Alzheimer's & Dementia最新文献

{"title":"Increased sedentary behavior is associated with neurodegeneration and worse cognition in older adults over a 7-year period despite high levels of physical activity","authors":"Marissa A. Gogniat,&nbsp;Omair A. Khan,&nbsp;Judy Li,&nbsp;Chorong Park,&nbsp;W. Hudson Robb,&nbsp;Panpan Zhang,&nbsp;Yunyi Sun,&nbsp;Elizabeth E. Moore,&nbsp;Michelle L. Houston,&nbsp;Kimberly R. Pechman,&nbsp;Niranjana Shashikumar,&nbsp;L. Taylor Davis,&nbsp;Dandan Liu,&nbsp;Bennett A. Landman,&nbsp;Keith R. Cole,&nbsp;Corey J. Bolton,&nbsp;Katherine A. Gifford,&nbsp;Timothy J. Hohman,&nbsp;Kelsie Full,&nbsp;Angela L. Jefferson","doi":"10.1002/alz.70157","DOIUrl":"https://doi.org/10.1002/alz.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sedentary behavior may be a modifiable risk factor for Alzheimer's disease (AD). We examined how sedentary behavior relates to longitudinal brain structure and cognitive changes in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Vanderbilt Memory and Aging Project participants (<i>n</i> = 404) completed actigraphy (7 days), neuropsychological assessment, and 3T brain MRI over a 7-year period. Cross-sectional and longitudinal linear regressions examined sedentary time in relation to brain structure and cognition. Models were repeated testing for effect modification by apolipoprotein E (<i>APOE)</i> ε4 status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In cross-sectional models, greater sedentary time related to a smaller AD-neuroimaging signature (β = -0.0001, <i>p</i> = 0.01) and worse episodic memory (β = -0.001, <i>p</i> = 0.003). Associations differed by <i>APOE</i>-ε4 status. In longitudinal models, greater sedentary time related to faster hippocampal volume reductions (β = -0.1, <i>p</i> = 0.008) and declines in naming (β = -0.001, <i>p</i> = 0.03) and processing speed (β = -0.003, <i>p</i> = 0.02; β = 0.01, <i>p</i> = 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Results support the importance of reducing sedentary time, particularly among aging adults at genetic risk for AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Greater sedentary behavior is related to neurodegeneration and worse cognition.</li>\u0000 \u0000 <li>Associations differed by <i>APOE</i>-ε4 carrier status in cross-sectional models.</li>\u0000 \u0000 <li>Sedentary behavior is an independent risk factor for Alzheimer's disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939350","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":"Comment on “Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US”","authors":"Amin Salehi-Abargouei,&nbsp;Taulant Muka,&nbsp;Tinh-Hai Collet,&nbsp;Kasper P. Kepp,&nbsp;Angeline Chatelan","doi":"10.1002/alz.70035","DOIUrl":"https://doi.org/10.1002/alz.70035","url":null,"abstract":"&lt;p&gt;We are writing this letter in response to the article by Wang et al. recently published in Alzheimer's &amp; Dementia.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; We commend the authors for addressing an important research question using real-world data; however, substantial methodological limitations affecting the observed benefits of semaglutide (Ozempic®) over other glucose-lowering medications need to be mentioned.&lt;/p&gt;&lt;p&gt;First, medications for type 2 diabetes mellitus (T2DM) should always be personalized based on medical history and personal preferences targeting glycemic control, as well as cardioprotection, nephroprotection, and other comorbidities.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For instance, semaglutide usually is (i) not considered a first-line therapy of T2DM and (ii) not prescribed to patients with underweight and/or experiencing weight loss (because it reduces body weight) or those with gastrointestinal conditions. Furthermore, the relationship between body mass and dementia risk is complicated as it probably depends on the nature and severity of the divergent body mass. Underweight in mid- and late-life (and therefore weight loss in middle or older age) might be associated with a higher risk of dementia, whereas late-life overweight could reduce this risk in some contexts.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Additionally, insulin is usually prescribed when (i) the other glucose-lowering medications are ineffective, and/or (ii) hyperglycemia is severe, especially if catabolic states like weight loss, hypertriglyceridemia, and ketosis are present.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Therefore, those with uncontrolled diabetes&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; and with diabetes comorbidities like hypertriglyceridemia,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; which are risk factors for dementia, are candidates for insulin therapy and not for semaglutide. In addition, Figure S4 by Wang et al. shows that patients in the semaglutide group had slightly different healthcare encounters compared to the other groups.