Journal of Alzheimer's Disease最新文献

Amyloid-β peptide (Aβ), a hallmark peptide in the pathology of Alzheimer's disease, together with the amyloid-β protein precursor, is increasingly associated with the disruption of cell adhesion. In addition to its well-characterized role in plaque formation and synaptic dysfunction, Aβ interacts with various adhesion molecules and extracellular matrix components, thereby impairing neuronal connectivity and integrity. We have shown that pretreatment of SH-SY5Y cells with Aβ₄₂ fibrils affects cell adhesion; however, we did not observe this effect with Aβ₄₂ monomers. Understanding the molecular mechanisms by which Aβ fibrils disrupt cell adhesion pathways may reveal new therapeutic approaches to prevent disease progression.

BackgroundIncreasing evidence implicates herpes simplex virus type 1 (HSV1) in the pathogenesis of Alzheimer's disease (AD). The genome-wide association studies have not detected any genes regulating antibody responses to HSV1.ObjectiveTo determine whether the magnitude of antibody responses to HSV1 and to its glycoprotein D (gD) differed between AD patients and controls. Using a candidate gene approach, determine if the antibody responses were associated with immunoglobulin GM (γ marker) and KM (κ marker) allotypes-hereditary antigenic determinants of γ and κ chains, respectively. We also aimed to determine whether GM and KM allotypes epistatically interacted with an AD risk gene-reelin-encoding RELN (rs2299356)-and contributed to immunity to HSV1 and HSV1-gD.MethodsGenotyping was done by polymerase chain reaction-restriction fragment length polymorphism, TaqMan^®, and rhAMP^® SNP genotyping assays. IgG antibodies to HSV1 and HSV1-gD were measured by an enzyme-linked immunosorbent assay.ResultsAnti-HSV1 antibody levels were not significantly different between AD cases and controls; however, anti-HSV1-gD antibody levels were over two-fold higher (p < 0.0001) in AD cases compared to controls. GM 23 allele was associated with higher anti-HSV1 antibody levels in both cases and controls. Potential interaction between KM and RELN rs2299356 alleles on antibody responses to HSV1-gD was detected in AD cases, but not in controls.ConclusionsIn view of the fact that HSV1-gD is a vaccine candidate, the findings of higher anti-HSV1-gD antibody levels in AD patients and potential interaction of KM and RELN rs2299356 alleles in this study warrant additional large-scale multiethnic studies on this issue.

BackgroundHealth recommender systems show promise in delivering remote support and improving coping among family caregivers of persons with dementia.ObjectiveTo evaluate the effectiveness of a mobile-based intelligent recommender system for dementia care (DCIRS) in enhancing psychological well-being among family caregivers and to explore the mechanisms underlying its effects.MethodsData from a randomized controlled trial (RCT) were used. Of the 250 eligible participants, 125 caregivers were randomly allocated to the intervention group (receiving DCIRS) and 125 to the waitlist control group. Outcomes, including benefit finding, depressive symptoms, self-efficacy, and coping styles, were assessed at baseline (T0), 6 weeks (T1), and 12 weeks (T2). Generalized estimating equations (GEE) was used to evaluate changes over time and between-group differences, while path analysis examined mediation pathways.ResultsAt 12 weeks, the intervention group showed significant within-group improvements in coping, self-efficacy, and benefit finding (all p < 0.05 for group × time interaction). Between-group analyses revealed greater reductions in depressive symptoms at T1 and T2, though the group × time interaction was non-significant (p = 0.393). Path analysis indicated that reduced depressive symptoms were mediated primarily by increased self-efficacy.ConclusionsThis DCIRS demonstrated the potential to reduce depressive symptoms and enhance benefit finding in caregivers of people with dementia. Strengthening self-efficacy and active coping styles should remain a core focus in digital health interventions, providing meaningful guidance to healthcare professionals in developing caregiver support program.

BackgroundAgitation is a common behavioral and psychological symptom of dementia that places significant burden on caregivers. While its impact on family caregivers is well-documented, its effect on professional caregivers remains underexplored. Additionally, it is unclear whether existing caregiver burden scales adequately capture the International Psychogeriatric Association's (IPA) definition of agitation. Since agitation requires different treatment approaches than cognitive impairment, its distinct burden warrants further investigation.ObjectiveThis systematic review examined scales used to assess professional caregiver burden related to agitation in dementia.MethodsFollowing PRISMA guidelines, we searched MEDLINE, Embase, and ICHUSHI for English and Japanese articles published during January 1980-August 2024. Studies included professional caregivers, either exclusively or alongside informal caregivers. Key outcomes were the number and frequency of scales, target population, and agitation coverage within the scales.ResultsWe identified 52 articles: 22 focused exclusively on professional caregivers, and 30 included both types. Publications involving both caregiver types increased notably in the last decade. Across studies, 39 scales were used. The Zarit Burden Interview (n = 21) and Neuropsychiatric Inventory (n = 15) were most frequent. Sixteen scales targeted the general population; 11 each were designed for professional and informal caregivers, and one for both. Most scales did not fully reflect the IPA's definition of agitation. Scales for professional caregivers also included work-related factors like coworker conflicts and administrative workload.ConclusionsThere is a critical gap in validated scales to measure agitation-related burden in professional dementia caregivers. Specialized tools are urgently needed to assess this burden and guide support strategies.

