The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Stress internalization is a top risk for age-associated cognitive decline among older Chinese in the U.S.","authors":"Michelle H Chen, Yiming Ma, Charu Verma, Stephanie Bergren, William T Hu","doi":"10.1016/j.tjpad.2025.100270","DOIUrl":"10.1016/j.tjpad.2025.100270","url":null,"abstract":"<p><strong>Background: </strong>Behavioral and sociocultural factors are often examined in population-based studies as independent variables, yet latent factors often influence multiple behaviors all at once. This may be especially true in immigrant populations living in or near ethnic enclaves. Better characterization of internal or external factors underlying multiple behaviors is critical to modify the root causes of health-related behaviors.</p><p><strong>Objectives: </strong>To identify inter-relatedness of multiple internal (acculturation, behavior, well-being) and external (neighborhood & community) characteristics, as well as their influence on age-associated cognitive decline in a large group of non-demented older Chinese Americans living in the Chicago metropolitan area.</p><p><strong>Setting: </strong>Secondary data analysis of the Population Study of ChINese Elderly (PINE).</p><p><strong>Participants: </strong>1528 non-demented older Chinese Americans (aged 60+) who attended three waves of PINE.</p><p><strong>Design: </strong>Longitudinal cohort study.</p><p><strong>Intervention(s): </strong>Not applicable.</p><p><strong>Measurements: </strong>Three psychobehavioral and 3 sociocultural factors were included in factor analysis for independent variables; Chinese versions of the Mini-Mental State Examination, East Boston Memory Test, Digit Span Backward, and oral Symbol Digit Modalities Test were included in principal component analysis to derive dependent variables.</p><p><strong>Results: </strong>Factor analysis identified three main behavioral/sociocultural constructs: stress internalization, neighborhood/community cohesion, and external stress alleviation. Among these, only stress internalization - consisting of greater perceived stress, greater hopelessness, and lower conscientiousness - was associated with longitudinal decline in memory, while none with decline in executive functioning. Neither acculturation nor activity engagement was related to longitudinal decline in memory or executive functioning, even though participants with greater acculturation or activity engagement had better baseline cognitive performance.</p><p><strong>Conclusions: </strong>Only the factor underlying stress processing, hopelessness, and conscientiousness was associated with rates of longitudinal memory decline in this older non-demented Chinese American cohort. These maladaptive traits have been linked to the Asian model minority stereotype but all the same potentially modifiable. Limitations include potential selection bias, potential cultural inappropriateness of the measures, and limited cognitive test battery and clinical information.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100270"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene and genetic therapies in Alzheimer's disease and other dementias.","authors":"Robert C Alexander","doi":"10.1016/j.tjpad.2025.100313","DOIUrl":"10.1016/j.tjpad.2025.100313","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100313"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.","authors":"Dag Sehlin, Greta Hultqvist, Wojciech Michno, Ximena Aguilar, Amelia D Dahlén, Enrica Cerilli, Nadja M Bucher, Sara Lopes van den Broek, Stina Syvänen","doi":"10.1016/j.tjpad.2025.100214","DOIUrl":"10.1016/j.tjpad.2025.100214","url":null,"abstract":"<p><p>The emerging class of bispecific antibodies represents a significant advancement in Alzheimer's disease (AD) immunotherapy by addressing the limited brain concentrations achieved with conventional monoclonal antibodies. The majority of bispecific antibodies developed for AD treatment utilize transferrin receptor (TfR1)-mediated transcytosis to enhance blood-brain barrier (BBB) penetration, resulting in higher and more uniform brain concentrations compared to conventional antibodies. This improved delivery has demonstrated superior efficacy in reducing brain amyloid-beta (Aβ) burden. Additionally, TfR1-mediated delivery may help mitigate adverse effects such as amyloid-related imaging abnormalities (ARIA). This is likely achieved by a reduction in antibody