David N. Soleimani-Meigooni, Stefania Pezzoli, Ganna Blazhenets, Renaud La Joie, Zoe Lin, Carol L. Soppe, Derek R. Johnson, Mary Ellen I. Koran, Jonathan E. McConathy, Ilya M. Nasrallah, Maria Rosana Ponisio, Jeremy A. Tanner, Victor L. Villemagne, Charles C. Windon, Michael Zeineh, Sarah Biber, Walter A. Kukull, Heather O'Connell, Daniel J. Peterson, Elizabeth C. Mormino, Sterling C. Johnson, Gil D. Rabinovici, for the LEADS Consortium, The PREVENT-AD Research Group, Alzheimer's Disease Neuroimaging Initiative
{"title":"Calibration of multisite raters for prospective visual reads of amyloid PET scans","authors":"David N. Soleimani-Meigooni, Stefania Pezzoli, Ganna Blazhenets, Renaud La Joie, Zoe Lin, Carol L. Soppe, Derek R. Johnson, Mary Ellen I. Koran, Jonathan E. McConathy, Ilya M. Nasrallah, Maria Rosana Ponisio, Jeremy A. Tanner, Victor L. Villemagne, Charles C. Windon, Michael Zeineh, Sarah Biber, Walter A. Kukull, Heather O'Connell, Daniel J. Peterson, Elizabeth C. Mormino, Sterling C. Johnson, Gil D. Rabinovici, for the LEADS Consortium, The PREVENT-AD Research Group, Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70732","DOIUrl":"10.1002/alz.70732","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>In multicenter Alzheimer's disease studies, amyloid positron emission tomography (PET) visual reads are typically performed centrally by a few experts. Incorporating a broader reader network enhances scalability and generalizability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Ten neuroimaging experts from eight Alzheimer's Disease Research Centers (ADRCs) visually read 180 amyloid PET scans (30 scans and 15 duplicate scans for each of four tracers, imaged across a wide variety of scanners), using preferred reading software without anatomical imaging or quantitation. Scans were classified as elevated or non-elevated per tracer-specific criteria. Inter- and intra-rater agreement was assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Inter-rater agreement was substantial (Fleiss’ <i>κ</i> = 0.78), with full consensus on 69% of scans. Inter-rater reliability was substantial to perfect across tracers (Fleiss’ <i>κ</i> = 0.70–0.87). Intra-rater agreement was substantial to perfect (Cohen's <i>κ </i>= 0.79-1). Scans with intermediate (10–40 Centiloid) quantitation had lower reader agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>A multicenter expert network achieved substantial agreement classifying amyloid PET scans. These scans provide a standard for reader training and reliability assurance in future studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Calibration methods ensure reliable amyloid positron emission tomography (PET) visual reads across multiple raters.</li>\u0000 \u0000 <li>Substantial agreement is possible across readers using their preferred tools.</li>\u0000 \u0000 <li>Agreement is also substantial regardless of the amyloid PET tracer used.</li>\u0000 \u0000 <li>Scans with intermediate (10–40 Centiloid) quantitation have lower reader agreement.</li>\u0000 \u0000 <li>The calibration set will become a training tool for amyloid PET visual read studies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194519","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}
Teodora Z. Markova, Corrina S. Fonseca, Claire J. Ciampa, Alice Murphy, Susan Landau, Theresa M. Harrison, Anne S. Berry, for the Alzheimer's Disease Neuroimaging Initiative
{"title":"Defining the contributions of tau pathology in the amygdala to increasing depressive symptoms in aging","authors":"Teodora Z. Markova, Corrina S. Fonseca, Claire J. Ciampa, Alice Murphy, Susan Landau, Theresa M. Harrison, Anne S. Berry, for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70740","DOIUrl":"10.1002/alz.70740","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Amygdala tau accumulates in cognitively normal individuals and may contribute to neuropsychiatric changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we investigated relationships among cross-sectional and longitudinal tau ([18F]Flortaucipir [FTP] positron emission tomography), changes in depressive symptoms and memory, and amyloid beta and