Alzheimer's & Dementia最新文献

{"title":"Novel blood-based proteomic signatures across multiple neurodegenerative diseases","authors":"Robert Durcan, Amanda Heslegrave, Peter Swann, Julia Goddard, Leonidas Chouliaras, Alexander G. Murley, George Savulich, W. Richard Bevan-Jones, Owen Swann, Nicholas J. Ashton, Kaj Blennow, William McEwan, Henrik Zetterberg, James B. Rowe, John T. O'Brien, Maura Malpetti","doi":"10.1002/alz.70116","DOIUrl":"https://doi.org/10.1002/alz.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Blood-based biomarkers have the potential to support early and accurate diagnoses of neurodegenerative diseases, which are sensitive to molecular pathology and are predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Serum from people with Alzheimer's disease (<i>N</i> = 36), Lewy body dementia (<i>N</i> = 34), frontotemporal dementia (<i>N</i> = 36), and progressive supranuclear palsy (<i>N</i> = 36) and age-matched controls (<i>N</i> = 30) was analyzed with the nucleic acid linked immuno-sandwich assay (NULISA) central nervous system panel (≈ 120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition-specific proteomic biomarkers, while neurofilament light chain, corticotropin-releasing hormone, CD276, and a data-driven inflammation pattern were significant transdiagnostic outcome predictors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We tested the novel technology nucleic acid linked immuno-sandwich assay (NULISA) in people with diverse neurodegenerative diseases, which demonstrated high sensitivity and reliability for detecting multiple biomarkers in serum samples.</li>\u0000 \u0000 <li>We compared the NULISA central nervous system serum results to single molecule array (Simoa) plasma assays for phosphorylated tau (p-tau)217, p-tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein, finding strong correlations.</li>\u0000 \u0000 <li>Increased levels of serum NfL were identified across all patient groups and most elevated in the frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) cohorts, while p-tau epitopes were the most significant markers in patients with Alzheimer's disease (AD) and Lewy body dementia.</li>\u0000 \u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707448","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":"Associations among sleep quality, sleep duration, and Alzheimer's disease biomarkers: A systematic review and meta-analysis","authors":"Chun-Lin Chen,&nbsp;Miao-Yu Zhang,&nbsp;Zhi-Lin Wang,&nbsp;Jia-Hui Deng,&nbsp;Yan-Ping Bao,&nbsp;Jie Shi,&nbsp;Lin Lu,&nbsp;Le Shi","doi":"10.1002/alz.70096","DOIUrl":"https://doi.org/10.1002/alz.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Although sleep disturbances are widely recognized as risk factors for cognitive decline and Alzheimer's disease (AD), their influence on AD biomarkers remains unclear. This study aimed to clarify whether sleep quality or sleep duration affect amyloid beta (Aβ) and tau levels in plasma, cerebrospinal fluid (CSF), and positron emission tomography (PET) in non-demented populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>PubMed, Web of Science, and Embase were systematically searched up to February 2025.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In total, 30 studies were included comprising 14,997 subjects. Individuals with poor sleep quality exhibited greater PET Aβ burden and higher Aβ42 levels in plasma than those with good sleep quality. Shorter sleep duration was associated with higher Aβ burden on PET. However, no association between either sleep quality or sleep duration and tau levels was found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Sleep may be a modifiable marker of early AD management by modulating Aβ levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>lPoor sleep quality and shorter sleep duration were significantly associated with higher amyloid beta (Aβ) burden detected by positron emission tomography (PET) in non-demented populations. Poor sleep quality was also associated with elevated Aβ42 levels in plasma.</li>\u0000 \u0000 <li>lNo significant associations were found between sleep quality or sleep duration and tau levels in plasma, cerebrospinal fluid, or PET.</li>\u0000 \u0000 <li>lInterventions targeting sleep could serve as a viable and low-cost prevention strategy for early management of Alzheimer's disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707444","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":"Efficacy of Communication Bridge-2 for primary progressive aphasia: A randomized controlled trial of communication intervention","authors":"Emily Rogalski,&nbsp;Matthew Bona,&nbsp;Marissa Esparza,&nbsp;Ollie Fegter,&nbsp;Rhiana Schafer,&nbsp;Aimee Mooney,&nbsp;Melanie Fried-Oken,&nbsp;Alfred Rademaker,&nbsp;Angela Roberts","doi":"10.1002/alz.70088","DOIUrl":"https://doi.org/10.1002/alz.