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In other words, the insulin group is the worst-off among studied cohorts in a way not fully corrected for. The indication bias related to treatment selection should have been stated in the study limitations and additional analyses controlling for underweight or weight loss should have been added, if possible.&lt;/p&gt;&lt;p&gt;Second, although the authors tried controlling for possible confounders using propensity-score matching, this method is prone to bias if confounders are not all taken into account.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; This seems likely because electronic health records (EHRs) rarely provide valid measures of diet and physical activity, which may be important confounders.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Table 1 suggests this as less than 7% of patients treated with semaglutide or insulin were identified as having “problems with lifestyle,”&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; while lifestyle measures should be actively reinforced before semaglutide prescription. This percentage is likely underest","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939457","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":"Public attitudes toward dementia risk prediction: A mixed-methods study","authors":"Jacqueline J. Claus,&nbsp;Mathijs T. Rosbergen,&nbsp;Marije J. Splinter,&nbsp;Jolande van Heemst,&nbsp;M. Arfan Ikram,&nbsp;Meike W. Vernooij,&nbsp;Frank J. Wolters","doi":"10.1002/alz.14615","DOIUrl":"https://doi.org/10.1002/alz.14615","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Numerous dementia risk prediction models have been developed, but uptake in clinical practice is poor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We determined public attitude toward dementia risk prediction through the means of a focus group (<i>n</i> = 9) and subsequent online survey (<i>n</i> = 687). Thematic content analysis was used for focus group data and descriptive statistics for survey responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Focus group participants expressed reluctance in knowing dementia risk due to fear, emotional burden, and belief that prevention was impossible. Conversely, practical benefits and maximizing present quality of life motivated others to know dementia risk. Of survey respondents, 66.1% would want to know their 10-year risk at present, increasing to 82.3% if preventive medication were available. People perceived their 10-year risk as rather high, yet lower still than their own personal threshold for considering preventive action.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Development and implementation of dementia risk prediction tools require attention for personal actionability and emotional impact of risk communication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Among citizens with a particular interest in dementia, a large group is keen to learn their personal dementia risk, particularly when effective preventive measures are available.</li>\u0000 \u0000 <li>In focus group participants, hesitancy to learn about dementia risk was common, driven by fear, emotional burden, and doubts about the effectiveness of preventive interventions.</li>\u0000 \u0000 <li>The majority of survey participants (72%) believed a healthy lifestyle could reduce dementia risk.</li>\u0000 \u0000 <li>People perceived their 10-year risk as rather high, yet lower still than their own personal threshold for considering preventive action.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939458","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":"Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults","authors":"Axel A. S. Laurell,&nbsp;Elijah Mak,&nbsp;Maria-Eleni Dounavi,&nbsp;Benjamin R. Underwood,&nbsp;Yves Dauvilliers,&nbsp;Robert B. Dudas,&nbsp;Oriane Marguet,&nbsp;Craig W. Ritchie,&nbsp;Ivan Koychev,&nbsp;Brian A. Lawlor,&nbsp;Lorina Naci,&nbsp;Paresh Malhotra,&nbsp;Oriol Grau-Rivera,&nbsp;Juan Domingo Gispert,&nbsp;John T. O'Brien,&nbsp;for the ALFA study,&nbsp;the PREVENT Dementia Investigators","doi":"10.1002/alz.70244","DOIUrl":"https://doi.org/10.1002/alz.70244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (<i>n</i> = 1939), stratified by apolipoprotein E (<i>APOE</i>) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p><i>APOE</i> ε4 homozygotes had a larger anterior–superior hypothalamus compared to heterozygotes and non-carriers, an effect which was driven by younger people in the cohort. <i>APOE</i> ε4 carriers had a higher PSQI global score after age 55, and smaller anterior–superior and tubular–superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior–inferior hypothalamus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This suggests that aging and <i>APOE</i> ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Apolipoprotein E (<i>APOE)</i> ε4 homozygotes ha a larger anterior–superior hypothalamus.