apolipoprotein E (<i>APOE)</i> ε4 status. We report secondary analyses from the Berkeley Aging Cohort Study (BACS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Longitudinal increases in depressive symptoms were associated with higher baseline FTP and increasing FTP in the amygdala. Relationships between FTP and depressive symptoms were strongest in <i>APOE</i> ε4 carriers, with moderation effects replicating in BACS. Entorhinal FTP did not show associations with depressive symptoms beyond variance explained by the amygdala but showed some specific associations with memory decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings indicate the strongest coupling between tau accumulation and depressive symptoms in <i>APOE</i> ε4 carriers and reinforce the importance of amygdala tau in understanding neuropsychiatric changes in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>There is a lack of research focused on the role of tau in the amygdala in cognitively normal older adults.</li>\u0000 \u0000 <li>Amygdala tau is related to both worsening depressive symptoms and declining memory performance.</li>\u0000 \u0000 <li><i>APOE</i> ε4 carriers seem to drive positive tau-depressive symptom associations.</li>\u0000 \u0000 <li>Focusing on the amygdala tau is useful for understanding neuropsychiatric trajectories in cognitively unimpaired older adults.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194516","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}
Yasminka A. Jakubek, Aaron P. Smith, Xiaoyan I. Leng, Megan E. Hall, Daniel Ezzat, Yash Pershad, Jason M. Collins, Md Mesbah Uddin, David W. Fardo, Pradeep Natarajan, Alexander G. Bick, Jacob O. Kitzman, Michael C. Honigberg, Kathleen M. Hayden, JoAnn E. Manson, Siddhartha Jaiswal, Eric A. Whitsel, Alexander P. Reiner
{"title":"Clonal hematopoiesis of indeterminate potential and the risk of cognitive impairment in the Women's Health Initiative Memory Study","authors":"Yasminka A. Jakubek, Aaron P. Smith, Xiaoyan I. Leng, Megan E. Hall, Daniel Ezzat, Yash Pershad, Jason M. Collins, Md Mesbah Uddin, David W. Fardo, Pradeep Natarajan, Alexander G. Bick, Jacob O. Kitzman, Michael C. Honigberg, Kathleen M. Hayden, JoAnn E. Manson, Siddhartha Jaiswal, Eric A. Whitsel, Alexander P. Reiner","doi":"10.1002/alz.70737","DOIUrl":"10.1002/alz.70737","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF ≥ 8%) was associated with a lower incidence of adjudicated probable dementia (hazard ratio = 0.62 [95% confidence interval = 0.41 to 0.94], <i>p </i>= 0.025), while the association with the composite outcome MCI/probable dementia was weaker and overlapped 1.0.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The association of CHIP with lower risk of cognitive impairment in postmenopausal women may be dependent on VAF and impairment severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The WHIMS comprises ∼5000 postmenopausal women, followed for up to 25 years.</li>\u0000 \u0000 <li>CHIP was associated with reduced risk of adjudicated probable dementia in WHIMS.</li>\u0000 \u0000 <li>Large CHIP clones (> 8% VAF), but not small clones (<8% VAF), showed an association.</li>\u0000 \u0000 <li>CHIP was not associated with MCI in the WHIMS cohort.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Tenascin-R aggravates Aβ production in the perforant pathway by regulating Nav1.6 activity in APP/PS1 mice\"","authors":"","doi":"10.1002/alz.70759","DOIUrl":"10.1002/alz.70759","url":null,"abstract":"<p>Wang B, Wang ZX, Lv LM, et al. Tenascin-R aggravates Aβ production in the perforant pathway by regulating Nav1.6 activity in APP/PS1 mice. <i>Alzheimers Dement</i>. 2025;21(9):e70633. 10.1002/alz.70633</p><p>One of the corresponding authors was listed as “Li Shao” in the article. The correct name should be Shao Li, with “Shao” as the first name and “Li” as the family name.</p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189482","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}
Yousaf Abughofah, Shannon L. Risacher, Frederick W. Unverzagt, Martin R. Farlow, Liana G Apostolova, Jared R. Brosch, David G. Clark, Sunu Mathew, Sujuan Gao, Selena Wang, Sophia Wang, Andrew J. Saykin
