المؤلفون: Nina Possemis, Frans Verhey, Jos Prickaerts, Arjan Blokland, Inez Ramakers

المصدر: Trials, Vol 25, Iss 1, Pp 1-20 (2024)

مصطلحات موضوعية: Mild cognitive impairment, Dementia, Alzheimer, Cognitive dysfunction, Roflumilast, Phosphodiesterase 4, Medicine (General), R5-920

الوصف: Abstract Background Research into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer’s disease (AD) dementia. Methods The study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 μg roflumilast, and 100 μg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants’ performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants. Discussion The outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders. Trial registration The Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NLTest ) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1Test ) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1745-6215Test

الوصول الحر: https://doaj.org/article/cd69a97d690d460aa9bb2a284f8a4f61Test

المؤلفون: Daphne ter Huurne, Nina Possemis, Leonie Banning, Angélique Gruters, Alexandra König, Nicklas Linz, Johannes Tröger, Kai Langel, Frans Verhey, Marjolein de Vugt, Inez Ramakers

المصدر: Digital Biomarkers, Vol 7, Iss 1, Pp 115-123 (2023)

مصطلحات موضوعية: phone assessment, automated speech analysis, mild cognitive impairment, memory, fluency, Biology (General), QH301-705.5

الوصف: Introduction: We studied the accuracy of the automatic speech recognition (ASR) software by comparing ASR scores with manual scores from a verbal learning test (VLT) and a semantic verbal fluency (SVF) task in a semiautomated phone assessment in a memory clinic population. Furthermore, we examined the differentiating value of these tests between participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We also investigated whether the automatically calculated speech and linguistic features had an additional value compared to the commonly used total scores in a semiautomated phone assessment. Methods: We included 94 participants from the memory clinic of the Maastricht University Medical Center+ (SCD N = 56 and MCI N = 38). The test leader guided the participant through a semiautomated phone assessment. The VLT and SVF were audio recorded and processed via a mobile application. The recall count and speech and linguistic features were automatically extracted. The diagnostic groups were classified by training machine learning classifiers to differentiate SCD and MCI participants. Results: The intraclass correlation for inter-rater reliability between the manual and the ASR total word count was 0.89 (95% CI 0.09–0.97) for the VLT immediate recall, 0.94 (95% CI 0.68–0.98) for the VLT delayed recall, and 0.93 (95% CI 0.56–0.97) for the SVF. The full model including the total word count and speech and linguistic features had an area under the curve of 0.81 and 0.77 for the VLT immediate and delayed recall, respectively, and 0.61 for the SVF. Conclusion: There was a high agreement between the ASR and manual scores, keeping the broad confidence intervals in mind. The phone-based VLT was able to differentiate between SCD and MCI and can have opportunities for clinical trial screening.

وصف الملف: electronic resource

العلاقة: https://beta.karger.com/Article/FullText/533188Test; https://doaj.org/toc/2504-110XTest

الوصول الحر: https://doaj.org/article/57b076a8e51c43649c2884ed3a575440Test

المؤلفون: Dariia Yosypyshyn, Domantė Kučikienė, Inez Ramakers, Jörg B. Schulz, for the Alzheimer’s Disease Neuroimaging Initiative, Kathrin Reetz, Ana Sofia Costa

المصدر: Neurological Research and Practice, Vol 5, Iss 1, Pp 1-11 (2023)

مصطلحات موضوعية: Alzheimer’s disease, Cognitive impairment, Memory clinic, ATN, Biomarkers, Validation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Background The AT(N) research framework for Alzheimer's disease (AD) remains unclear on how to best deal with borderline cases. Our aim was to characterise patients with suspected AD with a borderline Aß1-42/Aß1-40 ratio in cerebrospinal fluid. Methods We analysed retrospective data from two cohorts (memory clinic cohort and ADNI) of patients (n = 63) with an Aß1-42/Aß1-40 ratio within a predefined borderline area—Q1 above the validated cut-off value(grey zone). We compared demographic, clinical, neuropsychological and neuroimaging features between grey zone patients and patients with low Aß1-42 (normal Aß ratio but pathological Aß1-42, n = 42) and patients with AD (pathological Aß, P-Tau, und T-Tau, n = 80). Results Patients had mild cognitive impairment or mild dementia and a median age of 72 years. Demographic and general clinical characteristics did not differ between the groups. Patients in the grey zone group were the least impaired in cognition. However, they overlapped with the low Aß1-42 group in verbal episodic memory performance, especially in delayed recall and recognition. The grey zone group had less severe medial temporal atrophy, but mild posterior atrophy and mild white matter hyperintensities, similar to the low Aß1-42 group. Conclusions Patients in the Aß ratio grey zone were less impaired, but showed clinical overlap with patients on the AD continuum. These borderline patients may be at an earlier disease stage. Assuming an increased risk of AD and progressive cognitive decline, careful consideration of clinical follow-up is recommended when using dichotomous approaches to classify Aß status.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2524-3489Test