</li>\u0000 \u0000 <li><i>APOE</i> ε4 carriers have worse sleep, but only after age 55.</li>\u0000 \u0000 <li>Worse sleep in <i>APOE</i> ε4 carriers was associated with smaller hypothalamic subunits.</li>\u0000 \u0000 <li>Higher age was associated with worse sleep in people with a small hypothalamus.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939496","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":"Relationship between use of anti-platelet agents, oral anti-coagulants, and Aβ burden with cerebral microhemorrhages in cognitively asymptomatic adults","authors":"Marcus D. Gay,&nbsp;Dobri Baldaranov,&nbsp;Michael C. Donohue,&nbsp;Clifford R. Jack Jr.,&nbsp;Reisa A. Sperling,&nbsp;Paul S. Aisen,&nbsp;Michael S. Rafii","doi":"10.1002/alz.70167","DOIUrl":"https://doi.org/10.1002/alz.70167","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cerebral microhemorrhages (CMHs) are detectable by magnetic resonance imaging (MRI). CMHs in deep brain regions are linked to hypertensive vasculopathy, while those in lobar regions with amyloid beta (Aβ) deposition in blood vessels. This study aims to determine the association between anti-thrombotic treatment and CMH prevalence among cognitively asymptomatic adults, and to assess the role of Aβ markers, apolipoprotein E (<i>APOE</i>) ε4 carrier status, and cardiovascular risk factors in CMH development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using baseline data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, we examined CMH presence via 3T MRI, along with medication use, <i>APOE</i> ε4 carrier status, medical history, and blood pressure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Our analysis showed a significantly higher prevalence of CMHs in the A4 cohort (17.3%) compared to the LEARN cohort (2.6%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Factors such as male sex, age, Aβ markers, and <i>APOE</i> ε4 status were significantly associated with higher CMH prevalence in the A4 cohort. However, anti-thrombotic treatment did not show association with overall CMHs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Male sex, age &gt; 75, amyloid beta (Aβ) burden, and apolipoprotein E (<i>APOE</i>) ε4 homozygosity are significantly associated with higher prevalence of CMHs (cerebral microhemorrhages) in a cohort of cognitively asymptomatic individuals.</li>\u0000 \u0000 <li>Male sex, age &gt; 75, Aβ burden, and <i>APOE</i> ε4 homozygosity are significantly associated with higher prevalence of lobar CMHs in a cohort of cognitively asymptomatic individuals.</li>\u0000 \u0000 <li>Anti-platelet or anti-coagulant usage were not associated with an increased prevalence of CMHs in either brain location or overall, in a cohort of cognitively asymptomatic individuals.</li>\u0000 \u0000 <li>History of a lipid disorder is associated with a higher prevalence of lobar CMHs in a cohort of cognitively asymptomatic individuals.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939454","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":"Association of health-care and long-term care resources for patients with dementia with institutionalization and death: Evidence from South Korea","authors":"Sujin Kim,&nbsp;Jaeeon Yoo","doi":"10.1002/alz.70271","DOIUrl":"https://doi.org/10.1002/alz.70271","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The role of community characteristics on supporting the community residence of older adults with dementia has received little attention. This study explores the association of community resources with extending older adults’ stay in community settings and mitigating premature institutionalization and mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from 286,940 patients with dementia in South Korea, this study used Cox proportional hazard models to analyze the relationships among community management, institutionalization, mortality rates, and the availability of long-term care and medical resources at the municipal level, adjusting for individual factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Increased availability of home care nurses and physicians was significantly associated with enhanced community management, showing a noticeable decrease in mortality and institutionalization risk. Additionally, more home care social workers were associated with a reduced institutionalization risk, while an excess of medical and long-term care facilities was linked to a heightened institutionalization risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings underscore the importance of health-care resources aligning with the specific needs of patients with dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Local health-care resources may affect dementia patients’ community residence.