accumulation at vascular Aβ deposits, resulting from the combined effects of lower dosing and a different brain entry route when using bispecific antibodies. Besides targeting Aβ, bispecific antibodies have been engineered to address other key pathological features of AD, including tau pathology and neuroinflammatory targets, which are critical drivers of disease progression. These antibodies also show promise in diagnostic applications, particularly as radioligands for antibody-based positron emission tomography (immunoPET), leveraging their rapid brain delivery and efficient and specific target engagement. Moreover, the principles of bispecific antibody technology have been adapted for use beyond immunotherapy. The incorporation of TfR1-binding domains into enzymes, antisense oligonucleotides, or viral vectors such as adeno-associated viruses broadens their therapeutic potential. These approaches may enable more efficient treatment strategies, not only for AD but also for other neurological disorders, by facilitating the delivery of diverse therapeutic agents across the BBB.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100214"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early detection of Alzheimer's disease using small RNAs. Results from the EPAD cohort.","authors":"Tobias Sikosek, Marco Heuvelman, Jagoda Mika, Mustafa Kahraman, Julia Jehn, Maurice Frank, Alberto Daniel-Moreno, Jessika Ceiler, Jasmin Skottke, Marta Sanchez-Delgado, Patrick Neubert, Christina Rudolf, Kaja Tikk, Rastislav Horos, Jeffrey L Cummings, Josie Butchart, Craig Ritchie, Jean Manson, Bruno R Steinkraus","doi":"10.1016/j.tjpad.2025.100257","DOIUrl":"10.1016/j.tjpad.2025.100257","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most common form of dementia, and early diagnosis is crucial to enable effective interventions. Currently, Alzheimer's disease is diagnosed through cognitive assessments, brain imaging and fluid biomarkers focused on determining amyloid (A) and, tau (T) protein levels as well as neurodegeneration (N) in the AT(N) framework. Prognostic biomarkers for predicting cognitive decline within the amyloid positive (Aβ+) individuals would further strengthen the framework.</p><p><strong>Objectives: </strong>This study evaluated small RNAs as novel auxiliary biomarkers, independent of the AT(N) framework, either alone or in combination with established protein markers, for detecting the earliest cognitive decline in AD.</p><p><strong>Design: </strong>The European Prevention of Alzheimer's Disease (EPAD) clinical trial platform is a prospective, multi-center study designed to investigate biomarkers for preclinical and prodromal AD.</p><p><strong>Setting: </strong>Peripheral whole blood RNA sequencing was performed on participants across Europe with no cognitive impairment or very mild cognitive impairment (MCI), stratified by cerebrospinal fluid amyloid levels.</p><p><strong>Participants: </strong>1,913 participants, 50 years or older and free of dementia diagnosis at enrollment, were analyzed.</p><p><strong>Intervention: </strong>(if any) Not applicable.</p><p><strong>Measurements: </strong>Ultra-deep small RNA sequencing was performed on whole blood samples using a refined blocking protocol to eliminate highly abundant erythroid small RNAs, and thereby to open sequencing bandwidth for the discovery of less abundant biomarker RNAs. Biomarker RNAs were deconvolved into plasma or blood cell origin and analyzed for functional relevance. We define high and low amyloid groups based on a cutoff on the p-tau₁₈₁/Aβ_1-42 ratio as determined from cerebrospinal fluid.</p><p><strong>Results: </strong>We identified a combination of small RNAs that predicted early cognitive decline (Clinical Dementia Rating of 0.5) with an area under the receiver-operator curve of ∼0.7. Notably, when focusing on individuals with cognitive decline and high amyloid burden (Aβ+), the predictive accuracy improved to an AUC of 0.77. This performance could be extended to the entire cohort when combining blood RNA and CSF amyloid markers (AUC 0.76). We conducted bioinformatic analyses to interrogate the likely functional relevance of these small RNAs, uncovering several links to dementia-relevant pathways, including neuronal, cardiovascular, and inflammatory activities. Our findings also suggest that small nucleolar RNAs warrant further investigation as potential disease-relevant markers, in addition to microRNAs.