الوصول الحر: https://doaj.org/article/a204332cd2d44f14a28bfff3d82d789cTest

المؤلفون: Johannes Tröger, Ebru Baykara, Jian Zhao, Daphne ter Huurne, Nina Possemis, Elisa Mallick, Simona Schäfer, Louisa Schwed, Mario Mina, Nicklas Linz, Inez Ramakers, Craig Ritchie

المصدر: Digital Biomarkers, Vol 6, Iss 3, Pp 107-116 (2022)

مصطلحات موضوعية: mild cognitive impairment, digital biomarker, speech biomarker, dementia, speech analysis, clinical trials, Biology (General), QH301-705.5

الوصف: Introduction: Progressive cognitive decline is the cardinal behavioral symptom in most dementia-causing diseases such as Alzheimer’s disease. While most well-established measures for cognition might not fit tomorrow’s decentralized remote clinical trials, digital cognitive assessments will gain importance. We present the evaluation of a novel digital speech biomarker for cognition (SB-C) following the Digital Medicine Society’s V3 framework: verification, analytical validation, and clinical validation. Methods: Evaluation was done in two independent clinical samples: the Dutch DeepSpA (N = 69 subjective cognitive impairment [SCI], N = 52 mild cognitive impairment [MCI], and N = 13 dementia) and the Scottish SPeAk datasets (N = 25, healthy controls). For validation, two anchor scores were used: the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) scale. Results: Verification: The SB-C could be reliably extracted for both languages using an automatic speech processing pipeline. Analytical Validation: In both languages, the SB-C was strongly correlated with MMSE scores. Clinical Validation: The SB-C significantly differed between clinical groups (including MCI and dementia), was strongly correlated with the CDR, and could track the clinically meaningful decline. Conclusion: Our results suggest that the ki:e SB-C is an objective, scalable, and reliable indicator of cognitive decline, fit for purpose as a remote assessment in clinical early dementia trials.

وصف الملف: electronic resource

العلاقة: https://www.karger.com/Article/FullText/526471Test; https://doaj.org/toc/2504-110XTest

الوصول الحر: https://doaj.org/article/d715274c09c14aa5807f9200f2c82a8fTest

المؤلفون: Radia Zeghari, Rachid Guerchouche, Minh Tran-Duc, François Bremond, Kai Langel, Inez Ramakers, Nathalie Amiel, Maria Pascale Lemoine, Vincent Bultingaire, Valeria Manera, Philippe Robert, Alexandra König

المصدر: Diagnostics; Volume 12; Issue 4; Pages: 925

مصطلحات موضوعية: telemedicine, cognitive testing, dementia, teleneuropsychology, neuropsychology

الوصف: Today, in rural isolated areas or so-called ‘medical deserts’, access to diagnosis and care is very limited. With the current pandemic crisis, now even more than ever, telemedicine platforms are gradually more employed for remote medical assessment. Only a few are tailored to comprehensive teleneuropsychological assessment of older adults. Hence, our study focuses on evaluating the feasibility of performing a remote neuropsychological assessment of older adults suffering from a cognitive complaint. 50 participants (aged 55 and older) were recruited at the local hospital of Digne-les-Bains, France. A brief neuropsychological assessment including a short clinical interview and several validated neuropsychological tests was administered in two conditions, once by Teleneuropsychology (TNP) and once by Face-to-Face (FTF) in a crossover design. Acceptability and user experience was assessed through questionnaires. Results show high agreement in most tests between the FTF and TNP conditions. The TNP was overall well accepted by the participants. However, differences in test performances were observed, which urges the need to validate TNP tests with broader samples with normative data.

