Neurodegenerative Diseases最新文献

{"title":"White Matter Hyperintensities Are Associated with Slower Gait Speed in Older Adults without Dementia.","authors":"Juan P Vazquez, Joe Verghese, Nir Barzilai, Sofiya Milman, Helena M Blumen","doi":"10.1159/000538944","DOIUrl":"10.1159/000538944","url":null,"abstract":"<p><strong>Introduction: </strong>Slow gait speed is associated with poor health outcomes in aging, but the relationship between cerebral small vessel disease (CSVD) pathologies and gait speed in aging is not well understood. We investigated the relationships between CSVD imaging markers and gait speed during simple (normal pace walking [NPW]) and complex (walking while talking [WWT]) as both measures are associated with shared health outcomes such as falls, frailty, disability, mortality, and dementia.</p><p><strong>Methods: </strong>A total of 113 Ashkenazi Jewish adults over 65 (M age = 78.6 ± 6.3 years, 45.8% women) and without dementia were examined. Established rating systems were used to quantify white matter hyperintensities (WMHs) and lacunes of presumed vascular origin from fluid-attenuated inversion recovery (FLAIR) images. Linear regression models adjusted for age, sex, global health, and total intracranial volume were used to examine associations between CSVD markers and gait speed during NPW and WWT. Student t tests were used to contrast gait speed in those with \"confluent-diffuse\" WMH and those with \"mild or no\" WMH.</p><p><strong>Results: </strong>The number of WMH in the basal ganglia (β = -3.274 cm/s p = 0.047) and temporal lobes (β = -3.113 cm/s p = 0.048) were associated with slower NPW speed in adjusted models. Participants with higher CSVD burden (confluent-diffuse pattern) in the frontal lobe (94.65 cm/s vs. 105.21 cm/s, p = 0.018) and globally (98.98 cm/s vs. 107.24 cm/s, p = 0.028) also had lower NPW speed. WMHs were not associated with WWT speeds. Lacunes were not associated with NPW or WWT speed.</p><p><strong>Conclusion: </strong>Adjusted models found higher CSVD burden as measured by the presence of WMH in the basal ganglia and temporal lobes were associated with slower normal pace gait speed in older adults, but not with complex walking speeds. Participants with confluent-diffuse WMHs in the frontal lobes were found to have slower average normal gait speed. Further studies are needed to establish the temporality of WMH and gait speed decline as well as mechanistic links between the two.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Biomarkers for Alzheimer's Disease: Unlocking the Diagnostic Potential in Low- and Middle-Income Countries, Focusing on Africa.","authors":"Luc Nwamekang Belinga, Jeanne Espourteille, Yembe Wepnyu Njamnshi, Ariole Zafack Zeukang, Olivier Rouaud, Alfred Kongnyu Njamnshi, Gilles Allali, Kevin Richetin","doi":"10.1159/000538623","DOIUrl":"10.1159/000538623","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is emerging as a significant public health challenge in Africa, with predictions indicating a tripling in incidence by 2050. The diagnosis of AD on the African continent is notably difficult, leading to late detection that severely limits treatment options and significantly impacts the quality of life for patients and their families.</p><p><strong>Summary: </strong>This review focuses on the potential of high-sensitivity specific blood biomarkers as promising tools for improving AD diagnosis and management globally, particularly in Africa. These advances are particularly pertinent in the continent, where access to medical and technical resources is often limited.</p><p><strong>Key messages: </strong>Identifying precise, sensitive, and specific blood biomarkers could contribute to the biological characterization and management of AD in Africa. Such advances promise to improve patient care and pave the way for new regional opportunities in pharmaceutical research and drug trials on the continent for AD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"26-40"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20th Anniversary of Neurodegenerative Diseases: A Parallel (R)Evolution between the 20th and the 21st Century?","authors":"Gilles Allali","doi":"10.1159/000539440","DOIUrl":"10.1159/000539440","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"2-5"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Drug Interactions on the Results of DAT-SPECT Imaging in a Specialty Movement Disorders Practice: A Retrospective Analysis of Outcomes.","authors":"Isabelle Heewon Kang, Danny Bega","doi":"10.1159/000540105","DOIUrl":"10.1159/000540105","url":null,"abstract":"<p><strong>Introduction: </strong>DAT-SPECT imaging is approved as a diagnostic tool for the evaluation of suspected Parkinsonian syndromes, but the FDA-approved package insert lists 16 potential drugs that may interfere with the image obtained. The clinical impact of these drugs on imaging results has not been established. This study aimed to determine the accuracy of DAT-SPECT imaging in assessing presynaptic dopaminergic denervation in the setting of these drugs.