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Perspective: Emerging challenges for a future ADNI
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.14534
Zaven Khachaturian, Maria C. Carrillo, Ara S. Khachaturian

In the last two decades, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has significantly advanced our understanding, technologies, and methods for detecting and diagnosing Alzheimer's disease and related dementias. This perspective proposes repurposing ADNI to address emerging research and healthcare challenges. The focus would shift toward early detection of cognitive impairment, discovering new interventions, evaluating non-pharmacological treatments, adopting a public health approach, and enrolling a diverse international cohort. Key elements of this new model include emphasizing vascular-metabolic factors, leveraging biomarkers, and enhancing computational capabilities. By reimagining ADNI's mission and framework, the initiative may be better poised to tackle the evolving complexities of dementia research and improve patient outcomes through a more comprehensive, multidisciplinary approach.

Highlights

  • ADNI should be repurposed for early detection and intervention in cognitive decline.
  • This would emphasize vascular-metabolic factors and biomarkers in dementia research.
  • It advocates for non-pharmacological evaluations and a public health approach.
  • It promotes international cohort studies and enhanced computational capacity.
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引用次数: 0
Complexity of developing a nationwide model for a dementia registry in Egypt: A qualitative study 在埃及开发全国性痴呆症登记模式的复杂性:定性研究
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.70011
Shimaa A. Heikal, Ghada Barsoum, Mohamed Salama

INTRODUCTION

The increased interest in evidence-based medicine has led to the emergence of disease registries worldwide to help tackle the impact of chronic diseases. A national dementia registry in Egypt would provide a valuable source of patient data that will significantly advance the disease management strategies, quality of patient care, and impact health policy- and decision making.

METHODS

This study investigates the complexity of creating a disease registry for dementia in Egypt by interviewing 24 experts to provide recommendations for the most appropriate registry model to be developed.

RESULTS

Several core themes emerged from the analysis discussing many points that should direct the creation of any registry in Egypt in terms of functionality, planning, comprehension, governance, ethics, and challenges to avoid.

DISCUSSION

Developing such a dataset is beneficial to the Egyptian health-care system, which makes the investment worthwhile. Support and collaborative work from all stakeholders, along with suitable funding, are essential elements of the proper implementation of the project.

Highlights

  • Building a dementia registry is essential to progress research in understudied populations
  • Qualitative analysis of 24 experts interviews provided insightful plan for dementia registry
  • Core domains to address include: functionality, planning, comprehension, governance, ethics, and challenges to avoid.
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引用次数: 0
Early presentations of dementia in a diverse population
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.14578
Sedigheh Zabihi, Jonathan P Bestwick, Mark Jitlal, Phazha LK Bothongo, Qiqi Zhang, Christine Carter, Moïse Roche, Sarah Morgan-Trimmer, Yvonne Birks, Mark Wilberforce, Ruth Dobson, Alastair J Noyce, John Robson, Fiona M Walter, Claudia Cooper, Charles R Marshall

INTRODUCTION

Improved recognition of non-cognitive presentations of dementia could reduce inequalities in dementia diagnosis, particularly if sociocultural factors influence help-seeking for cognitive symptoms.

METHODS

We conducted a nested case-control study using electronic healthcare records from primary care practices in East London, United Kingdom, to assess associations between prediagnostic presentations to primary care and subsequent dementia diagnosis.

RESULTS

We included 4137 individuals with a dementia diagnosis and 15,754 controls in the matched analysis. In addition to memory difficulties, a range of symptoms were more common in the decade before diagnosis, including depression, anxiety, use of antipsychotics, insomnia, constipation, incontinence, hypotension, hearing loss, imbalance, and dizziness.

DISCUSSION

A range of non-cognitive presentations are seen during the prodromal period of dementia in a diverse population. Improved recognition of these associations and their variation by ethnicity could increase access to dementia diagnosis through improved recognition of early features in people from different sociocultural backgrounds.

