Alzheimer's Research & Therapy最新文献

{"title":"Correction: Investigating the Aβ and tau pathology in autosomal dominant Alzheimer's disease: insights from hybrid PET/MRI and network mapping.","authors":"Zhi Zhou, Qigeng Wang, Linwen Liu, Qi Wang, Xiaojun Zhang, Can Li, Jiajin Liu, Yidan Wei, Jin Gao, Liping Fu, Ruimin Wang","doi":"10.1186/s13195-025-01730-w","DOIUrl":"https://doi.org/10.1186/s13195-025-01730-w","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"87"},"PeriodicalIF":7.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships between blood pressure indicators and fluid biomarkers of brain aging in functionally intact older adults.","authors":"Anna M VandeBunte, Bailey L Ortiz, Emily W Paolillo, Rowan Saloner, Valentina Diaz, Shubir Dutt, Claire J Cadwallader, Coty Chen, Argentina Lario Lago, Julio C Rojas, Brandon Chan, Isabel Sible, Joel H Kramer, Kaitlin B Casaletto","doi":"10.1186/s13195-025-01731-9","DOIUrl":"https://doi.org/10.1186/s13195-025-01731-9","url":null,"abstract":"<p><strong>Background: </strong>Dementia risk is significantly shaped by cardiovascular health, with elevated blood pressure emerging as a key risk factor for adverse brain aging. Blood biomarkers such as pTau181, Aβ42/40, NfL, and GFAP have improved our understanding of dementia pathophysiology, however, few studies have explored how specific blood pressure metrics relate to biomarker levels, which could inform personalized dementia prevention strategies as these biomarkers move into clinic. We examined how different blood pressure metrics associated with molecular markers of astrocytic activation (GFAP), neuronal axon breakdown (NfL), and Alzheimer's disease pathobiology (pTau181, Aβ42/40) in plasma.</p><p><strong>Methods: </strong>109 functionally intact (Clinical Dementia Rating Scale = 0) older adults completed blood draws with plasma assayed for Aβ42/40, GFAP, NfL, and pTau181 (Quanterix Simoa) and in-lab blood pressure quantification. Blood pressure metrics included diastolic blood pressure, systolic blood pressure, and pulse pressure (systolic minus diastolic). Separate regression models evaluated plasma biomarkers as a function of each blood pressure metric, adjusting for age and biological sex. Interaction models tested whether relationships between blood pressure metrics and plasma biomarkers differed by sex, age, or APOE-ε4 status.</p><p><strong>Results: </strong>With the exception of Aβ42/40, higher pulse pressure related to higher levels of all plasma biomarkers examined (pTau181, NfL, GFAP). Additionally, higher systolic blood pressure related to higher pTau181, while diastolic blood pressure did not meaningfully associate with any biomarker. Interaction models revealed a significantly stronger relationship between elevated pulse pressure and higher GFAP concentrations in females compared to males, as well as a significantly stronger association between elevated pulse pressure and lower Aβ42/40 plasma concentrations in APOE-ε4 carriers compared to non-carriers.</p><p><strong>Conclusions: </strong>Our findings suggest that elevated pulse pressure, and to a lesser extent systolic blood pressure, are associated with increased Alzheimer's disease and neurodegenerative (axonal and astrocytic health) biology among typically aging adults. These associations underscore the importance of blood pressure management, particularly pulse pressure, for reducing dementia risk. Cardiovascular health may be incorporated with biomarkers to further personalize dementia prevention and management strategies.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"85"},"PeriodicalIF":7.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abdominal obesity and the risk of young-onset dementia in women: a nationwide cohort study.","authors":"Ye Seul Yang, Kyungdo Han, Dae Young Cheon, Minwoo Lee","doi":"10.1186/s13195-025-01738-2","DOIUrl":"https://doi.org/10.1186/s13195-025-01738-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>The association between obesity and young-onset dementia (YOD, defined as dementia diagnosed before age 65) is established, but the specific impact of abdominal obesity in women remains unclear. Abdominal obesity, driven by excess visceral fat, may increase dementia risk through metabolic and vascular pathways. We investigated the association between abdominal obesity and YOD risk in women using a large nationwide cohort.