搜索结果：Alzheimer's & dementia : the journal of the Alzheimer's Association

B-cell depleting therapies (BCDT), including ocrelizumab, ofatumumab, and ublituximab, are highly effective disease-modifying therapies for multiple sclerosis (MS). Several case reports have raised concerns about new-onset or exacerbation of psoriasis under BCDT. This article aims to analyze clinical characteristics, treatment courses, and outcomes of MS patients who developed or experienced worsening of psoriasis during BCDT. This retrospective, multicenter analysis included patients from four German university hospitals (Düsseldorf, Hannover, Bochum, Giessen). We retrospectively screened 3228 MS patients under BCDT between 2020 and 2024 for development of psoriasis or an exacerbation of a known psoriasis. Clinical data, including Expanded Disability Status Scale, Psoriasis Area and Severity Index scores, treatment regimens, and comorbidities, were analyzed. Among 3228 patients treated with BCDT, 7 developed new-onset psoriasis and 10 showed exacerbation of preexisting psoriasis. The median time to psoriasis onset or worsening was 13 months (3-83 months) under continuous treatment with BCDT. Topical therapies were effective in most cases, but a change of MS treatment or initiation of psoriasis-specific immunotherapies, including the interleukin-17A-antibody secukinumab, was required in four patients. Psoriasis onset or worsening during BCDT is rare. While most cases are manageable with standard psoriasis treatments, severe cases may necessitate therapy adjustments. The potential immunological interplay between MS and psoriasis treatment warrants further investigation. Psoriasis in people with multiple sclerosis treated with B-cell therapies: an analysis from several medical centres Why was this study done? Multiple sclerosis (MS) causes inflammation of the brain and spinal chord as well as a slowly progressing loss of function in daily life. Medicines called B-cell therapies are very effective in treating MS. However, there have been reports that some people develop the skin condition psoriasis, or see their psoriasis get worse, while on these treatments. We wanted to find out how often this happens, what it looks like in patients, and how it can be managed. What did the researchers do? We looked back at the medical records of 3,228 people with MS who received B-cell therapy at four German hospitals between 2020 and 2024. We checked how many of them developed psoriasis for the first time or had their existing psoriasis get worse. We also collected information on the severity of psoriasis and MS as well as the treatments used. What did the researchers find? Seventeen people developed psoriasis problems while on B-cell therapy. Seven patients developed psoriasis for the first time, and ten had worsening of psoriasis they already had. On average, this happened about one year after starting treatment. In most patients, standard creams and ointments worked well. In a few cases, however, doctors had to change the MS treatment or add a psoriasis-specific medicine. What do these results mean? Psoriasis during B-cell therapy is uncommon. When it happens, it can often be treated with regular skin treatments, but sometimes stronger medicines or treatment changes are needed. More research is needed to understand why this happens and how MS and psoriasis treatments may affect each other.

Postoperative delirium is the most common postoperative complication in older individuals. Genome-wide association studies (GWAS) can provide insights into how genetic factors influence postoperative risk. We examined the genetic architecture of postoperative delirium after major surgery and its relationship with related cognitive conditions (delirium of any type and Alzheimer's disease, including the APOE &#x3b5;4 allele). A case-control GWAS was performed in the UK Biobank to identify genetic variants associated with postoperative delirium, adjusted for age, sex, genetic chip, and the first 10 principal components. These results were then used in genetic correlation and polygenic risk score analyses to investigate shared genetic risk between postoperative delirium and a) delirium of all causes, and b) Alzheimer's disease. The GWAS (1,016 cases, 139,148 controls) identified seven Single Nucleotide Polymorphisms (SNPs) that mapped to four genes (APOE, TOMM40, APOC1, and PVRL2); p&#x2009;<&#x2009;5 x 10-8. Five SNPs remained significant after excluding pre-existing dementia, and two after excluding subsequent dementia. The lead SNP was rs429358, a missense variant of APOE. Genetic correlation and polygenic risk score analyses revealed evidence of shared genetic architecture and risk between postoperative delirium and Alzheimer's disease (rho 0.68, 95% CI [0.46, 0.81]; p&#x2009;<&#x2009;0.001). After adjustment for age and sex, the APOE &#x3b5;4 isoform had a dose-response effect on risk (odds ratios for one and two copies: 1.75, 95% CI [1.53, 2.0], and 4.19, 95% CI [3.25, 5.41], respectively; p&#x2009;<&#x2009;0.001). The main limitations of the study include the reliance upon clinical coding for outcome definition and limited statistical power to detect small or modest genetic effects. We identified genetic variants associated with increased risk of postoperative delirium. We also found evidence of shared genetic liability with Alzheimer's disease via APOE, complementing recent large-scale studies in all-cause delirium. If validated, the findings have potential clinical applications, including preoperative risk stratification and early identification of pre-clinical Alzheimer's disease risk.