Highlights

  • Prediagnostic signs of dementia include cognitive and non-cognitive symptoms.
  • Psychiatric symptoms are common up to a decade prior to a dementia diagnosis.
  • Autonomic prediagnostic symptoms are more common among South Asian groups.
  • The importance of prediagnostic symptoms of dementia varies by ethnicity.
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引用次数: 0
Eating and swallowing care disparities in persons with dementia: A conceptual framework
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.70028
Raele Donetha Loy, Nicole Rogus-Pulia, Fred Ketchum, Michelle Troche, Anaïs Rameau, Harrison N. Jones, Luis Riquelme, Andrea Gilmore-Bykovskyi, Manish N. Shah, Amy Kind

INTRODUCTION

Eating and swallowing difficulties are prevalent and distressing among persons living with dementia (PLWD). These challenges may be especially burdensome for PLWD in lower-resourced settings, where environmental factors such as social support, health-care infrastructure, and food access are critical for meeting quality standards of eating and swallowing care. However, clinical practices and research methods have not sufficiently focused on the lived environment to promote high-quality, socially and culturally aligned management approaches.

METHODS

To address this gap, we developed a conceptual framework informed by the literature, grounded in ecological systems and fundamental cause theories, and refined through iterative discussion.

RESULTS

Our framework highlights individual-, system-, and community-level factors and resources influencing person-centered eating and swallowing care for PLWD. It identifies areas at risk for inequitable care along the swallowing management continuum.

DISCUSSION

We propose future research areas to help health-care providers reconcile the demands of eating and swallowing care with the lived realities of PLWD.

Highlights

  • There are eating/swallowing care disparities among persons living with dementia.
  • We introduce a conceptual framework applying social and structural determinants of health to eating/swallowing care.
  • We also recommend areas to address disparities and improve eating/swallowing care.
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引用次数: 0
Individual and joint associations between sleep duration and physical activity with cognitive function: a longitudinal analysis among middle-aged and older adults in China
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.70049
Zhiyi Zhang
<p>I read the article written by Hongwei Liu and his colleagues with interest, and I would like to commend the author for conducting such a comprehensive longitudinal study, examining the relationship between sleep time, physical activity, and cognitive function among middle-aged and elderly people in China.<span><sup>1</sup></span> The research provides valuable insights into the potential effects of lifestyle factors, specifically sleep and physical activity, on cognitive aging. However, I would like to offer several suggestions and comments for consideration.</p><p>First, although the study considered sleep duration, it did not delve into the impact of sleep quality.<span><sup>2, 3</sup></span> Research has shown that sleep quality has a significant impact on cognitive function, and analyzing solely based on sleep duration may overlook other important factors that affect cognitive function, such as sleep interruption, lack of deep sleep, etc., which may have an impact on cognition and, thus, affect the accuracy of research results.<span><sup>4</sup></span></p><p>Although this study employed lagged time series models to examine causal relationships, the possibility of reverse causation cannot be completely ruled out, particularly since early-stage cognitive decline may influence both sleep patterns and physical activity levels.<span><sup>5</sup></span> Specifically, deteriorating cognitive function could alter individuals' sleep habits and physical activity behaviors, making it challenging to fully disentangle the direction of causality. Future research should implement methodological approaches that minimize the potential impact of reverse causation to ensure greater validity of findings.<span><sup>6-8</sup></span></p><p>While this study thoroughly examined the relationships between sleep and physical activity, it may not have adequately addressed the potential non-linear effects of these variables. For instance, moderate physical activity might enhance cognitive function, whereas excessive physical activity could potentially yield adverse effects.<span><sup>9</sup></span> The analyses conducted in this study may not have fully captured such non-linear relationships. Furthermore, the lack of detailed categorization of physical activity types and intensities represents another limitation, as different forms of exercise (such as aerobic exercise and strength training) may differentially impact cognitive function, potentially affecting the precision of our findings.<span><sup>10</sup></span></p><p>Based on our findings, we propose implementing a three-tiered response system for cognitive health management. The first tier focuses on broad public health education, promoting awareness of cognitive health through campaigns that emphasize the importance of proper sleep habits and appropriate physical activity levels. The second tier targets high-risk populations, such as elderly individuals and those with family history of cognitive decline, providing
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引用次数: 0
Education and midlife cognitive functioning: Evidence from the High School and Beyond cohort 教育与中年认知功能:高中及高中以上组群的证据
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.70015
Chandra Muller, Eric Grodsky, Adam M. Brickman, Jennifer J. Manly, Koit Hung, Michael J. Culbertson, John Robert Warren

INTRODUCTION

Educational attainment is associated with midlife cognitive functioning. However, degree attainment is the culmination of complex and unequal processes involving students’ backgrounds, the opportunities that schools provide them, and their performance within those schools─all of which may also shape midlife cognition. What do educational gradients in midlife cognition look like using a richer conceptualization and measures of “education?”