</p><p><strong>Methods: </strong>We analyzed 964,536 Korean women aged 40-60 years who underwent national health checkups in 2009. General obesity was defined by body mass index (BMI), and abdominal obesity was categorized by waist circumference (WC) into < 75 cm, 76-84 cm, 85-94 cm, and ≥ 95 cm. YOD was identified using ICD-10 codes and dementia medication prescriptions. Hazard ratios (HRs) for YOD were estimated using multivariable Cox proportional hazard models adjusted for lifestyle and clinical factors.</p><p><strong>Results: </strong>Over a median follow-up of 8.2 years, YOD incidence increased progressively with higher WC. Women with WC ≥ 95 cm had a 55% increased risk of YOD (HR 1.55; 95% CI 1.34-1.79) compared to those with WC < 75 cm. The association was particularly strong for vascular dementia (VD), with HR 1.83 (95% CI 1.30-2.57). By contrast, BMI showed a U-shaped relationship, with the lowest YOD risk observed in women with normal BMI (18.5-22.9 kg/m²), and significantly elevated risks in both underweight (BMI < 18.5 kg/m²; HR 1.39, 95% CI 1.13-1.71) and morbidly obese women (BMI ≥ 30 kg/m²; HR 1.26, 95% CI 1.10-1.45).</p><p><strong>Discussion: </strong>Abdominal obesity is a significant, independent risk factor for YOD in women, particularly for VD. These findings underscore the importance of addressing abdominal obesity in middle-aged women to reduce dementia risk.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"86"},"PeriodicalIF":7.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of nucleos(t)ide analogue therapy on the incidence of Alzheimer's disease in patients with chronic hepatitis B virus infection.","authors":"Jihye Lim, Hyundam Gu, Hyunji Sang, Su Jin Jeong, Ha Il Kim","doi":"10.1186/s13195-025-01729-3","DOIUrl":"https://doi.org/10.1186/s13195-025-01729-3","url":null,"abstract":"<p><strong>Background: </strong>Long-term therapy with nucleos(t)ide analogs (NUCs) is inevitable for chronic hepatitis B (CHB) patients. However, how NUC therapy on the developing Alzheimer's disease (AD) in these patients remains controversial.</p><p><strong>Methods: </strong>This retrospective cohort study used the Korean National Health Insurance Service claims database from January 1, 2013, to December 31, 2013, treatment naïve CHB patients and those without previously diagnosed with AD. Participants were followed from the index date until either the diagnosis of AD or the study's conclusion on December 31, 2021. The primary outcome was the incidence of AD, compared between the group with initiated NUC therapy (n = 18,365) at cohort entry and the group without NUC therapy (n = 212,820).</p><p><strong>Results: </strong>During the study, 416 patients were diagnosed with AD. After propensity-score matching (18,365 pairs), the 5- to 7-year follow-up showed a significantly lower hazard ratio (HR) in the NUC-treated group compared to the untreated group (HR 0.31-0.40), with HRs remaining constant over time. Subgroup analysis showed more pronounced benefits of NUC therapy in patients under 65 years (HRs: 0.22 vs. 1.23; P < 0.05) and those without dyslipidemia (HRs: 0.14 vs. 1.09; P < 0.05). Protective effects were also observed across subgroups with hypertension, chronic kidney disease, heart disease, and a history of brain trauma, consistent with AD risk factor trends.</p><p><strong>Conclusions: </strong>Our study analyses suggest that NUC therapy appears to have a protective effect against the development of AD in patients with CHB.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"84"},"PeriodicalIF":7.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: γ‑Secretase modulator resistance of an aggressive Alzheimer‑causing presenilin mutant can be overcome in the heterozygous patient state by a set of advanced compounds.","authors":"Johannes Trambauer, Rosa Maria Rodriguez Sarmiento, Holly J Garringer, Katja Salbaum, Liliana D Pedro, Dennis Crusius, Ruben Vidal, Bernardino Ghetti, Dominik Paquet, Karlheinz Baumann, Lothar Lindemann, Harald Steiner","doi":"10.1186/s13195-025-01723-9","DOIUrl":"https://doi.org/10.1186/s13195-025-01723-9","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"83"},"PeriodicalIF":7.