وصف الملف: application/pdf

العلاقة: Point-of-Care Diagnostics and Devices; https://dx.doi.org/10.3390/diagnostics12040925Test

الإتاحة: https://doi.org/10.3390/diagnostics12040925Test

المؤلفون: Philippe Robert, Alexandra König, Radia Zeghari, Rachid Guerchouche, Minh Duc Tran, François Bremond, Nicklas Linz, Hali Lindsay, Kai Langel, Inez Ramakers, Pascale Lemoine, Vincent Bultingaire

المصدر: BMJ Open, Vol 11, Iss 9 (2021)

مصطلحات موضوعية: Medicine

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/11/9/e047083.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/13f878cad9eb4100bfbbd5566152901aTest

المؤلفون: Simona, Schäfer, Elisa, Mallick, Louisa, Schwed, Alexandra, König, Jian, Zhao, Nicklas, Linz, Timothy Hadarsson, Bodin, Johan, Skoog, Nina, Possemis, Daphne, Ter Huurne, Anna, Zettergren, Silke, Kern, Simona, Sacuiu, Inez, Ramakers, Ingmar, Skoog, Johannes, Tröger

المساهمون: RS: MHeNs - R3 - Neuroscience, Basic Neuroscience 2, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychology 1, Psychology 2

المصدر: Journal of Alzheimer's Disease, 91(3), 1165-1171. IOS Press

مصطلحات موضوعية: Psychiatry and Mental health, Clinical Psychology, General Neuroscience, General Medicine, Geriatrics and Gerontology

الوصف: BACKGROUND: Modern prodromal Alzheimer's disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed.OBJECTIVE: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations.METHODS: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (N = 121) and a Swedish birth cohort (N = 404). MCI classification was each evaluated on the training cohort as well as across on the unrelated validation cohort.RESULTS: The algorithms achieved a performance of AUC 0.73 and AUC 0.77 in the respective training cohorts and AUC 0.81 in the unseen validation cohort.CONCLUSION: The results indicate that a ki:e SB-C based algorithm robustly detects MCI across different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::309dee186fd0b3643ecb8375d6ea4d0fTest
https://doi.org/10.3233/jad-220762Test

المؤلفون: Aurore Delvenne, Johan Gobom, Betty Tijms, Isabelle Bos, Lianne M. Reus, Valerija Dobricic, Mara ten Kate, Frans Verhey, Inez Ramakers, Philip Scheltens, Charlotte E. Teunissen, Rik Vandenberghe, Jolien Schaeverbeke, Silvy Gabel, Julius Popp, Gwendoline Peyratout, Pablo Martinez‐Lage, Mikel Tainta, Magda Tsolaki, Yvonne Freund‐Levi, Simon Lovestone, Johannes Streffer, Frederik Barkhof, Lars Bertram, Kaj Blennow, Henrik Zetterberg, Pieter Jelle Visser, Stephanie J. B. Vos

المساهمون: Neurology, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Clinical chemistry, Amsterdam Neuroscience - Neuroinfection & -inflammation, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychology 6, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Psychology 2

المصدر: Alzheimer's & dementia
Delvenne, A, Gobom, J, Tijms, B, Bos, I, Reus, L M, Dobricic, V, Kate, M T, Verhey, F, Ramakers, I, Scheltens, P, Teunissen, C E, Vandenberghe, R, Schaeverbeke, J, Gabel, S, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Tsolaki, M, Freund-Levi, Y, Lovestone, S, Streffer, J, Barkhof, F, Bertram, L, Blennow, K, Zetterberg, H, Visser, P J & Vos, S J B 2022, ' Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiology ', Alzheimer's and Dementia . https://doi.org/10.1002/alz.12713Test
Alzheimer's and Dementia. Elsevier
Alzheimer's & Dementia, 19(3), 807-820. Elsevier Science

مصطلحات موضوعية: Epidemiology, Clinical Neurology, PROTEIN, behavioral disciplines and activities, cerebrospinal fluid, Cellular and Molecular Neuroscience, mild cognitive impairment, proteomics, ADULT, Developmental Neuroscience, mental disorders, tau, pathophysiology, Science & Technology, suspected non-Alzheimer's disease pathophysiology, Health Policy, biomarkers, Alzheimer's disease, nervous system diseases, Psychiatry and Mental health, Neurosciences & Neurology, Human medicine, Neurology (clinical), Geriatrics and Gerontology, Life Sciences & Biomedicine, human activities