{"title":"The Cognitive Change Index in the Alzheimer's Disease Research Center setting: Self- and informant-ratings for perceived cognitive decline","authors":"Yousaf Abughofah, Shannon L. Risacher, Frederick W. Unverzagt, Martin R. Farlow, Liana G Apostolova, Jared R. Brosch, David G. Clark, Sunu Mathew, Sujuan Gao, Selena Wang, Sophia Wang, Andrew J. Saykin","doi":"10.1002/alz.70754","DOIUrl":"10.1002/alz.70754","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Cognitive Change Index (CCI) is a brief questionnaire that assesses self and informant perceptions regarding cognitive function. We examined the ability of the CCI to distinguish between cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI) or Alzheimer's disease (AD) dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>485 individuals from the Indiana Alzheimer's Disease Research Center (IADRC) and their study partners completed 20-item self and informant versions of the CCI. Receiver operator characteristic (ROC) curves were analyzed to assess differentiation between CU and those with impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>High area under the ROC curve (AUC) values were obtained when using the self and informant CCI forms to distinguish CU individuals from those with impairment, with AUC values of 0.803 (95% confidence interval [CI] = 0.761–0.844) and 0.914 (95% CI = 0.886–0.942) for the self and informant forms, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The CCI can serve as a useful screening instrument in the context of a multimodal assessment strategy for MCI and dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Novel research that uses the Cognitive Change Index (CCI) for dementia screening.</li>\u0000 \u0000 <li>Our findings suggest that CCI can distinguish those with dementia compared to those without.</li>\u0000 \u0000 <li>These findings can be correlated to other screening instruments.</li>\u0000 \u0000 <li>Results could see the CCI play a role in early Alzheimer's disease (AD) screening and diagnosis.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70754","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194652","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}
Yiwen Chen, Meng Li, Jing Li, Pengcheng Liang, Zhenyu Cheng, Na Wang, Xinyue Zhang, Yuanyuan Wang, Nan Zhang, Yena Che, Wenwen Gao, Lingfei Guo, Changhu Liang
{"title":"Associations of neurodegenerative proteins with brain iron deposition and cognition in cerebral small vessel disease: a quantitative susceptibility mapping and plasma biomarker study","authors":"Yiwen Chen, Meng Li, Jing Li, Pengcheng Liang, Zhenyu Cheng, Na Wang, Xinyue Zhang, Yuanyuan Wang, Nan Zhang, Yena Che, Wenwen Gao, Lingfei Guo, Changhu Liang","doi":"10.1002/alz.70710","DOIUrl":"10.1002/alz.70710","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cerebral small vessel disease (CSVD) is a common neurological disorder with limited pathology on conventional magnetic resonance imaging. This study uses quantitative susceptibility mapping (QSM) to investigate links among brain iron, plasma neurodegenerative proteins, and cognition in CSVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This study enrolled 319 CSVD patients, grouped into CSVD-M and CSVD-S. Plasma proteins were measured in 178 participants, with 80 being followed up after 2 years. QSM-based voxel-wise analysis assessed brain iron, CSVD severity, and protein correlations. A cross-lagged panel model was used to analyze the temporal association between plasma protein levels and brain iron levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In CSVD-S, elevated QSM values in the right Rolandic operculum/superior temporal gyrus negatively correlated with plasma Aβ42 and executive function. Aβ42 also negatively correlated with QSM in cortical regions, tied to episodic memory decline. Higher baseline Aβ40 predicted increased QSM in the left putamen at follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma Aβ42 and Aβ40 may drive brain iron deposition and cognitive impairment in CSVD, serving as potential early biomarkers for disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>QSM reveals brain iron links to Aβ42, cognition in CSVD.</li>\u0000 \u0000 <li>Plasma Aβ42 correlates with iron in motor and frontal areas.</li>\u0000 \u0000 <li>High Aβ40 predicts putamen iron increase in CSVD follow-up.</li>\u0000 \u0000 <li>Iron deposition is tied to executive, memory deficits in CSVD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188466","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}
