Journal of Alzheimer's disease reports最新文献

Background: Deep cervical lymphovenous anastomosis (DLVA) shows promise for Alzheimer's disease (AD) treatment, but patient selection criteria remain undefined. Perivascular spaces (PVS) may predict glymphatic enhancement potential.

Objective: To investigate whether preoperative magnetic resonance imaging (MRI) measures of PVS burden can predict treatment response to DLVA in AD patients and explore potential mechanisms through longitudinal glymphatic function assessment.

Methods: Retrospective analysis of 10 AD patients undergoing DLVA. Preoperative T1-weighted MRI quantified PVS volumes using Frangi filtering. Treatment response was assessed at one month using Mini-Mental State Examination/Montreal Cognitive Assessment improvements ≥2 points.

Results: Total PVS volume demonstrated perfect predictive accuracy for treatment response (AUC = 1.000) with an optimal cut-off of 5150 mm³ (sensitivity 100%, specificity 100%). White matter PVS volume also showed strong predictive performance (AUC = 0.875, cut-off 3630 mm³, sensitivity 75%, specificity 100%). The improved group had significantly higher preoperative PVS volumes (total PVS: p = 0.012, Cohen's d = 2.631; white matter PVS: p = 0.050, Cohen's d = 1.689). Preliminary longitudinal analysis revealed divergent Analysis Along the Perivascular Space (ALPS) index changes: the improved group showed mean increase (+0.0276), while the non-improved group demonstrated decrease (-0.0252).

Conclusions: Preoperative PVS burden serves as a powerful predictor of DLVA response, with higher volumes indicating sufficient anatomical reserve for therapeutic benefit. These findings establish PVS volume as clinically actionable biomarkers for precision patient selection in glymphatic-targeted AD interventions.

Spinocerebellar ataxia type 8 (SCA8) is an autosomal dominant neurodegenerative disorder caused by CTG/CAG repeat expansion in ATXN8OS/ATXN8 genes. The primary clinical feature is cerebellar ataxia, but approximately 30% of patients present with cognitive impairment, characterized by attentional disturbances and executive dysfunction. These cognitive deficits remain poorly understood, and no functional neuroimaging studies have been reported. We report a case of SCA8 presenting predominantly with cognitive impairment and showing marked hypoperfusion in the posterior cingulate cortex (PCC) on N-isopropyl-p-[¹²³I]-iodoamphetamine single-photon emission computed tomography, closely resembling early-onset Alzheimer's disease. This case suggests PCC dysfunction may contribute to cognitive decline in SCA8.

Background: YouTube is increasingly used by patients and caregivers as a source of health information. However, the quality and reliability of content on Alzheimer's disease dementia (ADD) remain uncertain.

Objective: This study aimed to determine whether YouTube videos on ADD provide reliable and high-quality information for caregivers and to assess whether the most popular videos are also the most trustworthy.

Methods: In December 2024, YouTube was systematically searched for ADD-related videos. Two independent physicians reviewed each video, scoring it using modified DISCERN (mDISCERN) for reliability and the Global Quality Scale (GQS) for content quality. Videos were categorized by goal and assessed for quality, accuracy, comprehensiveness, and specific content.

Results: There were 117 videos included in the study. Using the mDISCERN scale, 70 videos (59.8%) were deemed with good reliability, 33 videos (28.2%) have moderate reliability, and 14 videos (12%) have poor reliability. Using the GQS, 61 videos (51.1%) have high quality, 16 videos (28%) were assessed as excellent quality, 34 videos (29%) as moderate quality, and 7 videos (6%) as low quality. Videos from academic institutions, news agency and physicians exhibited higher mDISCERN and GQS scores compared to other groups and a significant correlation was seen between mDISCERN and GQS (p < 0.001).

Conclusions: The videos on ADD produced by healthcare professionals and academic institutions have high quality and good reliability, covering disease properties, treatment choices, and patient experiences. However, video popularity does not significantly correlate with content reliability and quality.

Background: Neuroinflammation represents a central pathological mechanism in Alzheimer's disease (AD). Lipopolysaccharide (LPS) is a potent inducer of neuroinflammation and demonstrates elevated circulating levels in AD patients.

Objective: This study aims to investigate the genetic association between serum LPS activity level, inflammatory proteins and AD.

Methods: A two-sample mendelian randomization (MR) analysis was performed to explore the causal effect of serum LPS activity level and 91 inflammatory proteins on AD, including 1, 260, 136 sporadic AD and 2, 838, 825 familial AD patients, respectively. Meta-analysis was conducted on multiple datasets to determine statistically significant results that was initially observed in one dataset.