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Primary progressive aphasia (PPA), a language-based neurodegenerative dementia, negatively impacts communication and quality of life. Previous non-pharmacologic interventions show promise but lack efficacy trials. Here, outcomes are provided from Communication Bridge-2 (CB2), a speech-language randomized controlled trial (RCT) for PPA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>CB2 is the first Phase 2, Stage II, parallel-group RCT delivered via video chat with global enrollment. Ninety-five dyads were randomized into one of two speech-language intervention arms. Primary outcomes included communication confidence and participation measures. Marginal linear models assessed efficacy across ≈12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Ninety-five dyads were randomized from four countries. Experimental arm superiority in communication-participation measurement of goal attainment was demonstrated (66.7% vs 49.1%, respectively, <i>p </i>= 0.006), and corroborated by post-study interviews.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Outcomes demonstrate the feasibility and initial efficacy of a person-centered telemedicine intervention for maximizing communication participation for mild-to-moderate PPA, providing a pathway for developing and implementing clinically meaningful interventions for Alzheimer's disease and related dementias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Primary progressive aphasia (PPA) negatively impacts communication participation.</li>\u0000 \u0000 <li>Communication Bridge-2 (CB2) is a telemedicine-delivered randomized controlled trial (RCT).</li>\u0000 \u0000 <li>Global recruitment of 95 PPA participant dyads into an RCT with low dropout.</li>\u0000 \u0000 <li>First international superiority trial for PPA using video chat shows efficacy.</li>\u0000 \u0000 <li>The study provides a model for rigorous non-pharmacologic trials for Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707445","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":"Targeting of phosphorylated tau at threonine 181 by a Qβ virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques","authors":"Nicole M. Maphis,&nbsp;Jonathan Hulse,&nbsp;Julianne Peabody,&nbsp;Somayeh Dadras,&nbsp;Madelin J Whelpley,&nbsp;Manas Kandath,&nbsp;Colin Wilson,&nbsp;Sasha Hobson,&nbsp;Jeff Thompson,&nbsp;Suttinee Poolsup,&nbsp;Danielle Beckman,&nbsp;Sean P Ott,&nbsp;Jennifer W. Watanabe,&nbsp;Jodie L. Usachenko,&nbsp;Koen K Van Rompay,&nbsp;John Morrison,&nbsp;Reed Selwyn,&nbsp;Gary Rosenberg,&nbsp;Janice Knoefel,&nbsp;Bryce Chackerian,&nbsp;Kiran Bhaskar","doi":"10.1002/alz.70101","DOIUrl":"https://doi.org/10.1002/alz.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Pathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer's disease (AD), and correlates with cognitive decline. A rapid surge in tau-targeted approaches via anti-sense oligonucleotides, active/passive immunotherapies suggests that targeting p-Tau is a viable strategy against tauopathies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHOD</h3>\u0000 \u0000 <p>We describe a multi-species validation of our previously described Qß virus-like particle (VLP)–based vaccine technology targeting phosphorylated tau on threonine 181 (pT181-Qß).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Two vaccine doses of pT181-Qß, without any adjuvants, elicited robust antibody responses in two different mouse models of tauopathy (PS19 and hTau) and rhesus macaques. In mouse models, vaccination reduced AT180+ hyperphosphorylated, Sarkosyl insoluble, Gallyas silver positive tau, inflammasomes/neuroinflammation, and improved recognition memory and motor function without inducing adverse T-cell activation. Anti-pT181 antibodies are reactive to pTau in human AD brains, engage pT181+ tau in human brain lysates, and are central nervous system bioavailable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results suggest the translational utility of pT181-Qß against tauopathies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Icosahedral display of phosphorylated tau at threonine 181 (pT181) Qß virus-like particle surface (“pT181-Qß” vaccine) induces a robust immune response in mice and in non-human primates (NHPs)</li>\u0000 \u0000 <li>pT181-Qß vaccination reduces pathological tau (pTau) and brain atrophy, and improves memory and motor function in PS19 and hTau mice.</li>\u0000 \u0000 <li>pT181-Qß vaccination–induced immunoglobulin Gs (IgGs) are safe, Th2 skewed (anti-inflammatory), specific to pTau in human AD brain, and efficiently engage pT181 in NHPs and human brain lysate.</li>\u0000 \u0000 <li>pT181⁺ tau in human plasma correlates with the neurofilament light in subjects with mild cognitive impairment (MCI)—suggesting the presence of pT181-Qß vaccine target in the early disease state.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707443","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":"Clinician type and care setting for treatment of Medicare beneficiaries with dementia","authors":"Donovan T. Maust,&nbsp;Rachel C. Davis,&nbsp;Ulrike Muench,&nbsp;Steven C. Marcus,&nbsp;Joanne Spetz","doi":"10.1002/alz.70102","DOIUrl":"https://doi.org/10.1002/alz.