Alcohol consumption is an increasingly recognised modifiable risk factor for dementia, yet whether it has differential impacts on dementia subtypes and its role in disease progression remains unclear. This study aims to: (1) quantify the association between alcohol intake and incidence of dementia subtypes and (2) examine whether individuals who drink heavily and develop dementia referred to hereafter as 'alcohol-related'-have poorer post-diagnosis outcomes compared with other dementia cases. Clarifying these relationships will determine whether alcohol selectively increases risk for specific dementia phenotypes or broadly heightens neurodegenerative vulnerability, with implications for prevention, clinical counselling and therapeutic targeting. This population-based cohort study of alcohol and dementia will use linked UK electronic health records from Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics (ONS). Participants will be eligible if they have available linked data from January 1998, when ONS death registrations became available, until the end of follow-up. Alcohol exposure will be defined through self-reported recorded weekly alcohol units and diagnostic codes for harmful or dependent alcohol use. Primary outcomes including incident all-cause and subtype-specific dementia (eg, Alzheimer's, vascular, Lewy body, Parkinson's, frontotemporal) as well as secondary outcomes (ie, mortality, care-home entry and neuropsychiatric symptoms). Key covariates encompassing socio-demographic factors, smoking and relevant comorbidities will be adjusted for. Multivariable Cox proportional hazards and Fine-Gray competing risk models will estimate associations with dementia incidence. Post-diagnosis prognosis will be compared for dementia in individuals with a history of heavy alcohol use ('alcohol-related') and dementia in individuals with minimal alcohol exposure ('non-alcohol-related') cases using survival and logistic regression models. Multiple testing correction will be applied across dementia subtype comparisons. Alcohol exposure will be modelled continuously and non-linearly using restricted cubic splines and categorically using binary indicators of harmful/dependent use. Missing covariate data will be assessed and addressed using appropriate methods, including multiple imputation and complete-case analysis. Data extraction and analysis are scheduled from October 2025 to October 2026. Use of de-identified routine data will proceed under existing Research Ethics Committee and data governance approvals. Findings will be disseminated via open-access peer-reviewed journals, academic conferences and summaries targeted at patient, public and policy audiences. The results of this study will be reported according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) guidelines.