Sylvia Villeneuve, Judes Poirier, John C. S. Breitner, Jennifer Tremblay-Mercier, Jordana Remz, Jean-Michel Raoult, Yara Yakoub, Jonathan Gallego-Rudolf, Ting Qiu, Alfonso Fajardo Valdez, Bery Mohammediyan, Mohammadali Javanray, Amelie Metz, Safa Sanami, Valentin Ourry, Alfie Wearn, Alexandre Pastor-Bernier, Manon Edde, Julie Gonneaud, Cherie Strikwerda-Brown, Christine L. Tardif, Claudine J. Gauthier, Maxime Descoteaux, Mahsa Dadar, Étienne Vachon-Presseau, Andrée-Ann Baril, Simon Ducharme, Maxime Montembeault, Maiya R. Geddes, Jean-Paul Soucy, Natasha Rajah, Robert Laforce, Christian Bocti, Christos Davatzikos, Lune Bellec, Pedro Rosa-Neto, Sylvain Baillet, Alan C. Evans, D. Louis Collins, M. Mallar Chakravarty, Kaj Blennow, Henrik Zetterberg, R. Nathan Spreng, Alexa Pichet Binette, the PREVENT-AD Research Group
{"title":"The PREVENT-AD cohort: Accelerating Alzheimer's disease research and treatment in Canada and beyond","authors":"Sylvia Villeneuve, Judes Poirier, John C. S. Breitner, Jennifer Tremblay-Mercier, Jordana Remz, Jean-Michel Raoult, Yara Yakoub, Jonathan Gallego-Rudolf, Ting Qiu, Alfonso Fajardo Valdez, Bery Mohammediyan, Mohammadali Javanray, Amelie Metz, Safa Sanami, Valentin Ourry, Alfie Wearn, Alexandre Pastor-Bernier, Manon Edde, Julie Gonneaud, Cherie Strikwerda-Brown, Christine L. Tardif, Claudine J. Gauthier, Maxime Descoteaux, Mahsa Dadar, Étienne Vachon-Presseau, Andrée-Ann Baril, Simon Ducharme, Maxime Montembeault, Maiya R. Geddes, Jean-Paul Soucy, Natasha Rajah, Robert Laforce, Christian Bocti, Christos Davatzikos, Lune Bellec, Pedro Rosa-Neto, Sylvain Baillet, Alan C. Evans, D. Louis Collins, M. Mallar Chakravarty, Kaj Blennow, Henrik Zetterberg, R. Nathan Spreng, Alexa Pichet Binette, the PREVENT-AD Research Group","doi":"10.1002/alz.70653","DOIUrl":"10.1002/alz.70653","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is an investigator-driven study that was created in 2011 and enrolled cognitively normal older adults with a family history of sporadic AD. Participants are deeply phenotyped and have now been followed annually for more than 12 years (median follow-up 8.0 years, SD 3.1). Multimodal magnetic resonance imaging (MRI), genetic, neurosensory, clinical, cerebrospinal fluid, and cognitive data collected until 2017 on 348 participants who agreed to open sharing with the neuroscience community were already available. We now share a new release including 6 years of additional follow-up cognitive data, and additional MRI follow-ups, clinical progression, new longitudinal behavioral and lifestyle measures (questionnaires, actigraphy), longitudinal AD plasma biomarkers, amyloid-beta and tau positron emission tomography (PET), magnetoencephalography, as well as neuroimaging analytic measures from all MRI modalities. We describe the PREVENT-AD study, the data shared with the global research community, as well as the model we created to sustain longitudinal follow-ups while also allowing new innovative data collection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is a single-site longitudinal study that started in 2011 with annual follow-up data collection on individuals at risk of Alzheimer's disease who were all cognitively normal at enrolment.</li>\u0000 \u0000 <li>All 387 participants were enrolled between 2011 and 2017 and 306 (79%) of these participants were still in the study as of December 2023.</li>\u0000 \u0000 <li>While the PREVENT-AD dataset was not originally planned to be shared with the global research community, 348 participants retrospectively consented for their data to be shared with researchers worldwide.</li>\u0000 \u0000 <li>The first release of data was in 2019. We now share a second release that includes 6 years of additional follow-up visits, information on clinical progression and novel cognitive, behavioral, genetic, plasma and neuroimaging (amyloid and tau positron emission tomography [PET], magnetoencephalography [MEG], and new magnetic resonance imaging [MRI] sequences) data. It also includes analytic outputs for neuroimaging modalities.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184425","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}