Results: Serum LPS activity level is a risk factor for early onset sporadic AD with OR = 1.392, 95% CI: 1.038-1.869. In most other sporadic AD datasets, LPS shows a trend of increasing the risk of AD onset. After meta-analysis in 10 independent datasets, no association between LPS and sporadic AD was observed. In most familial AD datasets, LPS level demonstrated a trend of decreasing AD risk in MR analysis, however, meta-analysis of the combined 8 datasets showed no statistically significant difference. Two inflammatory proteins, AXIN1 and IL-1 alpha, were identified as significant risk factors for sporadic AD.

Conclusions: This study suggested that serum LPS activity level may present a risk effect in early onset sporadic AD. Two inflammatory proteins AXIN1 and IL-1 alpha were associated with the risk of sporadic AD. These findings provide a new perspective for the early diagnosis and treatment of sporadic and familial AD.

Background: Deep cervical lymphaticovenular anastomosis (dcLVA) surgery is able to control aging-associated Alzheimer's disease in patients. However, the efficacy rate remains unknown.

Objective: This study is designed to test the surgery efficacy in the treatment of mild-to-moderate AD patients.

Methods: This is a single-center retrospective study of dcLVA treatment of mild-to-moderate AD for 3 months. A total of 41 patients received the surgery, in which lymph vessels and lymph nodes in the district III of cervical area were identified using indocyanine fluorescence dye. The afferent lymphatics of the obstructed lymph nodes were connected to the jugular vein to fix the lymphatic blockage under a fluorescent microscope. The efficacy rate was examined at 3-month post-surgery by clinical scores and biomarkers.

Results: Lymph flow obstruction was observed on both sides of cervical area in the AD patients. The obstruction was successfully resolved through the surgery, and AD progression was attenuated or even reversed in the patients according to improvement in the scales of MMSE, ADL, NPI, CDR-SB, and CGI-EI. The average effectiveness rate was 50% by the CDR-SB score improvement. The efficacy was higher with shorter disease duration but not influenced by age and APOE4 genotype. Aβ_42/40 ratio and p-tau181 were improved in more than 67% patients. There were 2 cases of mild adverse reactions that were controlled immediately by regular treatments.

Conclusions: The data demonstrate that dcLVA surgery is an effective and safe therapy for AD in mild-to-moderate patients with 50% efficacy rate as measured by improvement of the CDR-SB score.

Background: Evidence suggests statins may influence cognition in Alzheimer's disease (AD), but specific use patterns in AD patients remain unclear.

Objective: To identify factors influencing statin use in AD and explore associations between statins, cholesterol, and cognition, evaluated with Mini-Mental State Examination (MMSE) at dementia diagnosis.

Methods: A cross-sectional study using data from the Swedish Registry for Dementia and Cognitive Disorders (SveDem) and Stockholm Creatinine Measurements (SCREAM) from 2007 to 2018. Multivariable logistic regression examined associations between baseline characteristics and statin use, while linear regression analyzed relationships between statins, cholesterol levels, and MMSE scores.

Results: We included 3074 AD patients (mean age 78.1 years; 59.4% women), of whom 1028 used statins (79.6% simvastatin, 20.4% atorvastatin). Patients with diabetes mellitus, ischemic heart disease, or stroke had greater odds of receiving statins. Older patients had slightly lower odds of receiving any statin at baseline (simvastatin use OR 0.98, 95% CI 0.97-0.99). Simvastatin users had 0.53 points higher MMSE on average at baseline compared to non-users of statins (se 0.23, p = 0.021). Higher low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were associated with higher MMSE in non-users of statins, but not in statin users.

Conclusions: Younger AD patients and those with cardiovascular disease were more likely to use statins. Simvastatin use was linked to higher cognitive scores at diagnosis. In non-users, higher LDL-C, TC, and HDL-C levels correlated with better baseline cognitive scores. Longitudinal studies are needed to investigate the effects of statins on cognitive decline in AD.

Background: Alzheimer's disease (AD) is a neurodegenerative disease that causes a decline in cognitive functions, considerably affecting a patient's life. Recently, virtual reality (VR) technology has emerged as a new tool used in the cognitive training of patients with AD.

Objective: This study aimed to investigate the safety, feasibility, and clinical efficacy of VR-based cognitive training for patients with mild to moderate AD.

Methods: Thirteen participants diagnosed with mild to moderate AD underwent VR training sessions by using the MentiTree software. Each session was conducted for 30 min twice a week for 9 weeks (total of 540 min). Cognitive functions were assessed before and after the intervention.