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced associations between subjective cognitive concerns and blood-based AD biomarkers using a novel EMA approach.","authors":"Ángel García de la Garza, Caroline Nester, Cuiling Wang, Jacqueline Mogle, Nelson Roque, Mindy Katz, Carol A Derby, Richard B Lipton, Laura Rabin","doi":"10.1186/s13195-025-01720-y","DOIUrl":"https://doi.org/10.1186/s13195-025-01720-y","url":null,"abstract":"<p><strong>Background: </strong>Subjective cognitive concerns (SCC) have emerged as important early indicators of Alzheimer's disease (AD) risk. Traditional measures of SCC rely on recall-based assessments, which may be limited in capturing real-time fluctuations in cognitive concerns. Ecological Momentary Assessment (EMA) offers a promising alternative by providing real-time data. This study aimed to link SCC assessed via EMA and traditional measures with blood-based AD biomarkers in a diverse, dementia-free, community-based sample based in the Bronx, NY.</p><p><strong>Methods: </strong>Einstein Aging Study (EAS) participants underwent in-person, recall-based assessments of SCC during an in-clinic visit. Additionally, EMA SCC assessments were collected once per day over two weeks. Linear regressions were conducted to examine the relationships between SCC variables and plasma biomarkers adjusted for demographics and mild cognitive impairment (MCI) status.</p><p><strong>Results: </strong>In N = 254 participants, EMA-reported SCCs demonstrated significant associations with AD biomarkers, particularly p-tau181 (β = 0.21, p = 0.001). Further, significant associations remain across both cognitive (cognitively unimpaired vs. MCI) and racial groups. In contrast, traditional SCC measures exhibited limited associations with these biomarkers. The findings highlight the added value of EMA in capturing SCCs that could indicate early ADRD risk.</p><p><strong>Conclusions: </strong>EMA provides a more dynamic and potentially sensitive method for detecting early AD risk compared to traditional SCC assessments. These real-time measures could enhance early detection and clinical intervention, particularly in diverse and under-resourced populations. This study underscores the potential of EMA for broad applicability and inclusivity in monitoring AD progression and facilitating early therapeutic interventions.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"82"},"PeriodicalIF":7.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel CSF β-synuclein-specific assays signal early synaptic degeneration in Alzheimer's disease.","authors":"Sherif Bayoumy, Julie Goossens, Charlotte De Rocker, Senna Y Sie, Nolan J Barrett, Wiesje M van der Flier, Charlotte E Teunissen, Eugeen Vanmechelen, Inge M W Verberk","doi":"10.1186/s13195-025-01716-8","DOIUrl":"https://doi.org/10.1186/s13195-025-01716-8","url":null,"abstract":"<p><strong>Background: </strong>Beta-synuclein (β-syn), measured at N-terminal epitopes, is an emerging cerebrospinal fluid (CSF) biomarker for synaptic degeneration in Alzheimer's disease (AD). Targeting the mid-region or C-terminus of β-syn may enhance analytical specificity due to the distinct structures of these regions across the synuclein protein family, unlike targeting the N-terminus, which is conserved across the family. This study aimed to confirm that β-syn is a promising CSF biomarker in AD, using novel assays designed to target different regions of β-syn, to investigate whether these regions are differentially affected in AD.</p><p><strong>Methods: </strong>We developed two novel CSF β-syn-specific ELISAs targeting mid-region and C-terminus epitopes and assessed their analytical performance. Using these novel assays in combination with the established N-terminus ELISA, we analyzed a proof-of-concept cohort comprising biomarker-confirmed AD (n = 25) and non-AD subjects (n = 25) and a larger clinical cohort (n = 160) from the Amsterdam Dementia Cohort, wich included 41 individuals with subjective cognitive decline (SCD, controls; AD biomarker negative; 64.3 ± 3.3 years, 23 females), 39 with SCD (AD biomarker positive; 65.7 ± 3.1 years, 17 females), 40 with mild cognitive impairment due to AD (MCI-AD; 66.2 ± 2.9 years, 20 females), and 40 with AD dementia (AD-dem; 65.3 ± 3.4 years, 20 females).