</li>\u0000 \u0000 <li>Results reveal physicians and home case nurses lower institutionalization and death.</li>\u0000 \u0000 <li>Study findings indicate home care social workers also reduce institutionalization.</li>\u0000 \u0000 <li>But, more hospital beds and long-term care facilities increase institutionalization.</li>\u0000 \u0000 <li>This underscores the need for nuanced approaches to community-based care.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939357","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":"Association between the use of levodopa/carbidopa, Alzheimer's disease biomarkers, and cognitive decline among participants in the National Alzheimer's Coordinating Center Uniform Data Set","authors":"Zsuzsa Sárkány,&nbsp;Joana Damásio,&nbsp;Sandra Macedo-Ribeiro,&nbsp;Pedro M. Martins","doi":"10.1002/alz.70213","DOIUrl":"https://doi.org/10.1002/alz.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This retrospective study investigates whether exposure to levodopa/carbidopa (LA/CA) medication is associated with modified Alzheimer's disease (AD) trajectories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Multivariate analysis used cerebrospinal fluid (CSF) biomarker information included in the National Alzheimer's Coordinating Center Uniform Data Set for subjects with normal cognition (NC), mild cognitive impairment (MCI), and dementia (DE). Survival analyses examined the progression to MCI/DE and death events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>LA/CA use is associated with lower levels of CSF amyloid beta, phosphorylated-tau (p-tau) and total-tau. After adjusting for age, sex, and apolipoprotein E (APOE) ε4 allele presence, that effect was quantified by negative coefficients of the fitted linear mixed models: <i>p</i>-values &lt; 0.01 in all cases except for p-tau in the MCI subgroup (<i>p</i> = 0.02). No similar effects were identified for other antiparkinsonians. Exposure to LA/CA decreased the progression from MCI to DE (<i>p</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The identified association between LA/CA exposure, AD biomarkers, and progression deserves further investigation in controlled clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>LA/CA is associated with lower levels of CSF biomarkers for AD.</li>\u0000 \u0000 <li>This effect is not observed when other antiparkinsonian drugs are used.</li>\u0000 \u0000 <li>LA/CA is also associated with delayed progression to dementia by AD patients with MCI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939451","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":"Choroidal and retinal vascular changes in adults with Down syndrome: Insights into the Alzheimer's disease continuum","authors":"Jamie Mitchell,&nbsp;Adam Threlfall,&nbsp;Kenneth Sloan,&nbsp;Luke Smyth,&nbsp;Jessica Beresford-Webb,&nbsp;Madeleine J. Walpert,&nbsp;Tunde Peto,&nbsp;Tom MacGillivray,&nbsp;Antony Holland,&nbsp;Imre Lengyel,&nbsp;Lajos Csincsik","doi":"10.1002/alz.70228","DOIUrl":"https://doi.org/10.1002/alz.70228","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Retinal and choroidal vascular changes have been proposed as a non-invasive central nervous system (CNS) proxy for clinical trials in Alzheimer's disease (AD). However, their role in Down syndrome (DS), the largest genetically predisposed group for AD, remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted ultra-widefield and optical coherence tomography imaging on 24 individuals with DS and 17 controls and extracted various vascular parameters. Data were analyzed using logistic and linear regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The DS retinae exhibited supernumerary vessels that were wider and thinned more rapidly along their paths (<i>p</i> = 0.01). There was a more complex central retinal (<i>p</i> = 0.047) and a less complex peripheral retinal vascular tree (<i>p</i> = 0.001), with increased numbers of peripheral microvascular abnormalities (<i>p</i> = 0.038) and reduced choroid vascularity index in DS (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We found that retinal and choroidal vascular changes are present in DS adults before the clinical onset of AD and might become early surrogates for cerebral vascular abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Eye imaging in DS showed retinal and choroidal changes seen in AD.</li>\u0000 \u0000 <li>Far peripheral retinal microaneurysms and hemorrhages associated to DS.</li>\u0000 \u0000 <li>Wider and faster thinning vessels associated to DS.</li>\u0000 \u0000 <li>Reduced vascular tree complexity in the peripheral retina linked to DS.</li>\u0000 \u0000 <li>Lower choroidal vascularity associated with DS.