Results: Although 1 of the 13 participants experienced adverse effects, the 9-week cognitive training was well tolerated and had a high feasibility of 93%±24.65%. A tendency toward improvement was observed in the visual recognition memory of the participants (p = 0.034), but other domains did not significantly change.

Conclusions: VR-based cognitive training is safely accepted by patients with mild to moderate AD. The potential of VR in AD treatment should be further explored using a randomized control group.

Background: Genome-wide studies have identified multiple risk genes for Alzheimer's disease (AD), yet the causal protein interactions and pathways driving AD pathogenesis remain unclear.

Objective: This study aimed to assess the causal relationships between plasma proteins and AD risk, and to delineate protein-mediated regulatory pathways involved in AD pathogenesis.

Methods: We assessed the causal relationships between plasma proteins and AD risk using protein quantitative trait loci (pQTL) data from two large-scale resources: the UK Biobank Pharma Proteomics Project (UKB-PPP) and deCODE genetics. These data were integrated with genome-wide association studies (GWAS) on AD. We applied two-sample Mendelian randomization (MR), followed by two-step MR and mediation analyses, to delineate causal regulatory pathways and quantify mediating effects of proteins in AD pathogenesis. To further provide supporting evidence, we analyzed transcriptomic data from postmortem AD brain tissues (GSE33000, Gene Expression Omnibus) and conducted differential expression analyses.

Results: In the UK Biobank cohort, seven upstream proteins showed causal associations with six downstream proteins in the deCODE cohort, which in turn influenced AD risk through both positive and negative regulatory effects (p < 0.05). Transcriptomic analysis demonstrated significant downregulation of KIAA0319 in AD patients (p < 0.0001). These findings were consistent with our mediation analysis, which indicated that reduced KIAA0319 expression adversely affected PMM2 and thereby increased AD risk (mediation effect: 13.37%, 95% CI: 1.68%-25.06%, p < 0.05).

Conclusions: This integrative analysis uncovered a novel KIAA0319-PMM2 regulatory axis implicated in AD pathogenesis. Both proteins represent potential therapeutic targets for future AD interventions.

Visual art therapy is an emerging non-pharmacological intervention that integrates mental health and human services to enhance cognitive functions. It has shown promising results in supporting cognitive performance among healthy elderly individuals, those with mild cognitive impairment (MCI), and individuals with mild to moderate dementia, particularly Alzheimer's disease (AD). Given the limitations of current pharmacological treatments for dementia, visual art therapy presents an accessible, engaging alternative that fosters cognitive, sensory, and emotional stimulation-potentially contributing to neuroplastic changes in the aging brain. Here, we review recent applications of visual art therapy for these populations, particularly focusing on AD. The review highlights the significant impact of visual art therapy on cognitive function, summarizing the main approaches used and exploring mechanisms of cognitive enhancement, which may involve alterations in brain structure, neuroplasticity, and the promotion of sensory system neuroplasticity, particularly in audition and vision. It also discusses enhancements in functional connectivity within the default mode network. Future research should investigate optimal art therapy methods, scientific evaluation and quantitative analysis, explore integration with other non-pharmacological interventions, and pursue interdisciplinary investigation of art therapy mechanisms through neuroimaging. This review offers new insights into the empirical evidence supporting the use of visual art therapy for improving cognitive function in both healthy elderly individuals and dementia patients, explores potential neurobiological mechanisms underlying its cognitive benefits, and identifies current gaps and future directions for interdisciplinary research and clinical application, thereby fostering further research and application to address cognitive decline.

Antibody-negative Autoimmune encephalitis (AE) presents a diagnostic challenge, requiring a high index of clinical suspicion and comprehensive evaluation. We report a 66-year-old man presenting with a seizure accompanied by progressive cognitive decline over several days. Despite the presence of hallmark symptoms and suggestive imaging, the patient was initially misdiagnosed, delaying timely immunotherapy. The diagnosis of antibody-negative AE was made based on clinical criteria, including consistent serological and cerebrospinal fluid (CSF) analyses (negative for known autoimmune and paraneoplastic antibodies), alongside a positive tissue-based assay (TBA), cranial MRI findings, and peripheral blood B-cell profiling. The patient responded well to immunotherapy with a low-dose sequential rituximab regimen, demonstrating clinical improvement and halting disease progression. This case highlights the importance of adhering to diagnostic criteria for AE and integrating TBA into the diagnostic workflow for antibody-negative AE.