This study aimed to conduct a comprehensive bibliometric analysis to identify global research trends, key contributors and emerging hot spots in the field investigating the association between periodontitis and Alzheimer's disease (AD). Scientific publications from 2002 to 2025 were retrieved from the Web of Science Core Collection (WoSCC) and Scopus databases. The data were analysed using VOSviewer, CiteSpace and the R package 'bibliometrix' to perform co-authorship, co-occurrence and citation analyses. A total of 262 articles from WoSCC and 272 from Scopus were included in the analysis. China was the leading contributing country, and Shanghai Jiao Tong University was the most productive institution. The Journal of Alzheimer's Disease was identified as the most influential journal in this domain. Keyword co-occurrence analysis identified central research themes, including 'dementia', 'tooth loss', and 'Porphyromonas gingivalis'. Citation burst analysis indicated that 'oral microbiome' and 'oral health' are currently emerging research frontiers. This is the first bibliometric study to systematically map the intellectual structure and evolution of research linking periodontitis and AD. The findings underscore the strengthening link between oral inflammatory conditions and neurodegeneration. The analysis highlights a shifting focus towards mechanisms such as the oral microbiome and systemic inflammation, pointing to promising directions for future research aimed at novel preventive strategies and therapeutic interventions for AD.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). In CTE, hyperphosphorylated tau (p-tau) aggregates are found in neurons at the depth of cortical sulci close to the gray matter/white matter (GM/WM) boundary. To date, CTE can only be diagnosed postmortem by neuropathological examination. Traumatic encephalopathy syndrome (TES) is the clinical syndrome purported to be associated with CTE pathology. The aim of this study is to investigate microstructural properties at the GM/WM boundary in individuals with a history of exposure to RHI and clinical features of CTE (i.e., TES). Diffusion magnetic resonance imaging (dMRI), TES diagnoses, and cerebrospinal fluid (CSF) biomarkers were acquired from 165 male former American football players (age: 57.29 &#xb1; 8.23 years) from the DIAGNOSE CTE Research Project, a multicenter, observational cohort study. Fractional anisotropy (FA) was measured at the GM/WM boundary of the whole brain. In addition, a widely used method (tract-based spatial statistics [TBSS]) was applied to measure FA of central WM. We used analyses of covariance to test associations between FA and TES. Furthermore, we used linear regressions to test associations between FA and nine CSF biomarkers (i.e., p-tau-181, -217, -231, total tau, amyloid &#x3b2; [A&#x3b2;]1-40, A&#x3b2;1-42, glial fibrillary acidic protein [GFAP], neurofilament light [NfL], and soluble triggering receptor expressed on myeloid cells-2 [sTREM2]). We report an association between higher FA at the GM/WM boundary and higher levels of certainty for CTE pathology (F(1, 147) = 5.781, 95% confidence interval (CI) = 0.0003-0.003, p = 0.035) as well as neurobehavioral dysregulation (F(1, 148) = 7.559, 95% CI = 0.001-0.009, p = 0.020), and functional dependence/dementia (F(1, 148) = 5.046, 95% CI = 0.0004-0.006, p = 0.039). In addition, we report an association between higher FA at the GM/WM boundary and higher CSF p-tau-181 (&#x3b2; = 0.272, 95% CI = 0.078-0.466, p = 0.029) and p-tau-217 (&#x3b2; = 0.295, 95% CI = 0.102-0.488, p = 0.027). FA of the central WM was not associated with TES diagnoses. Taken together, these findings suggest that dMRI at the GM/WM boundary could be used to investigate microstructural alterations suggestive of tau pathology-associated neurodegeneration in individuals with TES, the clinical presentation of CTE. Future studies are needed to validate this approach and to identify clinically useful cutoff values for dMRI metrics.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and behavioral deterioration. In recent years, the role of the insulin-like growth factor-1 (IGF-1) signaling pathway in the pathological process of AD has received increasing attention. This study provides a visual analysis of the current research status, development trends, collaboration networks, and research hotspots related to IGF-1 and AD. Publications were retrieved from the Web of Science and Scopus databases. CiteSpace, VOSviewer, and Bibliometrix software were used for visual analysis. A total of 632 publications were included in the study. The annual publications related to IGF-1 and AD exhibited an overall upward trend. Research was concentrated in North America, Asia, and Europe. The United States holds a dominant position in terms of output, influence, and international influence. The Consejo Superior de Investigaciones Cient&#xed;ficas was the most active institution. Journal of Alzheimer's Disease was the journal with the highest number of publications. Dr. Ignacio Torres-Aleman was the most prolific author. High-frequency keywords included IGF-1, AD, brain, insulin, controlled study, metabolism, oxidative stress, animals, signal transduction, amyloid beta protein, dementia, aging, and neuroprotection. Transgenic mouse, risk, depression, and cognitive impairment were the most powerful keywords that have emerged in recent years. Research on IGF-1 and AD has continued to grow. Studies in this field have formed a tightly interconnected network, centered on the AD pathological core-IGF-1-related molecular mechanisms-downstream signaling pathways. The research focus is shifting from superficial correlations to investigations into underlying mechanisms and potential therapeutic targets. Depression and cognitive impairment are likely to become promising frontiers for future research.