</p><p><strong>Methods: </strong>This is a retrospective chart review of patients at a single center who underwent DAT-SPECT imaging while taking \"contraindicated\" drugs between December 2012 and December 2022.</p><p><strong>Results: </strong>A total of 1,224 charts were screened, and 153 (12.5%) charts met the inclusion criteria. Bupropion (32%, n = 49) and sertraline (26%, n = 40) were the most common contraindicated drugs. The false-positive rate was 9.2%.</p><p><strong>Conclusion: </strong>This retrospective analysis supports the concern that certain drugs may interfere with DAT-SPECT imaging results, leading to potential false positives. This has implications for how clinicians interpret DAT-SPECT imaging in patients taking these medications and whether they should advise patients to stop these medications before a scan is performed.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"91-96"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of Mild Cognitive Impairment and Alzheimer's Disease Using Manual Motor Measures.","authors":"Vincent Koppelmans, Marit F L Ruitenberg, Sydney Y Schaefer, Jace B King, Jasmine M Jacobo, Benjamin P Silvester, Amanda F Mejia, Jos van der Geest, John M Hoffman, Tolga Tasdizen, Kevin Duff","doi":"10.1159/000539800","DOIUrl":"10.1159/000539800","url":null,"abstract":"<p><strong>Introduction: </strong>Manual motor problems have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the specific aspects that are affected, their neuropathology, and potential value for classification modeling is unknown. The current study examined if multiple measures of motor strength, dexterity, and speed are affected in MCI and AD, related to AD biomarkers, and are able to classify MCI or AD.</p><p><strong>Methods: </strong>Fifty-three cognitively normal (CN), 33 amnestic MCI, and 28 AD subjects completed five manual motor measures: grip force, Trail Making Test A, spiral tracing, finger tapping, and a simulated feeding task. Analyses included (1) group differences in manual performance; (2) associations between manual function and AD biomarkers (PET amyloid β, hippocampal volume, and APOE ε4 alleles); and (3) group classification accuracy of manual motor function using machine learning.</p><p><strong>Results: </strong>Amnestic MCI and AD subjects exhibited slower psychomotor speed and AD subjects had weaker dominant hand grip strength than CN subjects. Performance on these measures was related to amyloid β deposition (both) and hippocampal volume (psychomotor speed only). Support vector classification well-discriminated control and AD subjects (area under the curve of 0.73 and 0.77, respectively) but poorly discriminated MCI from controls or AD.</p><p><strong>Conclusion: </strong>Grip strength and spiral tracing appear preserved, while psychomotor speed is affected in amnestic MCI and AD. The association of motor performance with amyloid β deposition and atrophy could indicate that this is due to amyloid deposition in and atrophy of motor brain regions, which generally occurs later in the disease process. The promising discriminatory abilities of manual motor measures for AD emphasize their value alongside other cognitive and motor assessment outcomes in classification and prediction models, as well as potential enrichment of outcome variables in AD clinical trials.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"54-70"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole Exome Sequencing Indicating GGCCTG Hexanucleotide Repeat in Patients with Spinocerebellar Ataxia Type 36.","authors":"Ran Chen, Chao Zhou, Yun Peng, Pengcheng Huang, Yanyan Yu, Min Zhu, Meihong Zhou, Daojun Hong, Dandan Tan","doi":"10.1159/000540006","DOIUrl":"10.1159/000540006","url":null,"abstract":"<p><strong>Introduction: </strong>Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients.</p><p><strong>Methods: </strong>Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot.</p><p><strong>Results: </strong>GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1,390-1,556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles.</p><p><strong>Conclusion: </strong>The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"71-79"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Taxonomy of Subjective Cognitive Decline: Proposal and First Clinical Evidence from the Geneva Memory Clinic Cohort.","authors":"Federica Ribaldi, Rafael Palomo, Daniele Altomare, Max Scheffler, Frederic Assal, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Marc Abramowicz, Valentina Garibotto, Christian Chicherio, Giovanni B Frisoni","doi":"10.1159/000539053","DOIUrl":"10.1159/000539053","url":null,"abstract":"<p><strong>Introduction: </strong>Subjective cognitive decline (SCD) is characterized by subjective cognitive concerns without objective cognitive impairment and is considered a risk factor for cognitive decline and dementia. However, most SCD patients will not develop neurodegenerative disorders, yet they may suffer from minor psychiatric, neurological, or somatic comorbidities. The aim of the present study was to provide a taxonomy of the heterogeneous SCD entity and to conduct a preliminary validation using data from a memory clinic sample.