</p><p><strong>Results: </strong>Both the mid-region and C-terminus assays demonstrated reliable analytical performance. All assays consistently detected β-syn in all clinical samples above their limits of detection, with a good average intra-assay coefficient of variation (range of the three assays: 2.7-6.5%CV) in the proof-of-concept cohort and clinical cohort (range of the three assays: 3.9-7.5%CV). CSF β-syn levels, with all the assays, were significantly elevated in all the AD groups compared with the controls in both cohorts. The diagnostic performance of the assays for distinguishing AD patients from controls was comparable (Delong's p > 0.05, AUC 0.71-0.80). Notably, mid-region β-syn significantly differentiated SCD-AD patients from AD-dem patients (p = 0.035) and MCI-AD patients at a trend level. Only mid-region and C-terminal levels correlated with MMSE scores (mid-region rho = -0.22, p = 0.006; C-terminal rho = -0.19, p = 0.016; N-terminus rho = -0.14, p = 0.069).</p><p><strong>Conclusion: </strong>Our novel assays demonstrated good analytical and clinical performance. CSF β-syn reliably indicates early synaptic degeneration in AD. The mid-region assay uniquely differentiated SCD-AD from AD-dem, showing promise for early disease detection.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"81"},"PeriodicalIF":7.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term surveillance of the anti-amyloid monoclonal antibody lecanemab: rights and duties of pharmacovigilance.","authors":"Monia Donati, Angela Boccia, Fabrizio De Ponti, Elisabetta Poluzzi, Emanuel Raschi","doi":"10.1186/s13195-025-01699-6","DOIUrl":"https://doi.org/10.1186/s13195-025-01699-6","url":null,"abstract":"<p><p>The anti-amyloid monoclonal antibody lecanemab received the US accelerated approval for mild cognitive impairment or mild dementia stage of Alzheimer disease in January 2023, which was converted into traditional approval in June 2023. However, its regulatory assessment in Europe is still ongoing, and the European Commission has asked the Committee for Medicinal Products for Human Use of the European Medicines Agency to consider an update on the safety of lecanemab. Thus, timely post-marketing real-life studies are essential to clarify its long-term safety profile and to establish relevant place in therapy. In this regard, a recent study by Xing et al., analyzed individual case safety reports (ICSRs) collected in the Food and Drug Administration Adverse Event Reporting System (FAERS), a consolidated pharmacovigilance archive. In this Matters Arising article, we highlighted important methodological aspects that should not be overlooked by clinicians who are not fully familiar with this kind of study (the so-called disproportionality analysis through the case/non-case design), thus supporting enhanced awareness of stakeholders on interpretation, limitations and opportunities of FAERS data. To this end, we focused on the unexpected signal of pancreatic carcinoma raised by Xing et al., attempted to replicate the statistical findings and also provided a descriptive inspection of ICSRs: these are current rights and duties of modern pharmacovigilance to ensure evidence-based decision making.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"80"},"PeriodicalIF":7.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atrophy trajectories in Alzheimer's disease: how sex matters.","authors":"Anna Inguanzo, Konstantinos Poulakis, Javier Oltra, Silvia Maioli, Anna Marseglia, Daniel Ferreira, Rosaleena Mohanty, Eric Westman","doi":"10.1186/s13195-025-01713-x","DOIUrl":"https://doi.org/10.1186/s13195-025-01713-x","url":null,"abstract":"<p><strong>Introduction: </strong>Longitudinal subtypes in Alzheimer's disease (AD) have been identified based on their distinct brain atrophy trajectories, encompassing mediotemporal and cortical pathways. These subtypes include minimal atrophy, limbic predominant, limbic predominant plus, diffuse atrophy and hippocampal sparing. The impact of sex on the progression of these subtypes remains a crucial area of investigation.