METHODS

We use data from High School and Beyond (HS&B:80)─a large, nationally representative sample of Americans followed from high school through age ∼60─to assess the role of education in stratifying midlife cognition.

RESULTS

High schools’ academic and socioeconomic environments predict midlife cognition primarily through their associations with their students’ academic performance. Student academic performance strongly predicts midlife cognition, partially through its association with degree attainment.

DISCUSSION

Inequalities in educational opportunities and in students’ performance in schools shape midlife cognition─even among students with the same attained degrees.

Highlights

  • Degree attainment predicts midlife cognitive functioning, but a large portion of that association is accounted for by students’ high school academic performance as measured by test scores, grades, and course completion.
  • High school contexts and learning opportunities predict midlife cognition mainly because they play a role in shaping students’ academic performance.
  • Understanding the potential benefits of education for later-life cognitive functioning requires attention to broader schooling processes and to students’ academic performance beyond degree attainment.
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引用次数: 0
Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window 血浆 p-tau217 能识别认知功能正常、但在 10 年内会出现认知障碍的老年人
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-26 DOI: 10.1002/alz.14537
Yara Yakoub, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Christine Déry, Cherie Strikwerda-Brown, Frédéric St-Onge, Valentin Ourry, Michael Schöll, Maiya R. Geddes, Simon Ducharme, Maxime Montembeault, Pedro Rosa-Neto, Jean-Paul Soucy, John C. S. Breitner, Henrik Zetterberg, Kaj Blennow, Judes Poirier, Sylvia Villeneuve, PREVENT−AD Research Group

INTRODUCTION

We assessed the prognostic accuracy of plasma p-tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow-up of 5.65 years after plasma collection (range 1.01–10.47).

METHODS

We included 215 participants from the PREVENT−AD cohort with plasma Aβ42/40 and p-tau217, 159 with cerebrospinal fluid (CSF) Aβ42/40 and p-tau217, and 155 with 18F-NAV4694 and 18F-flortaucipir PET scans. MCI progression was determined by multidisciplinary consensus among memory experts blind to biomarker and genetic information.

RESULTS

Cox proportional hazard models indicated a greater progression rate in A+T+plasma and A−T+plasma compared to A−T−plasma individuals (HR = 7.81 [95% CI = 3.92 to 15.59] and HR = 4.25 [1.60–11.31] respectively). Similar results were found with CSF (HR = 3.63 [1.72–7.70]) and PET (HR = 9.30 [3.67–23.55]).

DISCUSSION

Plasma p-tau217 is a prognostic marker for identifying individuals who will develop cognitive impairment within ten years.

Highlights

  • Elevated plasma p-tau217 levels in CU individuals indicate future clinical progression.
  • Adding plasma Aβ42/40 status to p-tau markers did not improve the prediction to MCI.
  • All individuals with abnormal tau PET measured in a temporal meta-ROI progressed to MCI.
{"title":"Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window","authors":"Yara Yakoub,&nbsp;Fernando Gonzalez-Ortiz,&nbsp;Nicholas J. Ashton,&nbsp;Christine Déry,&nbsp;Cherie Strikwerda-Brown,&nbsp;Frédéric St-Onge,&nbsp;Valentin Ourry,&nbsp;Michael Schöll,&nbsp;Maiya R. Geddes,&nbsp;Simon Ducharme,&nbsp;Maxime Montembeault,&nbsp;Pedro Rosa-Neto,&nbsp;Jean-Paul Soucy,&nbsp;John C. S. Breitner,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Judes Poirier,&nbsp;Sylvia Villeneuve,&nbsp;PREVENT−AD Research Group","doi":"10.1002/alz.14537","DOIUrl":"https://doi.org/10.1002/alz.14537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We assessed the prognostic accuracy of plasma p-tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow-up of 5.65 years after plasma collection (range 1.01–10.47).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 215 participants from the PREVENT−AD cohort with plasma Aβ<sub>42/40</sub> and p-tau217, 159 with cerebrospinal fluid (CSF) Aβ<sub>42/40</sub> and p-tau217, and 155 with <sup>18</sup>F-NAV4694 and <sup>18</sup>F-flortaucipir PET scans. MCI progression was determined by multidisciplinary consensus among memory experts blind to biomarker and genetic information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Cox proportional hazard models indicated a greater progression rate in A+T+<sub>plasma</sub> and A−T+<sub>plasma</sub> compared to A−T−<sub>plasma</sub> individuals (HR = 7.81 [95% CI = 3.92 to 15.59] and HR = 4.25 [1.60–11.31] respectively). Similar results were found with CSF (HR = 3.63 [1.72–7.70]) and PET (HR = 9.30 [3.67–23.55]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau217 is a prognostic marker for identifying individuals who will develop cognitive impairment within ten years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Elevated plasma p-tau217 levels in CU individuals indicate future clinical progression.</li>\u0000 \u0000 <li>Adding plasma Aβ<sub>42/40</sub> status to p-tau markers did not improve the prediction to MCI.</li>\u0000 \u0000 <li>All individuals with abnormal tau PET measured in a temporal meta-ROI progressed to MCI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490052","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}
引用次数: 0
Prevalence and factors associated with dementia in Lesotho: A cross-sectional, population-based study
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-25 DOI: 10.1002/alz.14614
Natalie E. Johnson, Jennifer M. Belus, Felix Gerber, Tristan T. Lee, Irene Ayakaka, Pearl Letsoela, Manthabiseng Molulela, Frédérique Chammartin, Alain Amstutz, Niklaus D. Labhardt