Butyrylcholinesterase (BChE), once regarded as a redundant cholinesterase, has emerged as an important modulator of Alzheimer's disease (AD). Unlike acetylcholinesterase (AChE), which declines during disease progression, BChE activity is preserved or elevated in the AD brain and becomes the predominant cholinesterase in advanced stages. Beyond its enzymatic role in acetylcholine hydrolysis, BChE is directly associated with amyloid plaques and tau pathology and has been implicated in neuroinflammatory processes. Genetic variants of the BCHE gene, most notably the K-variant, further contribute to inter-individual differences in AD susceptibility, disease onset, and therapeutic response, particularly in the context of APOE4. Evidence from biochemical, histological, and clinical studies indicates that BChE influences both the pathophysiology of AD and the effectiveness of cholinesterase inhibitor therapy, with rivastigmine providing unique benefits through dual AChE and BChE inhibition. Recent efforts to develop selective or multitarget BChE inhibitors underscore the enzyme's potential as a therapeutic target, while BChE-specific positron emission tomography tracers highlight its diagnostic promise by distinguishing AD-related amyloid plaques from those of normal aging. Despite these advances, uncertainties remain regarding the precise dynamics of BChE activity across disease stages, its contribution to plaque maturation and inflammation, and its influence on responses to novel anti-amyloid antibody therapies. Overall, BChE represents a multifaceted factor in AD pathogenesis, therapy, and biomarker development, warranting further genotype-stratified and mechanistic investigations to clarify its clinical utility.

Previous findings on the link between metabolic syndrome (MetS) and the risk of all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), and cognitive decline are inconsistent. We systematically searched Embase, PubMed, Web of Science, the Cochrane Library, and Scopus up to June 2025 for prospective cohort studies conducted in community-based settings among adults aged 18&#xa0;years or older that reported risk estimates (e.g., relative risks, hazard ratios, or odds ratios) for the association between MetS and the risk of dementia or cognitive decline. Risk of bias for studies were assessed using ROBINS-I, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was applied to evaluate the certainty of evidence. Relative risks (RR) with 95%CI were computed using a random-effects inverse-variance method. Twenty-eight cohorts involving 6,753,197 participants were examined. MetS was significantly associated with a higher risk of all-cause dementia (RR&#x2009;=&#x2009;1.11, 95%CI: 1.07-1.14; absolute risk difference: 2 more cases per 1000 persons), VD (RR&#x2009;=&#x2009;1.33, 95%CI: 1.21-1.46; absolute risk difference: 7 more per 1000), and cognitive decline (RR&#x2009;=&#x2009;1.24, 95%CI: 1.10-1.40; absolute risk difference: 5 more per 1000), all based on low-certainty evidence. No significant association was found between MetS and AD, with very low certainty. MetS components of hypertension, hyperglycemia, and low HDL-C were key risk factors, with a dose-response relationship observed between the number of MetS components and dementia risk. Subgroup analyses indicated MetS increased all-cause dementia risk in individuals under 70 (p-value for interaction: 0.048). MetS was positively associated with increased risk of all-cause-dementia, VD, and cognitive decline, but not AD. However, the effect sizes were modest and the certainty of evidence was low. Further prospective cohort studies are needed to confirm the associations.

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are two of the most common neurodegenerative diseases in older adults, and both show well-documented sex-specific differences in terms of clinical presentation, prevalence, and progression trajectories. However, the underlying neurobiological substrates that underpin these differences are poorly understood. In vivo biomarkers are well-suited to yield insights into how biological sex may shape disease pathophysiology in AD and DLB, and thus inform future research and precision medicine. The objective of this review is to synthesize recent evidence on sex differences related to biomarkers of AD and DLB. We conducted a literature search of PubMed for studies published between January 2000 and May 2025 examining sex differences in neuroimaging and biofluid markers of mild cognitive impairment (MCI), AD, and/or DLB. Eligible studies were required to include sex-stratified or sex-interaction analyses in human participants with clinically defined MCI (due to AD or DLB), AD, or DLB. Of a total of 261 articles imported for screening, 63 met inclusion criteria, comprising 50 cross-sectional and 13 longitudinal investigations across biofluid markers (n&#x202f;=&#x202f;18) studies, structural imaging (n&#x202f;=&#x202f;18), functional imaging (n&#x202f;=&#x202f;16), and molecular imaging (n&#x202f;=&#x202f;11) studies. Women demonstrated initial cortical structural and metabolic advantages followed by accelerated decline. In MCI and AD, women were generally more susceptible to tau pathology and APOE &#x3b5;4-related risk. In contrast, men with DLB showed greater metabolic and dopaminergic abnormalities, though women with DLB frequently exhibited mixed biomarker profiles. APOE &#x3b5;4 conferred increased vulnerability in women for both conditions. Biofluid markers also revealed sex-specific expression patterns and associations with clinical outcomes. There is growing evidence that biological sex significantly influences the pathophysiology of AD and DLB as captured by in vivo biomarkers. These findings highlight the growing importance of analyses that consider sex differences in biomarker research and support the development of personalized diagnostic and therapeutic strategies in neurodegeneration. Future research should prioritize longitudinal studies to define optimal biomarker sequencing and therapeutic windows for each sex, while also investigating the genetic, hormonal, metabolic, pharmacological, and environmental mechanisms that underlie these sex differences, ultimately advancing precision medicine in neurodegenerative disease.