</p><p><strong>Methods: </strong>We analysed MRI data from 320 amyloid-β positive individuals with AD from three international cohorts (ADNI, J-ADNI and AIBL). Longitudinal clustering was conducted to identify atrophy trajectories over eight years from the clinical disease onset, with separate trajectories delineated for women and men.</p><p><strong>Results: </strong>Women consistently exhibited earlier hippocampal atrophy and a higher burden of white matter abnormalities compared to men, yet women displayed less cognitive decline over time. Additionally, specific risk factors and distinct neuropsychiatric symptoms were associated with sex within specific trajectories.</p><p><strong>Conclusions: </strong>AD subtypes show sex-specific differences in disease progression, highlighting the need to account for these differences from the early disease stages. Integrating imaging biomarkers with sex differences can enable the identification of more precise treatments for each patient, ensuring that both women and men have equal access to tailored care.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"79"},"PeriodicalIF":7.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticipatory reaching motor behavior characterizes patients within the Alzheimer's disease continuum in a virtual reality environment.","authors":"Alessia de Nobile, Ilaria Borghi, Paolo De Pasquale, Denise Jennifer Berger, Antonella Maselli, Francesco Di Lorenzo, Elena Savastano, Martina Assogna, Andrea Casarotto, Daniele Bibbo, Silvia Conforto, Francesco Lacquaniti, Giacomo Koch, Andrea d'Avella, Marta Russo","doi":"10.1186/s13195-025-01726-6","DOIUrl":"10.1186/s13195-025-01726-6","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is characterized by progressive declines in cognitive and motor functions, impairing daily activities. Traditionally, AD diagnosis relies on cognitive assessments, but emerging evidence highlights motor function deficits as early indicators of AD and Mild Cognitive Impairment (MCI). These motor declines, which often precede cognitive symptoms, include slower and less accurate reaching movements. This study explored reaching actions in a Virtual Reality (VR) environment in AD and MCI patients to identify motor deficits and their link to cognitive decline.</p><p><strong>Methods: </strong>The study involved 61 right-handed participants (19 AD, 21 MCI, and 21 healthy age-matched controls), screened for cognitive health using a Mini-Mental State Examination (MMSE). Participants performed upper-limb motor tasks (sequentially reaching targets) in a Virtual Reality (VR). Kinematic data was recorded and analyzed focusing on task success rate, frequency of anticipatory responses, and direction of anticipatory responses. Statistical analysis was performed using Generalized Linear Mixed Models to differentiate the three groups of participants based on performance metrics, anticipation behavior, and the correlation between anticipation rate and MMSE score.</p><p><strong>Results: </strong>Both AD and MCI patients showed more anticipatory responses than healthy controls (HC), inversely related to success rates and cognitive function. AD patients exhibited lower success rates and a higher frequency of anticipatory responses, often biased toward previous trial targets, suggesting impaired motor planning or difficulty adapting to new cues. MCI patients showed an intermediate pattern, with more anticipatory responses than HC but comparable success rates. These results highlight the crucial role of anticipatory behavior in motor task performance, with AD patients displaying the most pronounced deficits.</p><p><strong>Conclusions: </strong>This study highlights significant impairments of reaching movements in AD patients, particularly in terms of anticipatory behavior and success rates. The observed deficits suggest that kinematic metrics could serve as early biomarkers for diagnosis and intervention. These findings emphasize the importance of combining cognitive and sensorimotor assessments for the early detection of AD-related motor dysfunctions. Additionally, they highlight the potential of VR-based motor rehabilitation as a promising approach to address sensorimotor deficits in the AD continuum, improving both motor and cognitive outcomes.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"78"},"PeriodicalIF":7.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}