Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00323-0
Lorraine V Kaila, Manabu Ikeda, Janet Sultana, Leonidas Chouliaras, John T O’Brien, John-Paul Taylor
Dementia with Lewy bodies has a complex clinical presentation, with symptoms spanning cognitive, neuropsychiatric, motor, autonomic, and sleep domains. The disorder causes high morbidity, is associated with high caregiver burden, and can result in considerable health-care costs. Although symptomatic treatments remain scarce, emerging evidence supports a multipronged approach that integrates pharmacological and non-pharmacological interventions that target different signs and symptoms. Novel frameworks, such as the DIAMOND Lewy toolkit, provide structured management guidance. Beyond symptom control, research is at a turning point, with increasing focus on disease-modifying therapies. Ongoing clinical trials are exploring many therapeutic targets, including α-synuclein aggregation and neuroinflammation. Other potential targets in the treatment of dementia with Lewy bodies include amyloid β, given that the presence of Alzheimer's disease copathology is common in patients with this disease.
{"title":"The evolving therapeutic landscape of dementia with Lewy bodies","authors":"Lorraine V Kaila, Manabu Ikeda, Janet Sultana, Leonidas Chouliaras, John T O’Brien, John-Paul Taylor","doi":"10.1016/s1474-4422(25)00323-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00323-0","url":null,"abstract":"Dementia with Lewy bodies has a complex clinical presentation, with symptoms spanning cognitive, neuropsychiatric, motor, autonomic, and sleep domains. The disorder causes high morbidity, is associated with high caregiver burden, and can result in considerable health-care costs. Although symptomatic treatments remain scarce, emerging evidence supports a multipronged approach that integrates pharmacological and non-pharmacological interventions that target different signs and symptoms. Novel frameworks, such as the DIAMOND Lewy toolkit, provide structured management guidance. Beyond symptom control, research is at a turning point, with increasing focus on disease-modifying therapies. Ongoing clinical trials are exploring many therapeutic targets, including α-synuclein aggregation and neuroinflammation. Other potential targets in the treatment of dementia with Lewy bodies include amyloid β, given that the presence of Alzheimer's disease copathology is common in patients with this disease.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00399-0
Christopher G Goetz
<h2>Section snippets</h2><section><section><h2>The anatomo-clinical method [la méthode anatomo-clinique]: anchor of neurology</h2>As the first pillar of Charcot's legacy, his <span><span>anatomo-clinical method</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> remains the fundamental underpinning of contemporary neurology. It serves as a reciprocal effort between hospital or clinic and laboratory to match clinical signs and anatomical lesions. Charcot adapted the methodology of René Laennec (1781–1826) to the brain and spinal cord, peripheral nerves, and muscles. The exercise began with the systematic evaluation of the vast clinical service in Charcot's medical unit at the</section></section><section><section><h2>Neurology as a multidisciplinary and enriched by other scientific fields</h2>As the second pillar, on his neurological service, Charcot introduced a wide variety of strategies that took advantage of new discoveries from branches of science other than those traditionally aligned to clinical medicine, like physiology or chemistry. Fascinated by the new technology of photography, Charcot created a highly sophisticated <span><span>medical photographic division</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> that included not only cameras for still photographs, but also multi-image cameras attached to a metronome to capture the</section></section><section><section><h2>Heredity as the primary etiology of neurological diseases</h2>Charcot largely assumed that heredity was the fundamental causative agent underlying primary neurological disorders. Preceding Gregor Mendell and other pioneers in the field of genetics, Charcot held firmly that his patients carried a <span><span>familial trait</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, “<em>la tache familiale neurologique.”</em> Creating genealogical trees, he insisted that he could identify neurological symptom clusters in siblings, parents, and grandparents of his patients that related directly to the cause of his patient's plight. In</section></section><section><section><h2>200 years</h2>The three pillars cited here provide a reference to a scientific legacy, but because Charcot's lectures remain available for study, his <span><span>human legacy</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> can also be appreciated. His elegantly stated advice to hi