INTRODUCTION

Limited research has examined dementia prevalence and associated factors in Lesotho. This study investigates dementia prevalence and the associated factors in Lesotho.

METHODS

A survey in Lesotho included 1738 participants screened for dementia and potential associated factors with a focus on modifiable factors. Associations were evaluated using logistic regression models.

RESULTS

The median age was 66 years, with 54.83% women. The prevalence of dementia was 4.89%. Those with depressive symptoms (adjusted odds ratio [aOR]: 3.97, 95% confidence interval [CI]: 1.39–11.30), age ≥ 75 (aOR: 2.68, 95% CI: 1.42–5.04), and underweight (aOR 2.30, 95% CI: 1.23–4.29) had increased odds of dementia. Those with moderate (aOR: 0.32, 95% CI: 0.17–0.58) to high (aOR: 0.35, 95% CI: 0.16–0.77) physical activity and obesity (aOR: 0.30, 95% CI: 0.11–0.80) presented lower odds for dementia.

DISCUSSION

This study provides a contemporary estimate of dementia prevalence in Lesotho, highlighting an association with modifiable factors.

Highlights

  • In Lesotho there is a probable dementia prevalence of 4.89%, aligning with regional estimates for Africa.
  • Depression, older age, being underweight, and low physical activity were associated with increased odds of dementia.
  • Moderate to high physical activity and obesity were associated with lower dementia odds.
  • Further study of the association of dementia with potentially modifiable factors in low- and middle-income countries is warranted.
{"title":"Prevalence and factors associated with dementia in Lesotho: A cross-sectional, population-based study","authors":"Natalie E. Johnson,&nbsp;Jennifer M. Belus,&nbsp;Felix Gerber,&nbsp;Tristan T. Lee,&nbsp;Irene Ayakaka,&nbsp;Pearl Letsoela,&nbsp;Manthabiseng Molulela,&nbsp;Frédérique Chammartin,&nbsp;Alain Amstutz,&nbsp;Niklaus D. Labhardt","doi":"10.1002/alz.14614","DOIUrl":"https://doi.org/10.1002/alz.14614","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Limited research has examined dementia prevalence and associated factors in Lesotho. This study investigates dementia prevalence and the associated factors in Lesotho.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A survey in Lesotho included 1738 participants screened for dementia and potential associated factors with a focus on modifiable factors. Associations were evaluated using logistic regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The median age was 66 years, with 54.83% women. The prevalence of dementia was 4.89%. Those with depressive symptoms (adjusted odds ratio [aOR]: 3.97, 95% confidence interval [CI]: 1.39–11.30), age ≥ 75 (aOR: 2.68, 95% CI: 1.42–5.04), and underweight (aOR 2.30, 95% CI: 1.23–4.29) had increased odds of dementia. Those with moderate (aOR: 0.32, 95% CI: 0.17–0.58) to high (aOR: 0.35, 95% CI: 0.16–0.77) physical activity and obesity (aOR: 0.30, 95% CI: 0.11–0.80) presented lower odds for dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides a contemporary estimate of dementia prevalence in Lesotho, highlighting an association with modifiable factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In Lesotho there is a probable dementia prevalence of 4.89%, aligning with regional estimates for Africa.</li>\u0000 \u0000 <li>Depression, older age, being underweight, and low physical activity were associated with increased odds of dementia.</li>\u0000 \u0000 <li>Moderate to high physical activity and obesity were associated with lower dementia odds.</li>\u0000 \u0000 <li>Further study of the association of dementia with potentially modifiable factors in low- and middle-income countries is warranted.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489872","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}
引用次数: 0
Mechanisms of comorbidity between Alzheimer's disease and pain
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-25 DOI: 10.1002/alz.14605
Kaifang Yao, Shenjun Wang, Zhifang Xu, Zezhi Fan, Zhihan Chen, Peng Jia, Shiwei Tu, Yangyang Liu, Xiaowei Lin, Yuan Xu, Yuxing Fang, Baomin Dou, Yi Guo

