Alzheimer's & Dementia最新文献

{"title":"Down syndrome versus dementia","authors":"Eden Rapp","doi":"10.1002/alz.70204","DOIUrl":"https://doi.org/10.1002/alz.70204","url":null,"abstract":"<p>Hi, my name is Eden Rapp. I am 28 years old, and I just graduated from a 3 year post-secondary program called Shepherds College in June 2024 in Wisconsin, where I studied Culinary Arts.</p><p>I have been a part of the Boston University Co-Research team for about two and a half years. We research different health problems for people with Down syndrome so that we can strive to be more independent. We just published a study about mental health.</p><p>If people with Down syndrome live long enough, they might get dementia. So far in my life, my experience with dementia comes from my grandmother. I learned some important things about dementia.</p><p>My grandmother had both not so good short- and long-term memory loss. Sometimes she could recall some things, but only in bits and pieces. Like she forgot who I was, and according to her, I was her servant that she had back in China. When my family was around, she would be nice to me, but when my family was doing other things, she treated me differently.</p><p>When you have dementia, it can be controlling at times and can change a person. My grandmother hardly let anyone come near her; only four people made her feel safe and secure: my mom, my dad, my uncle, and her dog. It made me feel invisible.</p><p>Sometimes, having dementia is like playing telephone, where you say something one way, but then something completely different comes out of your mouth, and then it goes away like lightning. So, my grandmother had that problem, so we found that writing on a sticky note was very helpful, so if we didn't want to repeat ourselves and get annoyed, we would refer to the sticky note. That wouldn't work sometimes, and I would need to change the subject and calm her down by playing two musicals that she loved, The Sound of Music and My Fair Lady.</p><p>Sometimes she would leave the house and wander around until she made it back home successfully. For example, when we were at my great aunt's house in Connecticut, my grandmother forgot where she was, and she did not feel safe. She knew she wasn't around her safety net, so she got up and wandered away. By the time I woke up, my mom and my great uncle found her in the hospital after she was picked up by the police. So, sometimes being disoriented can be dangerous for someone with dementia. So, finding and using appropriate safety nets is really important to help someone who can easily be disoriented.</p><p>Even though she had dementia, there were still ways she was true to herself. Her love for music played a big part in her life, and at the end of her life, it kept her connected to me. The only time that she would say my real name and not call me her servant was when I was practicing piano or when my brother would practice singing or trumpet.</p><p>For me personally, it was hard to love and forgive my grandmother, but then I learned something that helped me change my mind. My mom taught me that “When you have dementia, you are not your true self, the true self is jus","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323569","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":"Lifespan exposures to rural–urban conditions and later-life cognitive function","authors":"Lingzhi Chu,&nbsp;Yingyan Wu,&nbsp;Heidi Karjalainen,&nbsp;Olivia E. Atherton","doi":"10.1002/alz.70267","DOIUrl":"https://doi.org/10.1002/alz.70267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Limited research exists on life-course rural–urban residence and cognitive functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This study examines associations between rural–urban residence during childhood, adulthood, residential mobility (childhood to adulthood), and later-life cognitive outcomes among U.S. adults ≥65 years of age (<i>N</i> = 3073) from the Health and Retirement Study-Harmonized Cognitive Assessment Protocol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Linear and logistic regression showed that childhood rural residence was associated with lower memory (standardized beta (β) = –1.68, 95% Confidence Interval (CI) [–2.39, –0.97]), executive function (β = –1.20, 95% CI [–1.84, –0.55]), and language fluency (β = –0.86, 95% CI [–1.64, –0.08]). Individuals living in rural areas in childhood had a higher risk for mild cognitive impairment (MCI; odds ratio [OR] = 1.31, 95% CI [1.02, 1.69]) and dementia/MCI (OR = 1.30, 95% CI [1.04, 1.62]). Compared to lifelong urban residents; residents who lived in rural areas during childhood and/or adulthood had lower cognitive function and a higher risk of MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Rural residence throughout the lifespan, especially during childhood, is linked to poorer later-life cognitive outcomes, underscoring the need for early targeted health care interventions to address rural–urban disparities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Few studies have examined the timing of rural residence on cognitive health.