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Coordinating care for people living with dementia (PLWD) requires understanding which clinicians deliver care and the settings of that care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used the Medicare Carrier file to characterize the settings in which clinicians deliver care to PLWD, clinician types providing care, and whether clinicians record a dementia diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A total of 1,934,318 PLWD received care from 783,225 unique clinicians in 2019; PLWD saw a median of eight clinicians (interquartile range 5, 14). The most common settings were office (74.8% of PLWD), emergency room (63.9%), inpatient hospital (52.1%), and skilled nursing facility (37.1%). In addition, 87.0% of PLWD received care from a primary care physician, 62.9% from a nurse practitioner, and 33.1% from a physician assistant. Of the clinicians providing care, 2.4% are psychiatrists, 1.7% are neurologists, and 0.5% are geriatric subspecialists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Care for PLWD must be coordinated across multiple clinicians and settings, recognizing that few PLWD receive psychiatry, neurology, or geriatric subspecialty care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In 2019 the median Medicare beneficiary living with dementia saw eight different clinicians.</li>\u0000 \u0000 <li>Care of beneficiaries living with dementia is distributed across settings, with large percentages seen in each of the office, emergency room, inpatient hospital, and skilled nursing settings.</li>\u0000 \u0000 <li>Primary care physicians and nurse practitioners are the clinician types seen by the largest percentage of beneficiaries living with dementia.</li>\u0000 \u0000 <li>Geriatric subspecialist physicians account for less than 1% of the clinicians that provide care to beneficiaries living with dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707516","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":"Commonly prescribed multi-medication therapies exert sex-specific effects on Alzheimer's disease pathology and metabolomic profiles in AppNL-G-F mice: Implications for personalized therapeutics in aging","authors":"Francesca Eroli,&nbsp;Kristina Johnell,&nbsp;Zeynep Acararicin,&nbsp;Christina Tsagkogianni,&nbsp;Stefania Zerial,&nbsp;Saverio Lancia,&nbsp;Maria Latorre-Leal,&nbsp;Vilma Alanko,&nbsp;Sarah N. Hilmer,&nbsp;Anna Matton,&nbsp;Jonas W. Wastesson,&nbsp;Angel Cedazo-Minguez,&nbsp;Silvia Maioli","doi":"10.1002/alz.70081","DOIUrl":"https://doi.org/10.1002/alz.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Polypharmacy is common among older adults and people with dementia. Multi-medication therapy poses risks of harm but also targets comorbidities and risk factors associated with dementia, offering therapeutic potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We evaluated the effects of two polypharmacy regimens and monotherapies on male and female <i>App^NL-G-F</i> knock-in mice. We assessed functional, emotional, and cognitive outcomes;amyloid pathology; and serum metabolomics profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A combination of metoprolol, simvastatin, aspirin, paracetamol, and citalopram improved memory, reduced amyloid burden and neuroinflammation, and modulated AD-associated metabolomic signatures in male mice, with negligible effects in female mice. Substituting two cardiovascular drugs impacted emotional domains but worsened memory, predominantly in female mice. In males, monotherapies could not explain the combination effects, suggesting drug synergy, whereas in female mice, certain monotherapy effects were lost when combined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study uncovers the sex-specific effects of polypharmacy in an AD model, identifying mechanisms and biomarkers that can guide gender-specific use of medicines in dementia prevention and management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Two polypharmacy combinations show sex-specific effects on AD pathology and serum metabolomic profiles.</li>\u0000 \u0000 <li>Metoprolol+simvastatin+aspirin+paracetamol+citalopram improves memory and amyloid pathology in male mice.</li>\u0000 \u0000 <li>Replacing metoprolol and simvastatin with enalapril and atorvastatin eliminates benefits in male mice and impairs memory in female mice.</li>\u0000 \u0000 <li>Selected monotherapies produce sex-specific effects but only partially explain the outcomes of the combinations.</li>\u0000 \u0000 <li>Metabolomic pathways in serum indicate possible mechanisms and biomarkers for evaluating the effectiveness and safety of personalized therapies in aging and dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707314","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":"Heterogeneous brain abnormalities in subjective cognitive decline converge on a common network and their transcriptional signature","authors":"Huan Lan,&nbsp;Wenxiong Liu,&nbsp;Chao Zuo,&nbsp;Li Chen,&nbsp;Song Wang,&nbsp;Chunyan Luo,&nbsp;Weihong Kuang,&nbsp;Graham J Kemp,&nbsp;Su Lui,&nbsp;Xueling Suo,&nbsp;Qiyong Gong","doi":"10.1002/alz.70073","DOIUrl":"https://doi.org/10.1002/alz.