الوصف: BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics. METHODS: Individuals were classified based on CSF amyloid beta (Aβ)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed. RESULTS: A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus. CONCLUSION: The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD. ispartof: ALZHEIMERS & DEMENTIA vol:19 issue:3 pages:807-820 ispartof: location:United States status: published

وصف الملف: Print-Electronic

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f0cefafaf25dc245841c892465ac470Test
https://doi.org/10.1002/alz.12713Test

المؤلفون: Ron Handels, Sabine Grimm, Arjan Blokland, Nina Possemis, Inez Ramakers, Anke Sambeth, Frans Verhey, Stephanie Vos, Manuela Joore, Jos Prickaerts, Linus Jönsson

المساهمون: Psychology 2, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: KIO Kemta (9), Section Psychopharmacology, RS: FPN NPPP II, Basic Neuroscience 2, RS: MHeNs - R3 - Neuroscience, Sect. Teaching & Innovation of Learning, RS: FPN STIL, Psychiatrie & Neuropsychologie, RS: CAPHRI - R2 - Creating Value-Based Health Care

المصدر: Alzheimer's & Dementia. Elsevier Science

مصطلحات موضوعية: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology

الوصف: INTRODUCTION: Early health-technology assessment can support discussing scarce resource allocation among stakeholders. We explored the value of maintaining cognition in patients with mild cognitive impairment (MCI) by estimating: (1) the innovation headroom and (2) the potential cost effectiveness of roflumilast treatment in this population.METHODS: The innovation headroom was operationalized by a fictive 100% efficacious treatment effect, and the roflumilast effect on memory word learning test was assumed to be associated with 7% relative risk reduction of dementia onset. Both were compared to Dutch setting usual care using the adapted International Pharmaco-Economic Collaboration on Alzheimer's Disease (IPECAD) open-source model.RESULTS: The total innovation headroom expressed as net health benefit was 4.2 (95% bootstrap interval: 2.9-5.7) quality-adjusted life years (QALYs). The potential cost effectiveness of roflumilast was k€34 per QALY.DISCUSSION: The innovation headroom in MCI is substantial. Although the potential cost effectiveness of roflumilast treatment is uncertain, further research on its effect on dementia onset is likely valuable.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d8b39cafdcd89be3cabc74620d81b09cTest
https://doi.org/10.1002/alz.13001Test

المؤلفون: Daphne ter Huurne, Inez Ramakers, Nina Possemis, Leonie Banning, Angelique Gruters, Stephanie Van Asbroeck, Alexandra König, Nicklas Linz, Johannes Tröger, Kai Langel, Frans Verhey, Marjolein de Vugt

المصدر: Archives of Clinical Neuropsychology.

مصطلحات موضوعية: MILD COGNITIVE IMPAIRMENT, NORMATIVE DATA, EDUCATION, General Medicine, PERFORMANCE, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Clinical Psychology, VERBAL FLUENCY, Neuropsychology and Physiological Psychology, AGE, Cognitive dysfunction, PARKINSONS-DISEASE, Neuropsychological tests, TESTS, Speech, PARTICIPANTS, Alzheimer disease

الوصف: Objective To investigate whether automatic analysis of the Semantic Verbal Fluency test (SVF) is reliable and can extract additional information that is of value for identifying neurocognitive disorders. In addition, the associations between the automatically derived speech and linguistic features and other cognitive domains were explored. Method We included 135 participants from the memory clinic of the Maastricht University Medical Center+ (with Subjective Cognitive Decline [SCD; N = 69] and Mild Cognitive Impairment [MCI]/dementia [N = 66]). The SVF task (one minute, category animals) was recorded and processed via a mobile application, and speech and linguistic features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to differentiate SCD and MCI/dementia participants. Results The intraclass correlation for interrater reliability between the clinical total score (golden standard) and automatically derived total word count was 0.84. The full model including the total word count and the automatically derived speech and linguistic features had an Area Under the Curve (AUC) of 0.85 for differentiating between people with SCD and MCI/dementia. The model with total word count only and the model with total word count corrected for age showed an AUC of 0.75 and 0.81, respectively. Semantic switching correlated moderately with memory as well as executive functioning. Conclusion The one-minute SVF task with automatically derived speech and linguistic features was as reliable as the manual scoring and differentiated well between SCD and MCI/dementia. This can be considered as a valuable addition in the screening of neurocognitive disorders and in clinical practice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::449c9b2306b9d3201b0e91f334358209Test
https://doi.org/10.1093/arclin/acac105Test