</p><p><strong>Conclusions: </strong>Integrating small RNA biomarkers with protein-based assays offers preliminary evidence for stratifying MCI, particularly within the amyloid positive continuum. Small","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100257"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of vitamin B₁₂ deficiency in a dementia cohort with hippocampal atrophy on MRI.","authors":"Asako Ueno, Tadanori Hamano, Miwako Nagata, Tomohisa Yamaguchi, Yoshinori Endo, Soichi Enomoto, Hirohiko Kimura, Masamichi Ikawa, Osamu Yamamura, Daiki Yamanaka, Yohei Kimura, Yasunari Nakamoto, Yasuhiro Nishiyama","doi":"10.1016/j.tjpad.2025.100265","DOIUrl":"10.1016/j.tjpad.2025.100265","url":null,"abstract":"<p><strong>Background: </strong>Vitamin deficiencies have been reported to cause brain atrophy. Hippocampal atrophy has been well reported in patients with dementia including Alzheimer's disease.</p><p><strong>Objectives: </strong>To investigate the association between hippocampal atrophy and vitamin deficiency DESIGN: Cross sectional study SETTING: Three sites in one country PARTICIPANTS: Overall, 567 patients who visited an outpatient dementia clinic and underwent MRI-VSRAD (Voxel-Based Specific RegionalAnalysis System for Alzheimer's Disease) were included in this study.</p><p><strong>Intervention: </strong>Patients with a hippocampal atrophy Z-score of < 2 were classified as normal (n = 323), and those with a Z-score of ≥ 2 were diagnosed with hippocampal atrophy (n = 244).</p><p><strong>Measurements: </strong>Vitamin B₁₂, folic acid, vitamin B₁, homocysteine, HbA1c, and creatinine levels were measured and their association with hippocampal atrophy was assessed. Age, MMSE (Mini Mental State Examination), and hippocampal atrophy were also evaluated.</p><p><strong>Results: </strong>In the hippocampal atrophy group, the frequency of vitamin B₁₂ deficiency was higher (p < 0.022), MMSE score was lower (p < 0.0001), and age was higher (p < 0.0001) than that in the normal group (Mann-Whitney U test). Patients with vitamin B₁₂ deficiency (odds ratio, 3.46) and low MMSE score (odds ratio, 2.24) had an increased risk of hippocampal atrophy.</p><p><strong>Conclusion: </strong>Vitamin B₁₂ deficiency was associated with hippocampal atrophy detected by VSRAD analysis. Therefore, early vitamin B₁₂ supplementation should be considered in patients with deficiencies to reduce dementia risk.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100265"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The singapore dementia prevention programme: Ten years on and looking ahead.","authors":"Lei Feng, Kaisy Xinhong Ye, Lee Gan Goh, Ee-Heok Kua","doi":"10.1016/j.tjpad.2025.100272","DOIUrl":"10.1016/j.tjpad.2025.100272","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100272"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multimodal lifestyle intervention complemented with epigallocatechin gallate to prevent cognitive decline in APOE- ɛ4 carriers with Subjective Cognitive Decline: a randomized, double-blinded clinical trial (PENSA study).","authors":"Laura Forcano, Natalia Soldevila-Domenech, Anna Boronat, Gonzalo Sánchez-Benavides, Albert Puig-Pijoan, Thais Lorenzo, Ana Aldea-Perona, Marc Suárez-Calvet, Aida Cuenca-Royo, Juan Domingo Gispert, Maria Gomis-Gonzalez, Carolina Minguillón, Patrícia Diaz-Pellicer, Karine Fauria, Iris Piera, Klaus Langohr, Mara Dierssen, Nieves Pizarro, Esther Mur-Gimeno, Oriol Grau-Rivera, José Luis Molinuevo, Rafael de la Torre","doi":"10.1016/j.tjpad.2025.100271","DOIUrl":"10.1016/j.tjpad.2025.100271","url":null,"abstract":"<p><strong>Background: </strong>The potential of dietary compounds to enhance the effects of multimodal lifestyle interventions (MLIs) on cognition in individuals at high risk of cognitive impairment remains unclear.</p><p><strong>Objectives: </strong>To assess whether the addition of a green tea extract enriched with epigallocatechin-3-gallate (EGCG) enhances the effects of an MLI.</p><p><strong>Design: </strong>Double-blind, randomized, two-arm, and placebo-controlled trial. Exploratory comparisons were made with a non-randomized group (NRG) receiving healthy lifestyle recommendations.</p><p><strong>Setting: </strong>Population-based study conducted in Barcelona, Spain PARTICIPANTS: APOE-ɛ4 carriers aged 60-80 with subjective cognitive decline INTERVENTION: A 12-month intensive MLI including dietary counseling, guided physical activity, and cognitive stimulation, combined with EGCG (5-6 mg/kg) or placebo, followed by a 3-month washout.