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939455","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":"Misfolded α-synuclein co-occurrence with Alzheimer's disease proteinopathy","authors":"Erin M. Jonaitis,&nbsp;Karen MacLeod,&nbsp;Jennifer Lamoureux,&nbsp;Beckie Jeffers,&nbsp;Rachel L. Studer,&nbsp;John Middleton,&nbsp;Rachael E. Wilson,&nbsp;Nathaniel A. Chin,&nbsp;Ozioma C. Okonkwo,&nbsp;Barbara B. Bendlin,&nbsp;Sanjay Asthana,&nbsp;Cynthia M. Carlsson,&nbsp;Catherine L. Gallagher,&nbsp;Bruce Hermann,&nbsp;Sean McEvoy,&nbsp;Gwendlyn Kollmorgen,&nbsp;Henrik Zetterberg,&nbsp;Luis Concha-Marambio,&nbsp;Sterling C. Johnson,&nbsp;Russ M. Lebovitz,&nbsp;Rebecca E. Langhough","doi":"10.1002/alz.70205","DOIUrl":"https://doi.org/10.1002/alz.70205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Multi-etiology dementia necessitates in vivo markers of copathologies including misfolded <span></span><math>\u0000 <semantics>\u0000 <mi>α</mi>\u0000 <annotation>${{alpha}}$</annotation>\u0000 </semantics></math>-synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplification assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Cerebrospinal fluid (CSF) was obtained from 420 participants in two AD risk cohorts (35% male; 91% cognitively unimpaired; mean [standard deviation] age, 65.42 [7.78] years; education, 16.17 [2.23]) years). synSAA results were compared to phosphorylated tau (T), amyloid beta (A), and clinical outcomes. Longitudinal cognition was modeled with mixed effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Syn positivity (synSAA+) co-occurred with T (in synSAA+ vs. synSAA−, 36% vs. 20% T+; P<i>p</i> = 0.011) and with cognitive impairment (10% vs. 7% mild cognitive impairment; 10% vs. 0% dementia; <i>p</i> = 0.00050). synSAA+ participants’ cognitive performance declined ≈ 40% faster than synSAA– for Digit Symbol Substitution, but not other tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Findings support prevalent syn copathology in a mostly unimpaired AD risk cohort. Relationships with progression should be evaluated once more have declined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In a middle-aged sample, misfolded <span></span><math>\u0000 <semantics>\u0000 <mi>α</mi>\u0000 <annotation>${{alpha}}$</annotation>\u0000 </semantics></math>-synuclein (syn) co-occurred with phosphorylated tau181 (T).</li>\u0000 \u0000 <li>syn+/T+ status was linked with higher levels of other cerebrospinal fluid biomarkers.</li>\u0000 \u0000 <li>syn+ individuals were more likely than syn– to be cognitively impaired.</li>\u0000 \u0000 <li>syn+ status was linked to faster decline on an executive function task.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939222","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":"Early detection of Alzheimer's disease using deep learning methods","authors":"Anthony Chidubem Mmadumbu,&nbsp;Faisal Saeed,&nbsp;Fuad Ghaleb,&nbsp;Sultan Noman Qasem","doi":"10.1002/alz.70175","DOIUrl":"https://doi.org/10.1002/alz.70175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD), a leading cause of dementia, requires early detection for effective intervention. This study employs AI to analyze multimodal datasets, including clinical, biomarker, and neuroimaging data, using hybrid deep learning frameworks to improve predictive accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A novel framework was developed, including trained models for structured data and magnetic resonance images. The structured data model used a long short-term memory (LSTM) for temporal dependencies and a feedforward neural network (FNN) for static patterns. The MRI-based model employed ResNet50 and MobileNetV2 to extract spatial features. Models were applied on National Alzheimer's Coordinating Centre (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) datasets and compared to previous works.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The MRI-based model achieved 96.19% accuracy on the ADNI dataset, while the hybrid model attained 99.82% accuracy on NACC dataset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study highlights hybrid AI models' potential in AD detection, enabling earlier interventions and improved detection outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>AI models were explored for early AD detection using NACC and ADNI datasets.</li>\u0000 \u0000 <li>Achieved high accuracy with LSTM on NACC data, showing potential for early AD diagnosis.</li>\u0000 \u0000 <li>Evaluated transfer learning models (MobileNetV2, ResNet-50) to address data limitations.</li>\u0000 \u0000 <li>A method is proposed for the careful validation of transfer learning models in medical brain diagnostics.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 5","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939220","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}