Clinical studies have revealed a significant correlation between pain and neurodegenerative diseases, particularly Alzheimer's disease (AD). However, due to cognitive and speech impairments, AD patients, especially those in moderate to severe stages, are often overlooked in pain management. The challenges in obtaining pain-related information from this population exacerbate the issue. Although recent clinical research has increasingly recognized the comorbidity of AD and pain, the pathological alterations and interactive mechanisms underlying this relationship remain inadequately explored. This review provides a comprehensive analysis of the clinical features and pathological mechanisms of AD with and without pain comorbidity. It examines underlying processes, including neuroinflammation, peripheral-central immune interactions, and neurotransmitter dynamics. Furthermore, it highlights current pain assessment and management strategies in AD patients. By offering a theoretical framework, this review aims to support the development of effective pain management approaches and serve as a reference for clinical interventions targeting AD-associated pain.

Highlights

  • The comorbidity between AD and CP encompasses multiple interrelated biological pathways, such as neurodegeneration and inflammatory responses.
  • The damage to neurons and synapses in AD patients influences the brain regions responsible for processing pain, thereby reducing the pain response.
  • Neuroinflammation plays a vital role in the development of both AD and CP. Enhanced inflammatory responses have an impact on the CNS and promote sensitization.
  • Common neurotransmitter alterations exist in the comorbidity of AD and CP, influencing cognition, emotion, and pain perception.
{"title":"Mechanisms of comorbidity between Alzheimer's disease and pain","authors":"Kaifang Yao,&nbsp;Shenjun Wang,&nbsp;Zhifang Xu,&nbsp;Zezhi Fan,&nbsp;Zhihan Chen,&nbsp;Peng Jia,&nbsp;Shiwei Tu,&nbsp;Yangyang Liu,&nbsp;Xiaowei Lin,&nbsp;Yuan Xu,&nbsp;Yuxing Fang,&nbsp;Baomin Dou,&nbsp;Yi Guo","doi":"10.1002/alz.14605","DOIUrl":"https://doi.org/10.1002/alz.14605","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Clinical studies have revealed a significant correlation between pain and neurodegenerative diseases, particularly Alzheimer's disease (AD). However, due to cognitive and speech impairments, AD patients, especially those in moderate to severe stages, are often overlooked in pain management. The challenges in obtaining pain-related information from this population exacerbate the issue. Although recent clinical research has increasingly recognized the comorbidity of AD and pain, the pathological alterations and interactive mechanisms underlying this relationship remain inadequately explored. This review provides a comprehensive analysis of the clinical features and pathological mechanisms of AD with and without pain comorbidity. It examines underlying processes, including neuroinflammation, peripheral-central immune interactions, and neurotransmitter dynamics. Furthermore, it highlights current pain assessment and management strategies in AD patients. By offering a theoretical framework, this review aims to support the development of effective pain management approaches and serve as a reference for clinical interventions targeting AD-associated pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The comorbidity between AD and CP encompasses multiple interrelated biological pathways, such as neurodegeneration and inflammatory responses.</li>\u0000 \u0000 <li>The damage to neurons and synapses in AD patients influences the brain regions responsible for processing pain, thereby reducing the pain response.</li>\u0000 \u0000 <li>Neuroinflammation plays a vital role in the development of both AD and CP. Enhanced inflammatory responses have an impact on the CNS and promote sensitization.</li>\u0000 \u0000 <li>Common neurotransmitter alterations exist in the comorbidity of AD and CP, influencing cognition, emotion, and pain perception.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481351","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}
引用次数: 0
A systematic exposure-wide framework leveraging machine learning to identify multidomain exposure factors and their joint influence on cognitive function: Evidence from a neurological cohort
IF 13 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-25 DOI: 10.1002/alz.14624
Jingtao Wu, Bowen Yin, Rui Wen, Huanting Pei, Siqi Zhu, Jiaxin Zhao, Yanbing Li, Ming Yang, Yaoyu Hu, Qun Xu, Ang Li, Yuxia Ma