Walking the Talk for Dementia (WTD) is a global educational initiative integrating a walk along the Camino de Santiago with a symposium to combat dementia stigma, raise awareness, and foster inclusion. A mixed-methods, community-engaged study assessed the impact of WTD 2024 on participants. Data were gathered via pre- and post-event surveys, personal reflections, and social network analysis. Seventy-nine participants representing 27 countries of origin participated in the study. Key findings highlighted transformative learning, creation of a community with shared interests, enhanced advocacy, new collaborations, and leadership development. Participants reported greater empathy for people living with dementia and their care partners, deeper knowledge of dementia, and stronger personal commitment to inclusive practices. WTD 2024 cultivated cross-cultural collaboration and connection among diverse stakeholders. The initiative spurred innovative advocacy approaches, reinforced person-centered care principles, and provided a scalable model for participatory dementia programs. Walking the Talk for Dementia (WTD) 2024 combined multiple dimensions to transform perspectives on dementia. This research found high satisfaction, new collaborations, and individual impact. WTD integrated experiences of dementia in a journey of exploration and learning WTD enhanced empathy, personal purpose, and commitment to brain health advocacy. The WTD model has potential for global dissemination and influence on dementia policy.

In 2011, a workgroup of the Alzheimer's Association Research Roundtable introduced recommendations for detecting and monitoring amyloid-related imaging abnormalities (ARIA) in Alzheimer's disease (AD) clinical trials. Since then, anti-amyloid immunotherapies have received regulatory approval for AD treatment and are beginning to enter clinical practice, underscoring the importance of informing healthcare providers, researchers, and patients about ARIA's implications in real-world settings. In response, the Alzheimer's Association convened a new workgroup to review current knowledge of ARIA, including underlying mechanisms, clinical presentations, associated risk factors, mitigation strategies, radiologic detection methods, patients' perspectives in treatment decision-making, and outstanding challenges. Here, we outline key insights from this workgroup, highlighting that effective ARIA detection and monitoring in clinical practice requires adherence to robust protocols to mitigate risks and enhance patient safety. Limited availability of clinical and pathologic data on predictors of symptomatic and severe ARIA underscores the importance of continued real-world data collection.

The global rise in dementia prevalence, a major neurocognitive disorder, poses a significant challenge to aging populations. This study aimed to determine the prevalence of dementia and its associated risk factors among community-dwelling elderly in selected provinces of Iran. A cross-sectional study was conducted from October 2022 to March 2024, enrolling 58,228 individuals aged 60-75 years from two provinces (Qazvin and Yazd) selected via multi-stage, stratified random sampling. A multi-stage diagnostic protocol was employed, using validated Persian versions of the Geriatric Depression Scale (GDS), Abbreviated Mental Test Score (AMTS), Mini-Mental State Examination (MMSE), Functional Assessment Staging (FAST), and Montreal Cognitive Assessment (MoCA) with standardized cut-offs. Multivariable logistic regression was used to identify factors associated with dementia. After exclusions, the final analytical sample was 56,456 participants. The overall prevalence of dementia was 10.1%. Prevalence was significantly higher in women (13.2%) than in men (7.0%). In the adjusted model, female gender (aOR: 2.04, 95% CI: 1.92-2.15), older age (70-79&#xa0;years vs. 60-64&#xa0;years, aOR: 1.70, 95% CI: 1.59-1.82), widowhood (aOR: 1.50, 95% CI: 1.05-2.16), and lower educational attainment (illiterate vs. academic, aOR: 6.55, 95% CI: 5.43-7.91) were significantly associated with higher odds of dementia. This large-scale study reveals a substantial burden of dementia in the studied Iranian provinces. The identified risk factors, including female sex, advanced age, widowhood, and low education, highlight vulnerable subgroups and underscore the urgent need for targeted public health strategies focused on early detection, risk reduction, and support systems for the elderly in Iran.