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Subjective cognitive decline (SCD) is increasingly recognized as closely related to future Alzheimer's disease (AD). Numerous neuroimaging findings in SCD are inconsistent. We tested whether the various findings localize to a common brain network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using a novel coordinate network mapping approach, we delineated common brain damage networks that were functionally connected to reported neuroimaging findings. We then decoded these common networks using microscale transcriptomic and chemo-architectures and psychological processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We enrolled 45 studies comprising 2453 SCD patients and 3017 healthy controls. The identified SCD networks were largely localized in the somatosensory network (SMN) and default mode network (DMN). Both were robust to perturbations of analyzed parameters and in an independent validation dataset. Neurobiology correlation analyses identified some key biological pathways and neurotransmitters linked to these networks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings reconcile heterogeneous neuroimaging abnormalities in SCD and provide a richer neurobiological underpinning, which has implications for understanding patients with SCD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The heterogeneous neuroimaging findings on SCD were reconciled in a coordinate network mapping framework.</li>\u0000 \u0000 <li>The SCD-related functional network involves changes in the DMN, while the SCD-related structural network has changes mainly in primary sensory areas.</li>\u0000 \u0000 <li>The identified genes in the functional network were predominantly enriched in biological processes related to synaptic structure, calcium ion binding, and cellular metabolism.</li>\u0000 \u0000 <li>An ALE meta-analysis was conducted for comparison.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707377","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":"Cut-points and gray zones: The challenges of integrating Alzheimer's disease plasma biomarkers into clinical practice","authors":"Jemma Hazan,&nbsp;Kathy Y. Liu,&nbsp;Jeremy D. Isaacs,&nbsp;Robert Howard","doi":"10.1002/alz.70113","DOIUrl":"https://doi.org/10.1002/alz.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Plasma biomarkers for Alzheimer's disease (AD), such as plasma phosphorylated (p)-tau217, offer a more accessible means of testing for the presence of AD pathology compared to cerebrospinal fluid (CSF) or positron emission tomography (PET) methods. They can support diagnostic assessment and determine patient eligibility for treatment with amyloid beta–lowering drugs in community settings where access to CSF examination and amyloid-PET are limited. However, there are important challenges associated with interpreting and integrating plasma biomarker results in clinical practice. This article explores different approaches to interpreting plasma biomarker results in secondary care, important potential sources of uncertainty, and considerations for their clinical application.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma biomarkers such as phosphorylated tau-217 (p-tau217) offer a promising, accessible alternative to cerebrospinal fluid (CSF) and positron emission tomography (PET) for detecting Alzheimer's disease pathology, especially in settings with limited diagnostic resources.</li>\u0000 \u0000 <li>Clinical integration of plasma biomarker testing presents challenges, particularly in interpreting results. This includes uncertainties around intermediate results and their role in patient management.</li>\u0000 \u0000 <li>Clear frameworks and guidelines are essential to optimize the use of plasma biomarkers, supported by further research and education to ensure effective application in clinical practice.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707378","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":"Critical reflections on the impact of late-life social activity on dementia and mild cognitive impairment (MCI)","authors":"Sijia Liu,&nbsp;Jialao Ma","doi":"10.1002/alz.70108","DOIUrl":"https://doi.org/10.1002/alz.70108","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;We were particularly intrigued by the recent article by Chen et al., which is titled “Late-life social activity and subsequent risk of dementia and mild cognitive impairment.”&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This paper provides insightful opinions on the relationship between late-life social activity and dementia risks/mild cognitive impairment (MCI). Nonetheless, we would like to mention several limitations:&lt;/p&gt;&lt;p&gt;First, the study concentrates predominantly on measuring the quantity and frequency of social activities, without enough concerns for evaluating the quality or emotional importance of these interactions.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For instance, meeting with a social group may have far less significant perceived value than conversations with relatives or close friends. Such glaring differences between superficial and deep social experiences may constrain the explainability of results. Thus, we suggest using qualitative methods like structured interviews or validated scales to assess the emotional and cognitive impact of social activities.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This will enable a clearer understanding of how different types and qualities of social interactions affect cognitive health.