</p><p><strong>Measurements: </strong>Primary endpoint was change in the modified Preclinical Alzheimer Cognitive Composite (PACC-exe) score.</p><p><strong>Results: </strong>129 participants (65.1% 84 women, aged 66.7±5.5 years) were enrolled (52 MLI+EGCG, 52 MLI+placebo and 25 NRG), with126 (97.7%) included in the modified intention-to-treat analysis. After 12 months, no statistically significant difference was observed between MLI+EGCG and MLI+placebo in the PACC-exe (adjusted mean difference [AMD]: 0.12; 95%CI: -0.01, 0.24; p=0.061). However, participants in the MLI+EGCG group were 2.6 times more likely to show a reliable cognitive improvement. In exploratory analyses following a 3-month washout, the MLI+EGCG group showed significant cognitive benefits compared to the MLI+placebo (AMD: 0.19; 95%CI: 0.06, 0.32; p=0.005). Exploratory comparisons with the NRG also suggested greater gains in cognition and dementia risk reduction in both MLI groups, particularly with EGCG.</p><p><strong>Conclusions: </strong>While the primary outcome was not met, this proof-of-concept trial suggests that combining MLIs with EGCG warrants further investigation in larger, confirmatory studies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100271"},"PeriodicalIF":7.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between traumatic brain injury and the prevalence of Alzheimer's disease dementia and behavioral and psychological symptoms of dementia: A retrospective cohort study.","authors":"Han-Kyeol Kim, Sojeong Park, Sung-Woo Kim, Yeonju Jin, Hokyung Lee, Jin Yong Hong, Ickpyo Hong, Min Seok Baek","doi":"10.1016/j.tjpad.2025.100360","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100360","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury is an environmental risk factor that may accelerate the progression of Alzheimer's disease and behavioral and psychological symptoms of dementia in patients with mild cognitive impairment.</p><p><strong>Objectives: </strong>To investigate whether traumatic brain injury in patients with mild cognitive impairment is associated with an increased risk of progression to Alzheimer's disease dementia and behavioral and psychological symptoms of dementia.</p><p><strong>Design: </strong>A retrospective cohort study using the Korean National Health Insurance Service database.</p><p><strong>Setting: </strong>National-level health data covering healthcare utilization, diagnoses, prescriptions, and procedures in South Korea from January 2012 to December 2021.</p><p><strong>Participants: </strong>Patients diagnosed with mild cognitive impairment between January 1, 2013, and December 31, 2016, were followed until Alzheimer's disease dementia diagnosis, behavioral and psychological symptoms of dementia occurrence, death, or December 31, 2021. These patients were classified into two groups according to the presence of traumatic brain injury during the follow-up period.</p><p><strong>Measurements: </strong>Age at the time of mild cognitive impairment diagnosis, sex, income level, the presence of several chronic conditions, presence of traumatic brain injury, progression of Alzheimer's disease dementia, and behavioral and psychological symptoms of dementia RESULTS: We assessed 452,718 patients (mean age: 67.16 years). Traumatic brain injury was significantly associated with an increased risk of Alzheimer's disease dementia progression (hazard ratio = 1.252, 95 % confidence interval: 1.206-1.301), particularly among patients aged <65 years (hazard ratio = 1.560, 95 % confidence interval: 1.391-1.749), and was linked to a higher risk of behavioral and psychological symptoms of dementia following Alzheimer's disease dementia diagnosis (hazard ratio = 1.300, 95 % confidence interval: 1.181-1.431).</p><p><strong>Conclusions: </strong>Our results underscore the importance of traumatic brain injury prevention in patients with mild cognitive impairment for mitigating the progression and neuropsychiatric complications of Alzheimer's disease.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100360"},"PeriodicalIF":7.