To better characterize the genetic architecture underlying Alzheimer's disease (AD) and related dementia (ADRD), we performed a meta-analysis of European ancestry genome-wide association studies in 128,681 cases or proxy cases of ADRD and 849,833 (proxy) controls. We identified 91 genetic loci associated with ADRD risk, including 16 which are novel, and 56 which are specifically detected in clinically diagnosed AD cases. We also provide a list of 18 loci (15 novel) requiring further external validation. A polygenic score combining the effect of the ADRD loci except APOE was primarily associated with AD rather than non-AD pathology. Individuals in the 10th decile of the score had a 2-fold increased risk to present with Braak neurofibrillary tangles stage above 5 and moderate/severe neuritic amyloid plaque pathology at death compared to individuals in the median score group.

Lewy body dementia is a heterogeneous disease that is underdiagnosed and poorly understood. Pathologically, Lewy body dementia is characterised by the accumulation of intraneuronal aggregates of misfolded &#x3b1;-synuclein, known as Lewy bodies and Lewy neurites. The genetic architecture of Lewy body dementia is complex, involving both common genetic variants with small risk effects and rare genetic variants with large effects. Alzheimer's disease pathology frequently coexists with Lewy body pathology and influences the clinical presentation. A deeper understanding of the pathophysiological pathways, including mitochondrial dysfunction, lysosomal dysfunction, and neuroinflammation, can enhance disease modelling, and this knowledge will ultimately facilitate the development of therapeutic interventions. The biological relationships that Lewy body dementia shares with other neurodegenerative and psychiatric disorders might also be crucial for the development of therapeutic strategies.

The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized. Over 7500 total whole-genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool. Low PathSeq scores for human herpesvirus 6 (HHV-6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV-6 genome integration. This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV-6 may play a role in a subset of these patients. Over 7500 whole-genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV-6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.

Idiopathic achalasia (IA) is characterised by the degeneration of neurons in the myenteric plexus leading to an irreversible impaired oesophageal function. Although immune-mediated mechanisms have been proposed, the underlying aetiopathology of IA remains poorly understood. This study aimed to uncover the genetic risk architecture of IA. We carried out the first genome-wide association study (GWAS) on 4602 European patients with IA and 10&#x2009;766 ethnically-matched controls. A single nucleotide polymorphism (SNP) in HLA-DQB1 leading to an 8-amino acid insertion on the protein level conferred strongest IA risk (PQGPPPAG: p=3.27&#xd7;10-68, OR=2.45). Conditional analyses within the HLA locus revealed a complex genetic risk architecture. Three additional amino acid positions showed independent IA association (Omnibus p<5&#xd7;10-8). These refer to positions 41 and 130 in HLA-DQ&#x3b1;1, position 45 in HLA-DQ&#x3b2;1 and position 86 in HLA-DR&#x3b2;1. Together, these findings highlight the pivotal role of class II HLA genetic variation in IA pathogenesis. Outside HLA, three independent variants showed IA association (p<5&#xd7;10-8). One leads to an amino acid substitution with functional effect in PTPN22. Another risk variant leads to a downregulated expression of TNFSF8, TNFSF15 and TNC in immune cells. The third risk SNP is located near ZNF365, but the exact underlying cellular mechanism remains unknown. Beyond the single marker level, polygenic risk scores revealed that patients with IA can be stratified based on their genetic risk. In addition, IA shows a shared aetiopathology with Crohn's disease (rg=0.335). Integrating GWAS and single-cell RNA-sequencing data from the myenteric plexus showed that the memory T-cell type FOS+Tc4+CD8+ plays a central role in IA development (p=2.50&#xd7;10-19). This GWAS led to the identification of SNPs, cellular mechanisms and cell types that are involved in IA aetiopathology.