</li>\u0000 \u0000 <li>Rural residence across the lifespan is associated with lower cognitive function.</li>\u0000 \u0000 <li>Childhood rurality is particularly associated with lower cognitive function.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323592","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":"Longitudinal associations between self-reported exercise levels and cognition in ADAD","authors":"Kelsey R. Sewell,&nbsp;James D. Doecke,&nbsp;Ralph N. Martins,&nbsp;Stephanie R. Rainey-Smith,&nbsp;Jeremiah Peiffer,&nbsp;Samantha L. Gardener,&nbsp;Hamid R. Sohrabi,&nbsp;Kirk I. Erickson,&nbsp;Belinda M. Brown,&nbsp;The Dominantly Inherited Alzheimer Network (DIAN)","doi":"10.1002/alz.70383","DOIUrl":"https://doi.org/10.1002/alz.70383","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants (<i>n </i>= 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not moderate these associations. In the years preceding first cognitive symptoms or last follow-up visit, mutation carriers showed a decline in their exercise engagement compared to mutation non-carriers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Self-reported exercise is associated with preserved cognitive function in those with ADAD mutations; however, AD-related pathways may influence the level of engagement in exercise prior to cognitive symptom onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Greater weekly exercise predicts slower cognitive decline in ADAD mutation carriers.</li>\u0000 \u0000 <li>These associations varied dependent on closeness to estimated symptom onset.</li>\u0000 \u0000 <li>These associations were not moderated by sex.</li>\u0000 \u0000 <li>Weekly exercise declined in ADAD mutation carriers compared to non-carriers.</li>\u0000 \u0000 <li>Results may suggest a bidirectional relationship between exercise and AD risk.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315025","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":"The dynamics of cognitive decline toward Alzheimer's disease progression: Results from ADSP-PHC's harmonized cognitive composites","authors":"Kaidi Kang,&nbsp;Panpan Zhang,&nbsp;Logan Dumitrescu,&nbsp;Shubhabrata Mukherjee,&nbsp;Michael L. Lee,&nbsp;Seo-Eun Choi,&nbsp;Emily H. Trittschuh,&nbsp;Jesse Mez,&nbsp;Andrew J. Saykin,&nbsp;Katherine A. Gifford,&nbsp;Rachel F. Buckley,&nbsp;Xiaoting Gao,&nbsp;Jianing Di,&nbsp;Paul K. Crane,&nbsp;Timothy J. Hohman,&nbsp;Dandan Liu","doi":"10.1002/alz.70335","DOIUrl":"https://doi.org/10.1002/alz.70335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Accurately assessing the temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presents controversial conclusions likely due to the use of a single cohort and different analytical strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Harmonized composite cognitive measures in memory, language, and executive functions from 13 cohorts in the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) were used. A double anchoring events–based sigmoidal mixed model was developed using time to incident AD diagnosis as the time scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In general, decline in memory occurred before decline in language, followed by decline in executive function. This temporal order generally persisted within each subgroup of apolipoprotein E ε4 carrier status, sex, and race/ethnicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study demonstrated the use of harmonized data across multiple cohorts to characterize the temporal order of cognitive decline along AD progression. Using time to incident AD diagnosis as the time scale can enhance research reproducibility and clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium's harmonized composite cognitive measures from 13 cohort studies fitted with a novel double anchoring event-based sigmoidal mixed model reveal the following temporal order of cognitive decline toward AD progression: memory, language, and executive function.</li>\u0000 \u0000 <li>If only investigated using individual cohort studies, the temporal order of cognitive decline would vary due to the underlying heterogeneities across studies.</li>\u0000 \u0000 <li>This temporal order generally persisted within each subgroup of apolipoprotein E ε4 carrier status, sex, and race/ethnicity.