INTRODUCTION

Cognitive decline has become a growing public concern, yet large-scale exposure data identifying the contributing factors remain limited.

METHODS

We conducted an exposure-wide association study involving 1142 participants and 207 exposures, using machine learning to assess the relative contribution and joint effects of key factors. Cluster analysis and intervention simulation trials helped identify high-risk subpopulations and the potential benefits of targeted interventions.

RESULTS

In adjusted mixed models, the socioeconomic status domain emerged as the strongest predictor of longitudinal global cognitive score (β = 2.91, < 0.0001, q < 0.0001), while the dietary domain also played an important role in memory function. The cluster analysis found that the “unfavorable lifestyle” dominated phenotype was associated with the poorest cognitive outcomes. Simulation trials indicated that cognitive scores could improve by shifting individuals from unfavorable to favorable phenotypes.

DISCUSSION

Cognitive health requires multidomain interventions, particularly in the socioeconomic and dietary fields, and necessitates collaboration between government and individuals.

Highlights

  • The exposure-wide association study design, which assesses a broad range of exposures, is used to identify novel variables and understand their contributions to cognitive function.
  • The findings from the multidomain analysis indicate that socioeconomic status is the most significant contributor to global cognitive function, while diet plays the largest role in memory function.
  • Increasing the proportion of favorable phenotypes through multidomain interventions can significantly enhance public cognitive health.
{"title":"A systematic exposure-wide framework leveraging machine learning to identify multidomain exposure factors and their joint influence on cognitive function: Evidence from a neurological cohort","authors":"Jingtao Wu,&nbsp;Bowen Yin,&nbsp;Rui Wen,&nbsp;Huanting Pei,&nbsp;Siqi Zhu,&nbsp;Jiaxin Zhao,&nbsp;Yanbing Li,&nbsp;Ming Yang,&nbsp;Yaoyu Hu,&nbsp;Qun Xu,&nbsp;Ang Li,&nbsp;Yuxia Ma","doi":"10.1002/alz.14624","DOIUrl":"10.1002/alz.14624","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cognitive decline has become a growing public concern, yet large-scale exposure data identifying the contributing factors remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted an exposure-wide association study involving 1142 participants and 207 exposures, using machine learning to assess the relative contribution and joint effects of key factors. Cluster analysis and intervention simulation trials helped identify high-risk subpopulations and the potential benefits of targeted interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In adjusted mixed models, the socioeconomic status domain emerged as the strongest predictor of longitudinal global cognitive score (<i>β</i> = 2.91, <i>p </i>&lt; 0.0001, <i>q</i> &lt; 0.0001), while the dietary domain also played an important role in memory function. The cluster analysis found that the “unfavorable lifestyle” dominated phenotype was associated with the poorest cognitive outcomes. Simulation trials indicated that cognitive scores could improve by shifting individuals from unfavorable to favorable phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Cognitive health requires multidomain interventions, particularly in the socioeconomic and dietary fields, and necessitates collaboration between government and individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The exposure-wide association study design, which assesses a broad range of exposures, is used to identify novel variables and understand their contributions to cognitive function.</li>\u0000 \u0000 <li>The findings from the multidomain analysis indicate that socioeconomic status is the most significant contributor to global cognitive function, while diet plays the largest role in memory function.</li>\u0000 \u0000 <li>Increasing the proportion of favorable phenotypes through multidomain interventions can significantly enhance public cognitive health.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486360","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}
引用次数: 0
期刊
Alzheimer's & Dementia
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