Duygu Sezgin, Flora-Marie Hegerath-Segler, Hannah Christie, Jackie Poos, Kevin Cullen, Emer Meagher, Manuel Gonçalves-Pereira, Horst Christian Vollmar, Cíara O'Reilly, Aisling Mitchell, Salman Alabdulkder, David Neal, Sarah Janus
{"title":"Recommendations for the development and use of technology to support people living with dementia and caregivers: A Delphi study","authors":"Duygu Sezgin, Flora-Marie Hegerath-Segler, Hannah Christie, Jackie Poos, Kevin Cullen, Emer Meagher, Manuel Gonçalves-Pereira, Horst Christian Vollmar, Cíara O'Reilly, Aisling Mitchell, Salman Alabdulkder, David Neal, Sarah Janus","doi":"10.1002/alz.70755","DOIUrl":"10.1002/alz.70755","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This Delphi study, conducted by the INTERDEM Assistive Technology (AT) taskforce, explores existing and future challenges in the development, usability, cost-effectiveness, implementation, and ethics of AT for people living with dementia and caregivers. The study aims to identify key priorities and actions to address these challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A two-round modified electronic Delphi study was conducted with experts from health and social care, dementia research, technology development, people living with dementia, and caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Consensus was reached on 23 key statements highlighting the need for a user-centered approach to AT development. Priorities included integrating AT into care plans, enhancing accessibility, and ensuring collaboration between stakeholders. Ethical considerations, digital literacy, and equitable access were also emphasized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings refine and update previous recommendations on AT development and use. This Delphi study contributes to guiding future research, policy, and practice to ensure AT effectively supports people living with dementia and caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Co-designing technologies with users is crucial to ensure relevance and usability.</li>\u0000 \u0000 <li>Priorities in developing technology include improving access and affordability.</li>\u0000 \u0000 <li>Technology development should aim reducing disparities in digital access.</li>\u0000 \u0000 <li>Future research on technology should be inclusive and reflect real-life needs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182642","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}
Lily Xiao, Shahid Ullah, Ying Yu, Claudia Meyer, Michael Chapman, Langduo Chen, Kai Ping TAN, Sue McKechnie, Mel Ottaway, Andre Queiroz De Andrade, Julie Ratcliffe, Craig Whitehead, Kam Tran, Yao Wang, Alison Kitson
{"title":"Effects of a virtual iSupport Program on carers and people with dementia","authors":"Lily Xiao, Shahid Ullah, Ying Yu, Claudia Meyer, Michael Chapman, Langduo Chen, Kai Ping TAN, Sue McKechnie, Mel Ottaway, Andre Queiroz De Andrade, Julie Ratcliffe, Craig Whitehead, Kam Tran, Yao Wang, Alison Kitson","doi":"10.1002/alz.70747","DOIUrl":"10.1002/alz.70747","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We conducted a virtual iSupport Program intervention for carers of people living with dementia (PLWD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We applied a pragmatic randomized controlled trial to evaluate a multicomponent program delivered virtually in four organizations (July 2022 to December 2024). The primary outcome was quality of life (QoL) of carers and PLWD at 12 months post-baseline, and the secondary outcomes were carers’ self-efficacy, social support, reactions to behavior, PLWD's behavior frequency, hospital admissions, and emergency department presentations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>One hundred