This study examined the association between the apolipoprotein E (APOE) &#x3b5;4 allele and cognitive performance, neuroimaging, and plasma biomarkers in Congolese older adults in the Democratic Republic of the Congo (DRC). Eighty-four participants (39 healthy controls [HCs], 45 with suspected dementia), aged 73.0 years on average, were assessed using the African Neuropsychology Battery, magnetic resonance imaging, and blood-based biomarkers. Regression models adjusted for age, sex, and education evaluated APOE's impact. APOE &#x3b5;4 was more prevalent in dementia cases than in HCs. Overall, APOE &#x3b5;4 status significantly affected naming and memory scores, mesial temporal and entorhinal cortex atrophy scores, and glial fibrillary acidic protein concentration levels. In HCs, it showed no significant impact on cognitive or neuroimaging tests, except for neurofilament light chain concentration levels. Among dementia participants, APOE &#x3b5;4 status influenced only naming and memory scores. APOE &#x3b5;4 carriers in this DRC cohort showed greater cognitive decline and neurodegeneration, highlighting its significant impact in African populations. Apolipoprotein E (APOE) &#x3b5;4 was more frequent in dementia cases than in healthy controls in a Democratic Republic of the Congo cohort. APOE &#x3b5;4 carriers showed greater cognitive decline, especially in memory and visuospatial skills. Neuroimaging findings revealed increased hippocampal atrophy and cortical thinning in carriers. Plasma biomarkers in dementia showed higher amyloid beta 40, phosphorylated tau181, neurofilament light chain, and tumor necrosis factor alpha levels. Findings underscore APOE &#x3b5;4's impact on neurodegeneration in African populations.

Caregiver support interventions can reduce depression symptoms for caregivers of persons living with cognitive impairment and dementia (PwCI). However, few studies have assessed the effect of caregiver counseling support on the health-care use of the PwCI. The objective of this study was to assess if caregiver participation in mental health counseling can slow health-care use in PwCI. The analysis included all PwCI with cognitive impairment identified through the electronic health records as seen in either the Wake Forest Memory Counseling Program (MCP), providing mental health counseling, and/or the Kulynych Geriatric Consult Clinic (KGCC), providing memory assessment and care, between August 1, 2016, and February 28, 2020. Health-care use (emergency department [ED] use and hospitalization) pre- and post-index date were compared between PwCI who received only medical care (MC) and those who received both medical and mental health care (MC+MHC) using a mixed effects logistic regression model adjusted for age, sex, race, ethnicity, KGCC visit type, and primary diagnosis. Hypothesis testing was accomplished with two-sided Wald tests, and odds ratios (ORs) were used to characterize effect sizes. Compared to the 1 year pre-index visit, PwCI who received medical care (MC) only experienced an increase in ED visits (OR 1.73, P < 0.0001) and hospitalizations (OR 1.42, P < 0.0001) in the 1 year post-index visit. In contrast, PwCI and caregivers who received medical + mental health care (MC+MHC)&#xa0;did not experience increases in ED visits (OR 1.13, P = 0.5104) or hospitalizations (OR 1.15, P = 0.4849). Compared to MC only, PwCI who received MC+MHC had significantly lower odds of post- versus pre-ED visits (OR 0.65, P = 0.0322) but not hospitalizations (OR 0.81, P = 0.3270). Providing mental health counseling to caregivers in addition to medical care for the PwCI may reduce ED visits among PwCI. This study tests whether caregiver participation in mental health counseling can slow health-care use in the person living with dementia (PLWD).PLWDs who received medical only visits experienced an increase in emergency department (ED) visits compared to those who received both medical and mental health care.Providing mental health counseling to caregivers in addition to medical care for the PLWD may reduce ED visits among PLWD.

Alzheimer's disease (AD) continues to pose a major public health challenge. Since its launch in 2004, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has played a pivotal role in advancing the field by providing a comprehensive, open-access, longitudinal dataset that integrates neuroimaging, biomarker, genetic, and clinical data related to AD. We used standard literature search methods to identify &#x223c;1830 publications from 2023 to mid-2025 that used ADNI data or samples. This review highlights key ADNI studies with direct clinical applications. We describe how these have impacted the development and validation of plasma biomarkers, improved clinical trials, assessed AD therapies, and developed methods for diagnosis and prediction using clinical, fluid, and imaging biomarkers. These contributions are underlain by an improved understanding of biological mechanisms of disease progression in AD and highlight ADNI's central role in advancing translational research and accelerating progress toward more effective, individualized care for patients with AD.