{"title":"Si je ne me trompe pas: Charcot's neurological legacy in the 21st century","authors":"Christopher G Goetz","doi":"10.1016/s1474-4422(25)00399-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00399-0","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>The anatomo-clinical method [la méthode anatomo-clinique]: anchor of neurology</h2>As the first pillar of Charcot's legacy, his <span><span>anatomo-clinical method</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> remains the fundamental underpinning of contemporary neurology. It serves as a reciprocal effort between hospital or clinic and laboratory to match clinical signs and anatomical lesions. Charcot adapted the methodology of René Laennec (1781–1826) to the brain and spinal cord, peripheral nerves, and muscles. The exercise began with the systematic evaluation of the vast clinical service in Charcot's medical unit at the</section></section><section><section><h2>Neurology as a multidisciplinary and enriched by other scientific fields</h2>As the second pillar, on his neurological service, Charcot introduced a wide variety of strategies that took advantage of new discoveries from branches of science other than those traditionally aligned to clinical medicine, like physiology or chemistry. Fascinated by the new technology of photography, Charcot created a highly sophisticated <span><span>medical photographic division</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> that included not only cameras for still photographs, but also multi-image cameras attached to a metronome to capture the</section></section><section><section><h2>Heredity as the primary etiology of neurological diseases</h2>Charcot largely assumed that heredity was the fundamental causative agent underlying primary neurological disorders. Preceding Gregor Mendell and other pioneers in the field of genetics, Charcot held firmly that his patients carried a <span><span>familial trait</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, “<em>la tache familiale neurologique.”</em> Creating genealogical trees, he insisted that he could identify neurological symptom clusters in siblings, parents, and grandparents of his patients that related directly to the cause of his patient's plight. In</section></section><section><section><h2>200 years</h2>The three pillars cited here provide a reference to a scientific legacy, but because Charcot's lectures remain available for study, his <span><span>human legacy</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> can also be appreciated. His elegantly stated advice to hi","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"54 7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00387-4
Gil D Rabinovici
No Abstract
没有抽象的
{"title":"Progress in Alzheimer's disease: The Lancet Series","authors":"Gil D Rabinovici","doi":"10.1016/s1474-4422(25)00387-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00387-4","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00350-3
Clifford R Jack, Mingzhao Hu, Heather J Wiste, David S Knopman, Prashanthi Vemuri, Jonathan Graff-Radford, Val J Lowe, Maria Vassilaki, Petrice M Cogswell, Christopher G Schwarz, Alicia Algeciras-Schimnich, Ronald C Petersen, Terry M Therneau
<h3>Background</h3>A key knowledge gap concerns the lifetime risk of developing cognitive impairment among individuals who are cognitively unimpaired with abnormal Alzheimer's disease biomarkers. Our aim was to compute lifetime and 10-year absolute risk of cognitive impairment as a function of continuous amyloid PET.<h3>Methods</h3>In this retrospective, longitudinal cohort study of data from participants of the population-based Mayo Clinic Study of Aging (Olmsted County, MN, USA), we computed lifetime and 10-year absolute risk of cognitive impairment in participants who were cognitively unimpaired and aged 50 years or older at enrolment. The primary predictor of interest was biological Alzheimer's disease severity, based on amyloid PET centiloid value. Starting age, sex, and <em>APOE</em> ε4 carriership status were also predictors. Outcomes were incident mild cognitive impairment (MCI), dementia, and death, which were ascertained or estimated via multistate hidden Markov modelling both in study and out of study.<h3>Findings</h3>Between Nov 29, 2004, and Dec 2, 2024, 5158 participants (2623 [51%] women and 2535 [49%] men) who are cognitively unimpaired and 700 (307 [44%] women and 393 [56%] men) with MCI were included for analysis. Lifetime risk of MCI and dementia increased monotonically with increasing centiloid value (p<0·0001), which was the predictor with the largest effect. Lifetime risk of MCI for male <em>APOE</em> ε4 carriers who are cognitively unimpaired at a starting age of 75 years was 56·2% (95% CI 50·5–61·9) for centiloid 5, 60·2% (54·9–65·6) for centiloid 25, 71·0% (65·2–76·7) for centiloid 50, 75·2% (69·1–81·2) for centiloid 75, and 76·5% (70·5–82·4) for centiloid 100. Lifetime risk of MCI for female <em>APOE</em> ε4 carriers who are cognitively unimpaired at a starting age of 75 years was 68·9% (63·7–74·1) for centiloid 5, 71·3% (66·6–76·0) for centiloid 25, 77·6% (72·5–82·7) for centiloid 50, 81·2% (76·7–85·7) for centiloid 75, and 83·8% (78·5–89·1) for centiloid 100. Within each centiloid group, and for both men and women, lifetime and 10-year absolute risk for MCI and dementia was greater for <em>APOE</em> ε4 carriers than for non-carriers (p<0·0001). Biological severity of Alzheimer's disease was a predictor of 10-year absolute risk of MCI and dementia (p<0·0001); however, starting age (p<0·0001) had a more prominent effect. The rate of incident dementia was two times greater among individuals who had previously left the study than those who remained in the study.<h3>Interpretation</h3>Lifetime and 10-year absolute risk for MCI and dementia among individuals who are currently cognitively unimpaired increase with increasing biological severity of Alzheimer's disease. This information should be important for risk–benefit evaluation of therapeutic interventions in the future. The high lifetime risk in participants with higher centiloid values addresses academic controversies concerning risk of future impairment asso