forty-nine carers enrolled in the study. The intervention group reported increased mental-health-related QoL points of 12.0 (<i>p</i> < 0.001), self-efficacy points of 14.8 to 18.5 (<i>p</i> < 0.001), social support points of 0.25 (<i>p</i> < 0.028), reduced reactions to behavior points of -0.25 (<i>p</i> < 0.028), and a 60% lower hospital admission rate (<i>p</i> = 0.045) at 12 months compared with the usual care group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The virtual iSupport Program showed benefits for both carers and PLWD in a 12-month intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> TRIAL REGISTRATION</h3>\u0000 \u0000 <p>Australia New Zealand Clinical Trials Registry: ACTRN12622000199718.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A total of 149 dementia carers participated in the virtual iSupport program intervention trial.</li>\u0000 \u0000 <li>The program included skills training, peer support, and access to care services.</li>\u0000 \u0000 <li>The program improved mental health-related quality of life for carers.</li>\u0000 \u0000 <li>The program improved self-efficacy, social support, and reduced distress for carers.</li>\u0000 \u0000 <li>The program reduced 60% hospital admission rate for people with dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188467","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}
Michael C. B. David, Magdalena A. Kolanko, Thomas D. Parker, Ramin Nilforooshan, Karl A. Zimmerman, Cristina Bonet Olivares, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Peter J. Lally, Gregory Scott, CR&T Group of UKDRI, David J. Sharp, Paresh A. Malhotra
{"title":"Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression","authors":"Michael C. B. David, Magdalena A. Kolanko, Thomas D. Parker, Ramin Nilforooshan, Karl A. Zimmerman, Cristina Bonet Olivares, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Peter J. Lally, Gregory Scott, CR&T Group of UKDRI, David J. Sharp, Paresh A. Malhotra","doi":"10.1002/alz.70749","DOIUrl":"10.1002/alz.70749","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>The noradrenergic locus coeruleus (LC) accumulates pathology early in Alzheimer's disease (AD), with LC dysfunction contributing to symptoms and disease progression. We investigated LC and substantia nigra (SN) integrity in healthy controls and AD participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Ninety-three AD participants and 29 controls underwent neuromelanin magnetic resonance imaging. LC and SN contrast, reflecting nucleus integrity, related to cognitive and neuropsychiatric symptoms, as well as cognitive decline and atrophy rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>LC – but not SN – integrity was reduced in AD versus controls (<i>b </i>= −0.39, <i>p</i> = 0.001) and within AD was associated with global cognition (<i>b </i>= 8.53, <i>p</i> = 0.04) and neuropsychiatric symptoms, accounting for SN. An AD subgroup with reduced SN integrity had worse cognition. LC integrity predicted plasma phosphorylated tau protein 217 (<i>b </i>= −0.30, <i>p</i> = 0.03). Lower LC and SN integrities were both related to faster cognitive decline (LC: <i>b </i>= −4.74, <i>p</i> = 0.048; SN: <i>b </i>= −2.27, <i>p</i> = 0.03), accounting for one another.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Catecholaminergic nucleus integrity plays an important role in AD. Both systems are relevant to cognitive performance and decline. LC, in particular, relates closely to symptoms, pathology, and rate of progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In symptomatic AD, LC integrity reflects cortical AD pathology, measured by pTau217.</li>\u0000 \u0000 <li>LC integrity predicts cognitive function in AD, independent of cortical atrophy.</li>\u0000 \u0000 <li>LC and SN integrity independently relate to attentional performance.</li>\u0000 \u0000 <li>Symptoms of anxiety, depression, and apathy are associated with lower LC integrity.</li>\u0000 \u0000 <li>LC and SN relate to cognitive decline rate and left LC predicts atrophy rate.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189485","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}