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323578","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":"Down syndrome with Alzheimer's disease brains have increased iron and associated lipid peroxidation consistent with ferroptosis","authors":"Max A. Thorwald,&nbsp;Jose A. Godoy-Lugo,&nbsp;Elizabeth Kerstiens,&nbsp;Gilberto Garcia,&nbsp;Minhoo Kim,&nbsp;Sarah J. Shemtov,&nbsp;Justine Silva,&nbsp;Salma Durra,&nbsp;Peggy A. O'Day,&nbsp;Wendy J. Mack,&nbsp;Annie Hiniker,&nbsp;Marc Vermulst,&nbsp;Bérénice A. Benayoun,&nbsp;Ryo Higuchi-Sanabria,&nbsp;Henry Jay Forman,&nbsp;Elizabeth Head,&nbsp;Caleb E. Finch","doi":"10.1002/alz.70322","DOIUrl":"https://doi.org/10.1002/alz.70322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cerebral microbleeds (MBs) are associated with sporadic Alzheimer's disease (AD) and Down syndrome with AD (DSAD). Higher MB iron may cause iron-mediated lipid peroxidation. We hypothesize that amyloid deposition is linked to MB iron and that amyloid precursor protein (APP) triplication increases iron load and lipid peroxidation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Prefrontal cortex and cerebellum of cognitively normal control (CTL), AD, and DSAD ApoE3,3 carriers were examined for proteins that mediated iron metabolism, antioxidant response, and amyloid processing in lipid rafts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Iron was twofold higher in DSAD than in CTL and AD. Iron storage proteins and lipid peroxidation were increased in the prefrontal cortex. The glutathione synthesis protein GCLM was decreased by 50% in both AD and DSAD. Activity of lipid raft GPx4, responsible for membrane repair, was decreased by at least 30% in AD and DSAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>DSAD shows greater lipid peroxidation than AD, consistent with greater MBs and iron load.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>DSAD has increased ferroptotic-related changes compared to sporadic AD.</li>\u0000 \u0000 <li>Lipid rafts that process APP have a loss of protective antioxidant enzymes.</li>\u0000 \u0000 <li>Partial and mosaic trisomy lowers the amyloid and iron burden.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315024","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":"Competency-based training boosts dementia knowledge and skills in home care workers","authors":"Jarmin Yeh,&nbsp;Matthew Beld,&nbsp;Brittney Pond,&nbsp;Melinda Neri,&nbsp;Andrea Garcia,&nbsp;Juliana Mata-Pacheco,&nbsp;Juvenal Mauricio,&nbsp;Moraima Castanenda,&nbsp;Corinne Eldridge,&nbsp;Suzanna Martinez","doi":"10.1002/alz.70323","DOIUrl":"https://doi.org/10.1002/alz.70323","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The rising prevalence of Alzheimer's disease and related dementias (ADRD) in California's aging population necessitates a well-trained dementia care workforce.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This study evaluated a multi-week, competency-based, online training for caregivers in California's Medicaid-funded In-Home Supportive Services (IHSS) program. Using a quasi-experimental design, we assessed caregivers’ dementia knowledge, self-efficacy, distress, depression, and care recipients’ healthcare use before and after the intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The training significantly improved caregivers’ dementia knowledge and self-efficacy but did not reduce caregivers’ distress and depression, nor decrease care recipients’ emergency room visits and hospitalizations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The findings highlight the value of specialized dementia training in enhancing caregiver knowledge and skills, which could be implemented outside California. Clinical implications include bolstering caregiver well-being to improve the quality of their support of care recipients with cognitive impairment. Policy implications include expanding access to training programs and bolstering workforce development initiatives that improve caregiver and care recipient outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Multiweek online training improved home care workers’ dementia caregiving skills.</li>\u0000 \u0000 <li>Home care workers’ dementia knowledge improved significantly post-training.</li>\u0000 \u0000 <li>Self-efficacy to manage care recipients’ dementia symptoms improved significantly.