{"title":"Lifetime and 10-year absolute risk of cognitive impairment in relation to amyloid PET severity: a retrospective, longitudinal cohort study","authors":"Clifford R Jack, Mingzhao Hu, Heather J Wiste, David S Knopman, Prashanthi Vemuri, Jonathan Graff-Radford, Val J Lowe, Maria Vassilaki, Petrice M Cogswell, Christopher G Schwarz, Alicia Algeciras-Schimnich, Ronald C Petersen, Terry M Therneau","doi":"10.1016/s1474-4422(25)00350-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00350-3","url":null,"abstract":"<h3>Background</h3>A key knowledge gap concerns the lifetime risk of developing cognitive impairment among individuals who are cognitively unimpaired with abnormal Alzheimer's disease biomarkers. Our aim was to compute lifetime and 10-year absolute risk of cognitive impairment as a function of continuous amyloid PET.<h3>Methods</h3>In this retrospective, longitudinal cohort study of data from participants of the population-based Mayo Clinic Study of Aging (Olmsted County, MN, USA), we computed lifetime and 10-year absolute risk of cognitive impairment in participants who were cognitively unimpaired and aged 50 years or older at enrolment. The primary predictor of interest was biological Alzheimer's disease severity, based on amyloid PET centiloid value. Starting age, sex, and <em>APOE</em> ε4 carriership status were also predictors. Outcomes were incident mild cognitive impairment (MCI), dementia, and death, which were ascertained or estimated via multistate hidden Markov modelling both in study and out of study.<h3>Findings</h3>Between Nov 29, 2004, and Dec 2, 2024, 5158 participants (2623 [51%] women and 2535 [49%] men) who are cognitively unimpaired and 700 (307 [44%] women and 393 [56%] men) with MCI were included for analysis. Lifetime risk of MCI and dementia increased monotonically with increasing centiloid value (p<0·0001), which was the predictor with the largest effect. Lifetime risk of MCI for male <em>APOE</em> ε4 carriers who are cognitively unimpaired at a starting age of 75 years was 56·2% (95% CI 50·5–61·9) for centiloid 5, 60·2% (54·9–65·6) for centiloid 25, 71·0% (65·2–76·7) for centiloid 50, 75·2% (69·1–81·2) for centiloid 75, and 76·5% (70·5–82·4) for centiloid 100. Lifetime risk of MCI for female <em>APOE</em> ε4 carriers who are cognitively unimpaired at a starting age of 75 years was 68·9% (63·7–74·1) for centiloid 5, 71·3% (66·6–76·0) for centiloid 25, 77·6% (72·5–82·7) for centiloid 50, 81·2% (76·7–85·7) for centiloid 75, and 83·8% (78·5–89·1) for centiloid 100. Within each centiloid group, and for both men and women, lifetime and 10-year absolute risk for MCI and dementia was greater for <em>APOE</em> ε4 carriers than for non-carriers (p<0·0001). Biological severity of Alzheimer's disease was a predictor of 10-year absolute risk of MCI and dementia (p<0·0001); however, starting age (p<0·0001) had a more prominent effect. The rate of incident dementia was two times greater among individuals who had previously left the study than those who remained in the study.<h3>Interpretation</h3>Lifetime and 10-year absolute risk for MCI and dementia among individuals who are currently cognitively unimpaired increase with increasing biological severity of Alzheimer's disease. This information should be important for risk–benefit evaluation of therapeutic interventions in the future. The high lifetime risk in participants with higher centiloid values addresses academic controversies concerning risk of future impairment asso","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"148 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00404-1
Joseph Yaria, Sebastian F Winter, Gregory Roth, Volker Hömberg, Thomas Platz, Mayowa O Owolabi
No Abstract
没有抽象的
{"title":"Announcing The Lancet Neurology Commission on Neurorehabilitation","authors":"Joseph Yaria, Sebastian F Winter, Gregory Roth, Volker Hömberg, Thomas Platz, Mayowa O Owolabi","doi":"10.1016/s1474-4422(25)00404-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00404-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00394-1
Zhang C, Zhang M, Qui W, et al. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol 2020; 19: 391–401—In the Declaration of interest section of this Article, statements have been corrected for Fu-Dong-Shi. These corrections have been made to the online version as of Nov 12, 2025.
{"title":"Correction to Lancet Neurol 2020; 19: 391–401","authors":"","doi":"10.1016/s1474-4422(25)00394-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00394-1","url":null,"abstract":"<em>Zhang C, Zhang M, Qui W, et al. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.</em> Lancet Neurol <em>2020; <strong>19:</strong> 391–401</em>—In the Declaration of interest section of this Article, statements have been corrected for Fu-Dong-Shi. These corrections have been made to the online version as of Nov 12, 2025.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"148 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00405-3
Giovanni B Frisoni, Augusto J Mendes
No Abstract
没有抽象的
{"title":"Brain amyloid on the way to dementia prevention","authors":"Giovanni B Frisoni, Augusto J Mendes","doi":"10.1016/s1474-4422(25)00405-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00405-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"378 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/s1474-4422(25)00383-7
Chung-Wei Christine Lin, Chris G Maher, Richard O Day
No Abstract
没有抽象的
{"title":"Caution on the use of α2δ-ligands in neuropathic pain","authors":"Chung-Wei Christine Lin, Chris G Maher, Richard O Day","doi":"10.1016/s1474-4422(25)00383-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00383-7","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"182 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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