to investigate the unique biomarkers of early diagnosis and advanced stage, which may help to elucidate the specific pathological process of AD and provide potential novel therapeutic targets or preventative measures.

Background: Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. However, findings comparing SCC and objective cognitive performance have varied, particularly in the memory domain. Even less well established is the relationship between subjective and objective complaints in non-amnestic domains, such as in executive functioning, despite evidence indicating very early changes in these domains. Moreover, particularly early changes in both amnestic and non-amnestic domains are apparent in those carrying the Apolipoprotein-E ɛ4 allele, a primary genetic risk for Alzheimer's disease (AD).

Objective: This study investigated the role of the ɛ4 allele in the consistency between subjective and objective executive functioning in 54 healthy, cognitively intact, middle-aged and older adults.

Methods: Participants (M_age = 64.07, SD = 9.27, range = 48-84; ɛ4+ = 18) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure subjective executive functioning (SEF) and multiple executive functioning tasks, which were condensed into a single factor.

Results: After accounting for age, depression, and anxiety, objective executive functioning performance significantly predicted SEF. Importantly, ɛ4 moderated this effect. Specifically, those carrying the ɛ4 allele had significantly less accurate self-awareness of their executive functioning compared to ɛ4 non-carriers.

Conclusions: Utilizing an approach that integrates self-evaluation of executive functioning with objective neurocognitive assessment may help identify the earliest signs of impending cognitive decline, particularly in those with genetic risk for AD. Such an approach could sensitively determine those most prone to future cognitive decline prior to symptom onset, when interventions could be most effective.

Background: Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia.

Objective: To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments.

Methods: Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected.

Results: Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. APOE4 may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression.

Conclusions: Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. APOE4 predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.

Background: Alzheimer's disease (AD) is one of the most debilitating diseases in old age, associated with cognitive decline and behavioral symptoms.

Objective: This study aimed to investigate the effect of adding mirtazapine to quetiapine in reducing agitation among patients with AD.

Methods: Thirty-seven elderly patients (18 cases and 19 controls) with AD, diagnosed according to National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, were enrolled at Nezam-Mafi Clinic. Inclusion criteria comprised a minimum of two years post-diagnosis, a Cohen-Mansfield Agitation and Aggression Questionnaire (CMAI) score above 45, and treatment with 100-150 mg of quetiapine. Patients were randomly assigned to receive mirtazapine (15 mg at night, increased to 30 mg at night after two weeks) or a placebo. Cognitive changes were assessed at weeks 0 and 6 using the Mini-Mental State Examination instrument. Furthermore, symptoms of agitation and aggression were evaluated using the CMAI questionnaire at weeks 4 and 6.

Results: In this study, the mean duration of AD in the control group was 4.68 years, and in the case group, it was 5.05 years. Although the total agitation score showed no significant change at the end of the study compared to the control group, the rate of physical non-aggressive behavior showed a significant decrease (p <  0.05).

Conclusions: According to this study, adding mirtazapine to the antipsychotic drug regimen may not be an effective treatment for agitation in AD patients.

Background: The investigation of mitophagy in Alzheimer's disease (AD) remains relatively underexplored in bibliometric analysis.

Objective: To delve into the progress of mitophagy, offering a comprehensive overview of research trends and frontiers for researchers.

Methods: Basic bibliometric information, targets, and target-drug-clinical trial-disease extracted from publications identified in the Web of Science Core Collection from 2007 to 2022 were assessed using bibliometric software.

Results: The study encompassed 5,146 publications, displaying a consistent 16-year upward trajectory. The United States emerged as the foremost contributor in publications, with the Journal of Alzheimer's Disease being the most prolific journal. P. Hemachandra Reddy, George Perry, and Xiongwei Zhu are the top 3 most prolific authors. PINK1 and Parkin exhibited an upward trend in the last 6 years. Keywords (e.g., insulin, aging, epilepsy, tauopathy, and mitochondrial quality control) have recently emerged as focal points of interest within the past 3 years. "Mitochondrial dysfunction" is among the top terms in disease clustering. The top 10 drugs/molecules (e.g., curcumin, insulin, and melatonin) were summarized, accompanied by their clinical trials and related targets.

Conclusions: This study presents a comprehensive overview of the mitophagy research landscape in AD over the past 16 years, underscoring mitophagy as an emerging molecular mechanism and a crucial focal point for potential drug in AD. This study pioneers the inclusion of targets and their correlations with drugs, clinical trials, and diseases in bibliometric analysis, providing valuable insights and inspiration for scholars and readers of JADR interested in understanding the potential mechanisms and clinical trials in AD.

Background: Alzheimer's disease (AD) is a genetically intricate neurodegenerative disorder. Studies on "Ferroptosis in AD", "Pyroptosis in AD", and "Necroptosis in AD" are becoming more prevalent and there is increasing evidence that they are closely related to AD. However, there has not yet been a thorough bibliometrics-based investigation on this subject.

Objective: This study uses a bibliometric approach to visualize and analyze the literature within the field of three distinct types of cell death in AD and explores the current research hotspots and prospective research directions.

Methods: We collected relevant articles from the Web of Science and used CiteSpace, VOS viewer, and Pajek to perform a visual analysis.

Results: A total of 123, 95, and 84 articles were published in "Ferroptosis in AD", "Pyroptosis in AD", and "Necroptosis in AD", respectively. Based on keywords analysis, we can observe that "oxidative stress" and "lipid peroxidation", "cell death" and "activation", and "Nlrp3 inflammasome" and "activation" were the three most prominent words in the field of "Ferroptosis in AD", "Pyroptosis in AD", and "Necroptosis in AD", respectively. Focusing on the breakout words in the keyword analysis, we reviewed the mechanisms of ferroptosis, pyroptosis, and necroptosis in AD. By mapping the time zones of the keywords, we speculated on the evolutionary trends of ferroptosis, pyrotosis, and necroptosis in AD.

Conclusions: Our findings can help researchers grasp the research status of three types of cell death in AD and determine new directions for future research as soon as possible.

Background: Future thinking and prospective memory are two cognitive processes oriented toward the future and reliant on the ability to envision oneself in future scenarios.

Objective: We explored the connection between future thinking and prospective memory in individuals with Alzheimer's disease (AD).

Methods: We invited both AD participants and control participants to engage in event-based prospective memory tasks (e.g., "please hand me this stopwatch when I inform you there are 10 minutes remaining") and time-based prospective memory tasks (e.g., "close the book you are working on in five minutes"). Additionally, we asked participants to engage in a future thinking task where they imagined upcoming events.

Results: Analysis revealed that AD participants exhibited lower performance in both prospective memory tasks and future thinking compared to the control group. Importantly, we identified significant positive correlations between the performance on event- and time-based prospective memory tasks and future thinking abilities among AD participants.

Conclusions: These findings underscore the connection between the decline in both prospective memory domains and the ability to envision future events in individuals with AD. Our results also shed light on the challenges AD individuals face when trying to project themselves into the future to mentally pre-experience upcoming events.