</p><p><strong>Methods: </strong>Participants were fifty-five SCD individuals consecutively recruited at the Geneva Memory Center. Based on clinical reports, they were classified into three clinically pre-defined subgroups: (i) those with psychological or psychiatric comorbidities (Psy), (ii) those with somatic comorbidities (SomCom), (iii) and those with no apparent cause (NAC). Baseline demographics, clinical, cognitive, and biomarker differences among the SCD subgroups were assessed. Longitudinal cognitive changes (average 3 years follow-up) were modeled using a linear mixed model.</p><p><strong>Results: </strong>Out of the 55 SCD cases, 16 were SomCom, 18 Psy, and 21 NAC. 47% were female, mean age was 71 years. We observed higher frequency of APOE ε4 carriers in NAC (53%) compared to SomCom (14%) and Psy (0%, p = 0.023) and lower level of plasma Aβ42 in NAC (6.8 ± 1.0) compared to SomCom (8.4 ± 1.1; p = 0.031). SomCom subjects were older (74 years) than Psy (67 years, p = 0.011), and had greater medial temporal lobe atrophy (1.0 ± 1.0) than Psy (0.2 ± 0.6) and NAC (0.4 ± 0.5, p = 0.005). SomCom has worse episodic memory performances (14.5 ± 3.5) than Psy (15.8 ± 0.4) and NAC (15.8 ± 0.7, p = 0.032). We observed a slightly steeper, yet not statistically significant, cognitive decline in NAC (β = -0.48) compared to Psy (β = -0.28) and SomCom (β = -0.24).</p><p><strong>Conclusions: </strong>NAC features a higher proportion of APOE ε4 carriers, lower plasma Aβ42 and a trend towards steeper cognitive decline than SomCom and Psy. Taken together, these findings suggest that NACs are at higher risk of cognitive decline due to AD. The proposed clinical taxonomy might be implemented in clinical practice to identify SCD at higher risk. However, such taxonomy should be tested on an independent cohort with a larger sample size.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"16-25"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subjective Sleep Disturbance and Lewy Pathology: Data from a Cohort of Essential Tremor Brain Donors.","authors":"Ali Ghanem, Diane S Berry, Stephanie Cosentino, Phyllis L Faust, Elan D Louis","doi":"10.1159/000539032","DOIUrl":"10.1159/000539032","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases.</p><p><strong>Methods: </strong>Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last - first), and LP on postmortem brain examination.</p><p><strong>Results: </strong>ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last - first sleep latency component score) was associated with presence of LP on postmortem brain examination - greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04).</p><p><strong>Conclusion: </strong>In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"6-15"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XXXth Congress of Société Francophone Posture Equilibre et Locomotion, Paris, France, 5-6 December 2024 - Abstracts.","authors":"","doi":"10.1159/000542208","DOIUrl":"10.1159/000542208","url":null,"abstract":"<p><p>n/a.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"24 Suppl 1","pages":"1-61"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Decision-Making Algorithm for Remote Digital Assessments of Alzheimer's Disease.","authors":"Valeria Manera, Clair Vandersteen, Alexandra Plonka, Constance Lafontaine, Kevin Galery, Alexandre Derreumaux, Nouha Ben Gaied, Aurélie Mouton, Guillaume Sacco, Cyrille Launay, Olivier Guérin, Philippe Robert, Gilles Allali, Kim Sawchuk, Olivier Beauchet, Auriane Gros","doi":"10.1159/000539129","DOIUrl":"10.1159/000539129","url":null,"abstract":"<p><strong>Introduction: </strong>Remote digital assessments (RDAs) such as voice recording, video and motor sensors, olfactory, hearing, and vision screenings are now starting to be employed to complement classical biomarker and clinical evidence to identify patients in the early AD stages. Choosing which RDA can be proposed to individual patients is not trivial and often time-consuming. This position paper presents a decision-making algorithm for using RDA during teleconsultations in memory clinic settings.</p><p><strong>Method: </strong>The algorithm was developed by an expert panel following the Delphi methodology.</p><p><strong>Results: </strong>The decision-making algorithm is structured as a series of yes-no questions. The resulting questionnaire is freely available online.</p><p><strong>Discussion: </strong>We suggest that the use of screening questionnaires in the context of memory clinics may help accelerating the adoption of RDA in everyday clinical practice.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"41-44"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}