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain lymphatic drainage pathways, deep cervical lymphatic surgery, and current insights: A systematic review.","authors":"Theodore Lahmar, Francois Thuau, Gaelle Pinard, Claire Boutoleau-Bretonniere, Pierre Perrot, Ugo Lancien","doi":"10.1016/j.tjpad.2025.100335","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100335","url":null,"abstract":"<p><p>The discovery of the glymphatic system and the later rediscovery of the meningeal lymphatic network have significantly changed our understanding of central nervous system (CNS) waste clearance. Aging is linked to a gradual decline in these clearance pathways, resulting in waste buildup. As a result, therapeutic strategies targeting cerebral lymphatic function have garnered growing interest, with lymphatic surgery emerging as a promising option. We conducted a review until July 2025, providing an overview of the potential of lymphatic surgical techniques to enhance CNS metabolic waste clearance pathways as a therapeutic approach for brain lymphatic system disorders. Currently available data are limited, nine publications addressing this approach. These studies explore an innovative technique involving lymphatico-venous anastomoses (LVA) targeting deep cervical lymphatic vessels to promote clearance for the treatment of Alzheimer's or Parkinson's diseases. Cerebral lymphatic drainage is critical for effective brain waste elimination such as amyloid-β, phosphorylated tau, and α-synuclein, which are linked to neurodegenerative diseases. Viewing these lymphatic dysfunctions as a form of \"cerebral lymphedema,\" LVA, already used in treating peripheral lymphedema, shows potential as a therapeutic approach. Although clinical evidence is still limited, lymphatic supermicrosurgery presents promising therapeutic possibilities for neurodegenerative diseases and other conditions related to impaired CNS lymphatic outflow.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100335"},"PeriodicalIF":7.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma and neurostructural biomarkers in the clinical-biological characterization of early stages of the Alzheimer's disease continuum: findings from the Compostela Aging Study.","authors":"Montserrat Zurrón, Arturo Xosé Pereiro, Ana Isabel Rodriguez-Perez, Santiago Galdo-Álvarez, Juan José Ansede, Cristina Lojo-Seoane, Mónica Lindín, David Facal, Miguel Ángel Rivas-Fernández, María Campos-Magdaleno, Ángel Carracedo, José Luis Labandeira-Garcia, Fernando Díaz","doi":"10.1016/j.tjpad.2025.100331","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100331","url":null,"abstract":"<p><p>Recent technical advances in peripheral blood analysis have enabled precise quantification of Alzheimer´s Disease (AD) biomarkers in the early stages of the AD continuum, in an economical, non-invasive and safe manner. The main objective of this study was to contribute to the clinical-biological characterization of the initial stages of cognitive impairment by measurement of blood and neurostructural AD biomarkers in groups of participants classified according to their cognitive clinical phenotype. Plasma concentrations of p-tau217, p-tau181, total tau, neurofilament light chain and amyloid-β 42/40 ratio biomarkers were measured along with APOE gene variants, hippocampal volume and cortical thickness of the AD signature regions. The cohort of 329 participants included Cognitively Unimpaired (CU), Subjective Cognitive Decline (SCD), single-domain amnestic Mild Cognitive Impairment (sd-aMCI), multidomain aMCI (md-aMCI), and single-domain non-amnestic MCI (sd-naMCI) groups. P-tau217 concentrations were significantly higher in the md-aMCI and sd-aMCI groups than in the CU, SCD and sd-naMCI groups. P-tau181 concentrations were significantly higher in md-aMCI group than in CU, SCD and sd-naMCI groups. Hippocampal volume and AD signature cortical thickness were significantly lower in the md-aMCI group than in the CU, SCD and sd-naMCI groups. No across group differences were found in the distribution of carriers/non-carriers of APOE-ε4. Mediation analysis revealed that hippocampal volume and AD signature cortical thickness mediated the relationship between p-tau217 and p-tau181 levels and cognitive performance. Sd-aMCI and md-aMCI represent two distinct and sequential clinical-biological stages of the AD continuum. Conversely, sd-naMCI does not appear to be associated with AD pathology. Finally, the SCD group does not seem to display a higher risk of progression along the AD continuum than the CU group.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100331"},"PeriodicalIF":7.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}