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323593","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":"Increased activity of Piezo1 channel in red blood cells is associated with Alzheimer's disease-related dementia","authors":"Valeriia Sitnikova,&nbsp;Dilyara Nurkhametova,&nbsp;Nicoletta Braidotti,&nbsp;Catalin D. Ciubotaru,&nbsp;Luca Giudice,&nbsp;Ulla Impola,&nbsp;Sari Kärkkäinen,&nbsp;Juho Kalapudas,&nbsp;Elina Penttilä,&nbsp;Heikki Löppönen,&nbsp;Ilkka Fagerlund,&nbsp;Katja M. Kanninen,&nbsp;Henrik Zetterberg,&nbsp;Tarja Kokkola,&nbsp;Saara Laitinen,&nbsp;Anne Koivisto,&nbsp;Dan Cojoc,&nbsp;Rashid Giniatullin,&nbsp;Tarja M. Malm","doi":"10.1002/alz.70368","DOIUrl":"https://doi.org/10.1002/alz.70368","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Red blood cells (RBCs) are crucial for oxygen delivery to active tissues and endure significant mechanical forces in the microcirculatory bed. The enrichment of mechanosensitive Piezo1 channels, linked to the cytoskeleton, aids RBCs in navigating the narrow capillaries. In Alzheimer's disease (AD), impaired brain microcirculation may necessitate enhanced Piezo1 function in RBCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>With micropipette aspiration and flow cytometry technics, we evaluated, using the specific Piezo1 agonist Yoda1, AD-related alterations in the biomechanical properties of RBCs from cognitively healthy patients (HC) and individuals with mild cognitive impairment (MCI) and AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We show that beta-amyloid (Aβ) peptides alter the biomechanical properties of RBCs. We observed significantly higher Yoda1-induced calcium responses in RBCs in individuals with MCI and AD compared to RBCs from age-matched HC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>Our data suggest that Yoda1-induced Ca²⁺ flux through Piezo1 channel emerges as a measurable indicator associated with and improves the detection of AD-related dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Piezo1 channels aid the navigation of red blood cells (RBCs) through narrow capillaries.</li>\u0000 \u0000 <li>Alzheimer's disease (AD) patients show increased Yoda1-induced activation of Piezo1 in RBCs.</li>\u0000 \u0000 <li>Incorporation of Yoda1-induced Piezo1 readouts improved the detection of AD-related dementia.</li>\u0000 \u0000 <li>Investigating Yoda1-induced Piezo1 activity associated with early AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315357","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":"The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease","authors":"Annibale Antonioni,&nbsp;Alessandro Martorana,&nbsp;Emiliano Santarnecchi,&nbsp;Harald Hampel,&nbsp;Giacomo Koch","doi":"10.1002/alz.70337","DOIUrl":"https://doi.org/10.1002/alz.70337","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS), are promising candidate therapeutics for Alzheimer's disease (AD). We review the evidence supporting the fundamental mechanisms of action of rTMS treatments in AD. rTMS exerts profound effects at different neurobiological and systems neurophysiological levels. By engaging distinct pre- and postsynaptic structures within the stimulated neural network, it directly or indirectly influences various cellular and molecular components. In AD, rTMS influences synaptic plasticity, inducing lasting structural changes and broad reorganization of functional and structural connectivity at the macroscale level. Importantly, it modulates neurotransmitter circuits characteristically disrupted in AD and restores the excitation/inhibition balance by targeting glutamatergic and γ-aminobutyric acid (GABA)ergic pathways. Moreover, rTMS increases neurotrophic factors, counteracts amyloid and tau accumulation, and mitigates neuroinflammation by reducing microglial activation and pro-inflammatory cytokines release. Therefore, maturing preclinical evidence could guide future precision medicine therapeutic strategies based on personalized NIBS in AD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS), are promising candidate therapeutics for Alzheimer's disease (AD).</li>\u0000 \u0000 <li>rTMS modulates neuroplasticity, neurotransmission, and neuroinflammation.</li>\u0000 \u0000 <li>Preclinical research shows disease-specific neurobiological effects of rTMS in AD.</li>\u0000 \u0000 <li>Promising data from AD patients suggest the translatability of animal model results.</li>\u0000 \u0000 <li>Preclinical data may guide precision medicine strategies through personalized NIBS.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308785","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":"Alpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease","authors":"Alexander Maximilian Bernhardt,&nbsp;Íñigo Rodríguez-Baz,&nbsp;Iban Aldecoa,&nbsp;Javier Arranz,&nbsp;José Enrique Arriola-Infante,&nbsp;Lucia Maure-Blesa,&nbsp;Maria Carmona-Iragui,&nbsp;Sebastian Longen,&nbsp;Svenja Verena Trossbach,&nbsp;Armin Giese,&nbsp;Torsten Matthias,&nbsp;Bessy Benejam,&nbsp;Laura Videla,&nbsp;Laura del Hoyo Soriano,&nbsp;Isabel Barroeta,&nbsp;Aída Sanjuan,&nbsp;Susana Fernández,&nbsp;Lídia Vaqué-Alcázar,&nbsp;Mateus Rozalem Aranha,&nbsp;Alejandra O. Morcillo-Nieto,&nbsp;Georg Nübling,&nbsp;Olivia Wagemann,&nbsp;Anna Stockbauer,&nbsp;Mireia Tondo,&nbsp;Alexandre Bejanin,&nbsp;Alberto Lleó,&nbsp;Daniel Alcolea,&nbsp;Laura Molina-Porcel,&nbsp;Juan Fortea,&nbsp;Johannes Levin","doi":"10.1002/alz.70342","DOIUrl":"https://doi.org/10.1002/alz.70342","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alpha-synuclein (αSyn) seed amplification assay (SAA) enables in vivo study of αSyn but remains underexplored in Down syndrome-associated Alzheimer's disease (DSAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed αSyn-SAA in cerebrospinal fluid (CSF) from 270 adults with Down syndrome, from the Down Alzheimer Barcelona Neuroimaging Initiative and from the AD21 cohort from the Department of Neurology at the University Hospital, Ludwig Maximilian University of Munich, Germany. Neuropathological examinations were conducted in 19 brain donors (five with <i>ante mortem</i> CSF). Participants were classified as asymptomatic or symptomatic (prodromal/dementia) Alzheimer's disease (AD). CSF Aβ1-42/1-40, CSF and plasma p-Tau181, and neurofilament light chain (NfL) levels were measured. Neuropathological evaluations assessed AD neuropathological changes and Lewy body pathology (LBP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>ΑSyn-SAA was positive in 9.2% of cases, independent of age or cognitive status. Symptomatic αSyn-positive cases exhibited higher plasma NfL levels than αSyn-negative cases (31 vs 21 pg/mL, <i>p</i> = 0.027). LBP was observed in 47% of necropsies. The individual with severe neocortical LBP was αSyn-SAA-positive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings highlight LBP prevalence in DSAD but suggest current SAA may fail to detect limited αSyn deposition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>αSyn-SAA positivity in DSAD is 9.2%, similar to ADAD but lower than sporadic AD.</li>\u0000 \u0000 <li>Misfolded αSyn was detectable from early ages in individuals with DS.</li>\u0000 \u0000 <li>Positivity rates did not vary with age or clinical status in DS.</li>\u0000 \u0000 <li>Plasma NfL levels are higher in symptomatic αSyn-SAA positive versus negative cases.</li>\u0000 \u0000 <li>CSF αSyn seeding activity was associated with high neocortical LBP at necropsy.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308807","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":"Translation and cultural adaptation of tools to assess diverse Asian American and Asian Canadian subgroups: The Asian Cohort for Alzheimer's Disease (ACAD) Study","authors":"Haeok Lee,&nbsp;Marian Tzuang,&nbsp;Tiffany W. Chow,&nbsp;Younhee Kang,&nbsp;Boon Lead Tee,&nbsp;Clara Li,&nbsp;Eleanor Lam,&nbsp;Yian Gu,&nbsp;SangA Lee,&nbsp;Pei-Chuan Ho,&nbsp;Guerry Peavy,&nbsp;Eun Hyun Seo,&nbsp;Kyungmin Kim,&nbsp;Binh Tran,&nbsp;Wonjeong Chae,&nbsp;Dat Nguyen,&nbsp;Namkhue Vo,&nbsp;Deanna Dang,&nbsp;Jessica Spat-Lemus,&nbsp;Yun-Beom Choi,&nbsp;Howard Feldman,&nbsp;Gyungah R. Jun,&nbsp;Li-San Wang,&nbsp;Wai Haung Yu,&nbsp;Van Ta M. Park,&nbsp;The Asian Cohort for Alzheimer's Disease Study","doi":"10.1002/alz.70311","DOIUrl":"https://doi.org/10.1002/alz.70311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The availability of sociocultural and language-appropriate study materials and instruments is critical for the assessment of cognitive function in people from diverse backgrounds. This report describes the translations and cultural adaptations of study materials for the Asian Cohort for Alzheimer's Disease (ACAD) study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed translations and cultural adaptations in accordance with the World Health Organization (WHO) translation guidelines to ensure reliable, complete, and culturally appropriate translations from English to the specified Asian languages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We developed Asian language versions of the ACAD documents (consent, data collection packet, and community and social media outreach materials) reflecting the sociocultural backgrounds of the ACAD target population (i.e., older Asian adults)</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The multistep translation process accounting for distinctive Asian sociocultural and language backgrounds provides an important guideline for Alzheimer's disease and related dementias (ADRD) researchers to promote health literacy and research with underrepresented Asian American and Canadian adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Asian American and Asian Canadian older adults are the fastest-growing populations.</li>\u0000 \u0000 <li>A lack of linguistically and culturally appropriate cognitive assessment tools creates barriers for quality healthcare and clinical research.</li>\u0000 \u0000 <li>We report the translations and cultural adaptations of the Asian Cohort for Alzheimer's Disease (ACAD) study materials into Chinese, Korean, and Vietnamese.</li>\u0000 \u0000 <li>This translation methodology should be extended to Asian Indians, Filipinos, and other Asian American or Asian Canadian populations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308980","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}