BackgroundThere is a synergistic effect between sarcopenia and obesity, and they are important factors affecting cognitive function. It's essential to explore the complex relationship among the three.ObjectiveTo explore the mediating effect of waist circumference in the relationship between sarcopenia and cognitive function.MethodsA total of 5577 participants aged 60 years and older from CHARLS (China Health and Retirement Longitudinal Study) were included. Cognitive function was assessed via episodic memory and mental integrity. Sarcopenia status was diagnosed according to the criteria of the AWGS 2019. General linear regression models were applied to investigate the association between WC, sarcopenia, their combined effects and cognitive function. Mediation analysis was used to access the mediating effect of WC in the relationship between sarcopenia and cognitive function. The nonlinear association between WC and cognitive function was explored by using the restricted cubic spline model.ResultsAmong 5577 participants, the average cognitive score was 12.41. After controlling for confounding factors, participants with central obesity and severe sarcopenia had the worst cognitive scores (β = -3.22, 95%CI = -4.81, -1.61). WC mediated 16.95% of the association between sarcopenia and cognitive scores, and 9.26% of the association between severe sarcopenia and cognitive scores. The strongest positive association was found between WC and cognitive scores when WC was 96.74 cm in men.ConclusionsCentral obesity was associated with better cognitive function. However, central obesity accompanied by sarcopenia or severe sarcopenia was associated with lower cognitive function. There were significant differences in the mediating effect of WC between different sarcopenia status and cognitive function.

BackgroundDepression assessment in persons with dementia (PWD) often prioritizes caregiver report, with limited integration of self-report due to concerns about PWD insight.ObjectiveThis cross-sectional study examined discrepancies between self- and caregiver-reported depression in PWD and identified neuropsychiatric and diagnostic predictors of discordance.Methods402 PWD diagnosed with Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), or progressive supranuclear palsy (PSP) self-reported depression using the Geriatric Depression Scale (GDS), while caregivers completed the Neuropsychiatric Inventory (NPI). Discrepancies were categorized as Concordant (agreement), Discordant Type 1 (self-reported depression denied by caregiver), or Discordant Type 2 (caregiver-reported depression denied by PWD).ResultsOne-third (33.8%) of dyads showed discrepancies: 66.2% were concordant, 10.2% Discordant Type 1, and 23.6% Discordant Type 2. PSPs had higher incidence of Type 1 discordance compared to AD (OR = 2.91, p < 0.05), while svPPAs were less likely to incur Type 2 discordance than AD (OR = 0.33, p < 0.01). Higher self-reported GDS Hopelessness, Withdrawal, and Worry predicted higher rates of Type 1 discordance, while lower Dysphoria predicted Type 2 discordance. Higher caregiver-reported NPI Apathy increased odds of Type 1 discordance (OR = 2.46, p < 0.05) and lower NPI Anxiety increased odds of Type 2 discordance (OR = 0.50, p < 0.01). Among cases with Type 1 discordance, caregivers often endorsed PWD apathy, irritability, agitation, or anxiety instead of depression.ConclusionsDiscrepancies in reporting depression in PWD can reflect underreporting by caregivers, not only denial by PWD. Integrating self-report, caregiver input, and clinical judgment may improve diagnostic accuracy for depression in PWD and improve care.

BackgroundConsidering the multidimensional nature of self-report sleep health may improve identification of those at risk of accelerated cognitive decline and dementia.ObjectiveWe compared how composite measures of multidimensional sleep health relate to cognitive performance and the risk of dementia over time in older adults.MethodsSelf-reported indicators of sleep health domains (satisfaction, alertness, timing, efficiency, and duration) were measured in 7892 Rotterdam Study (RS) participants (mean ± SD age: 69.5 ± 8.9 years, 58.2% female) and 1601 Rush Memory and Aging Project and Minority Aging Research Project (MAP/MARS) participants (79.5 ± 7.9 years, 77.3% female). Sleep items were harmonized and used to derive a sleep health score (number of adverse sleep health items) and sleep health clusters (with latent class analysis). During follow-up, multiple cognitive tests were performed repeatedly and participants were followed for incident all-cause dementia. Relationships of sleep health with cognitive decline (linear mixed models) and risk of dementia (Cox proportional hazards models) were assessed in both samples, adjusting for covariates.ResultsThree sleep health clusters were identified: average sleep, inefficient sleep, and poor sleep. During follow-up of 10.6 ± 4.5 years in RS and 5.3 ± 2.9 years in MAP/MARS, 1148 (14.5%) and 286 (19.8%) participants developed dementia, respectively. Multidimensional sleep health scores and clusters were not significantly associated with accelerated cognitive decline or the risk of dementia in either sample (Hazard Ratios [HRs] between 0.72-1.15).ConclusionsFindings suggest composite measures of self-reported multidimensional sleep health need refinement to be useful in identifying older adults at risk of accelerated cognitive decline and dementia.