&lt;/p&gt;&lt;p&gt;Second, the study provides only a brief description of the potential mechanisms whereby social activity may benefit cognitive health, like cognitive stimulation, stress reduction, and neurogenesis, without directly exploring these pathways in their research.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; This could raise concerns on the interpretability concerning the mechanisms through which social activities could help lessen or even prevent the onset of dementia. Hence, future studies may extend such links through the incorporation of biomarkers like neuroimaging, cortisol levels, or inflammatory markers to investigate the potential biological pathways inside. Moreover, despite the study controlled for loneliness and depression, these variables could themselves be bi-directionally related to social activities and dementia (e.g., depression may yield decrease in social activities and regarded as an early alarm of dementia).&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Such variables could be investigated as mediators/moderators so as to enhance the better understanding of the relationship between social engagement and the risk of dementia.&lt;/p&gt;&lt;p&gt;Third, this study appears to lack longitudinal data, which could potentially reflect the changes in social activities over time.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Because social activity patterns are very likely to be altered due to factors such as health, aging, and living environment, solely measuring social activity at baseline may not precisely capture the broader and dynamic relationship that it may have with dementia risk. For example, elderly people who were very socially active may, on account of some chronic diseases, become less involved, thereby increasing their chances of getting dementia. Furthermore, the shift toward greater use","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707380","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":"Amyloid PET predicts longitudinal functional and cognitive trajectories in a heterogeneous cohort","authors":"Kyan Younes,&nbsp;Emily Johns,&nbsp;Christina B. Young,&nbsp;Gabriel Kennedy,&nbsp;Shubhabrata Mukherjee,&nbsp;Hillary A. Vossler,&nbsp;Joseph Winer,&nbsp;Karly Cody,&nbsp;Victor W. Henderson,&nbsp;Kathleen L. Poston,&nbsp;Tobey J. Betthauser,&nbsp;Bill Bevis,&nbsp;William M. Brooks,&nbsp;Jeffrey M. Burns,&nbsp;Stephen A. Coombes,&nbsp;Charles DeCarli,&nbsp;Frank P. DiFilippo,&nbsp;Ranjan Duara,&nbsp;Audrey P. Fan,&nbsp;Laura E. Gibbons,&nbsp;Todd Golde,&nbsp;Sterling C. Johnson,&nbsp;Rebecca J. Lepping,&nbsp;James Leverenz,&nbsp;Sean McDougall,&nbsp;Emily Rogalski,&nbsp;Elizabeth Sanders,&nbsp;Joshua Pasaye,&nbsp;Jaiashre Sridhar,&nbsp;Andrew J. Saykin,&nbsp;Anjali Sridharan,&nbsp;Russell Swerdlow,&nbsp;Emily H. Trittschuh,&nbsp;David Vaillancourt,&nbsp;Eric Vidoni,&nbsp;Wei-en Wang,&nbsp;Jesse Mez,&nbsp;Timothy J. Hohman,&nbsp;Duygu Tosun,&nbsp;Sarah Biber,&nbsp;Walter A. Kukull,&nbsp;Paul K. Crane,&nbsp;Elizabeth C. Mormino","doi":"10.1002/alz.70075","DOIUrl":"https://doi.org/10.1002/alz.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Amyloid positron emission tomography (PET) is increasingly available for diagnosis of Alzheimer`s disease (AD); however, its practical implications in heterogenous cohorts are debated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Amyloid PET from 890 National Alzheimer`s Coordinating Center participants with up to 10 years post-PET follow up was analyzed. Cox proportional hazards and linear mixed models were used to investigate amyloid burden prediction of etiology and prospective functional status and cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Amyloid positivity was associated with progression from unimpaired to mild cognitive impairment and dementia. Amyloid burden in the unimpaired group was associated with lower initial memory levels and faster decline in memory, language, and global cognition. In the Impaired group, amyloid was associated with lower initial levels and faster decline for memory, language, executive function, and global cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Amyloid burden is an important prognostic marker in a clinically heterogeneous cohort. Future work is needed to establish the proportion of decline driven by AD versus non-AD processes in the context of mixed pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Our findings highlight the importance of amyloid positron emission tomography (PET) in heterogenous cohorts, including diverse demographics, clinical syndromes, and underlying etiologies.</li>\u0000 \u0000 <li>The results also provide evidence that higher amyloid levels were linked to functional progression from unimpaired cognition to mild cognitive impairment (MCI) and from MCI to dementia.</li>\u0000 \u0000 <li>In cognitively unimpaired individuals, higher amyloid burden was associated with poorer memory at baseline and subsequent declines in memory, language, and global cognition.</li>\u0000 \u0000 <li>Among individuals with cognitive impairment, amyloid burden was associated with worse initial memory, language, executive function, and global cognition, and faster declines over time.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707510","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}