BackgroundVascular factors contribute to dementia in approximately 20 million individuals, notably in vascular contributions to cognitive impairment and dementia (VCI). However, the lack of specific molecular biomarkers to differentiate VCI from normal aging and Alzheimer's disease (AD) impedes early diagnosis and treatment.ObjectiveTo date the use of saliva for VCI diagnosis has not been previously reported. In this small proof-of-concept study, we aim to explore the feasibility of screening novel salivary diagnostic biomarkers for VCI.MethodsUsing both proton nuclear magnetic resonance (¹H NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS) we biochemically profiled saliva samples collected from individuals with VCI (n = 26) and compared them with cognitively healthy controls (n = 37).ResultsOf the 167 salivary metabolites 56 of them are found to be at significantly different concentrations in the saliva of individuals with VCI as compared to controls. Subsequently, we developed predictive models capable of distinguishing VCI from controls with 0.92 accuracy. Moreover, sex-stratified analysis revealed the perturbation of different metabolic pathways in the saliva of individuals with VCI.ConclusionsThis study underscores the promising role of salivary metabolomics as a non-invasive tool for the early detection of VCI. Our findings suggest that oral microbiome dysbiosis may contribute to VCI pathogenesis, offering novel mechanistic insights. Given the accessibility of saliva, further validation of these robust salivary biomarkers could facilitate scalable, cost-effective screening for VCI, aiding in timely intervention strategies.

BackgroundGrowing evidence links periodontitis to Alzheimer's disease (AD), yet the specific links between periodontitis severity gradients and brain functional alterations remain poorly understood.ObjectiveTo investigate brain functional alterations quantified by functional connectivity density (FCD) and regional homogeneity (ReHo) across periodontitis severity gradients, include microbiota measures as explanatory variables, and assess correlations between these functional alterations and cognitive impairment.MethodsClinical periodontal data, subgingival plaque, cognitive tests, and brain MRI data were collected from all 89 participants, including community-recruited normal cognition (NC) and patients with amnestic mild cognitive impairment (aMCI) and AD from a hospital neurology department. According to periodontal examination, participants were categorized into mild, moderate, and severe groups. FCD and ReHo were compared among different periodontal condition groups and subgroups. Correlation analyses were conducted to explore the relationship among FCD, ReHo, periodontal indices, and cognition.ResultsWith increasing severity of periodontitis, the FCD of bilateral middle frontal gyrus (MFG.R, MFG.L), right inferior frontal gyrus, triangular part (IFGtriang.R), and the ReHo of IFGtriang.R all decreased. These regions are commonly associated with executive control, working memory, and attention. These changes were more strongly correlated with overall periodontal inflammatory burden and cognitive performance than to the abundance of specific taxa in the subgingival plaque microbiota.ConclusionsPeriodontitis severity is associated with reduced prefrontal FCD/ReHo and cognitive decline, and these associations appear to be more strongly driven by overall periodontal inflammatory burden than by specific subgingival taxa.

BackgroundWoohwangchungsimwon (WCW) is a traditional Korean herbal formula commonly used to treat anxiety and restlessness. However, its potential role in managing behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) is unclear.ObjectiveThis study evaluated the efficacy and safety of WCW as an adjunctive treatment for BPSD in patients with mild probable AD already receiving donepezil.MethodsSeventy-four patients receiving donepezil 5 mg daily were randomized 1:1 into an intervention group (WCW add-on, n = 37) or a control group (no additional treatment, n = 37) for 24 weeks. The primary outcome was the change in BPSD measured using the Neuropsychiatric Inventory (NPI). Secondary outcomes were cognitive function and emotional and physical well-being, including depression, anxiety, insomnia, quality of life, and severity of dementia. Safety was assessed via adverse events and laboratory results.ResultsSixty-three participants were included. The WCW group demonstrated significantly improved total NPI scores versus controls, particularly in the irritability/lability subdomain. Analysis of covariance (ANCOVA) confirmed these findings in both the full analysis set (FAS) and per-protocol set (PPS). T-test and rank ANCOVA showed significance in the PPS and a trend in the FAS. The general quality of life dementia scale showed a trend toward improvement. No significant differences in adverse events or laboratory results were observed.ConclusionsWCW may be a safe and effective adjunctive therapy for BPSD in patients with mild probable AD. Future studies should adopt more rigorous designs and include patients with broader disease severity to enhance clinical applicability.Trial registrationThe trial was registered with the Clinical Research Information Service (CRIS) on December 10, 2020 (KCT0005669).