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Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer’s disease

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dc.contributor.author Vöglein, Jonathan
dc.contributor.author Paumier, Katrina
dc.contributor.author Jucker, Mathias
dc.contributor.author Preische, Oliver
dc.contributor.author McDade, Eric
dc.contributor.author Hassenstab, Jason
dc.contributor.author Benzinger, Tammie L.S.
dc.contributor.author Noble, James M.
dc.contributor.author Berman, Sarah B.
dc.contributor.author Graff-Radford, Neill R.
dc.contributor.author Ghetti, Bernardino
dc.contributor.author Farlow, Martin R.
dc.contributor.author Chhatwal, Jasmeer P.
dc.contributor.author Salloway, Stephen
dc.contributor.author Xiong, Chengjie
dc.contributor.author Karch, Celeste M.
dc.contributor.author Cairns, Nigel
dc.contributor.author Mori, Hiroshi
dc.contributor.author Schofield, Peter R.
dc.contributor.author Masters, Colin L.
dc.contributor.author Goate, Alison M.
dc.contributor.author Buckles, Virginia
dc.contributor.author Fox, Nick C.
dc.contributor.author Rossor, Martin N.
dc.contributor.author Chrem Méndez, Patricio Alexis
dc.contributor.author Allegri, Ricardo Francisco
dc.contributor.author Ringman, John M.
dc.contributor.author Höglinger, Günter U.
dc.contributor.author Steiner, Harald
dc.contributor.author Dieterich, Marianne
dc.contributor.author Haass, Christian
dc.contributor.author Laske, Christoph
dc.contributor.author Morris, John C.
dc.contributor.author Bateman, Randall J.
dc.contributor.author Danek, Adrian
dc.contributor.author Levin, Johannes
dc.contributor.author Dominantly Inherited Alzheimer Network
dc.date.accessioned 2020-10-21T14:21:14Z
dc.date.available 2020-10-21T14:21:14Z
dc.date.issued 2019-03-20
dc.identifier.citation Vöglein, J., Paumier, K., Jucker, M., Preische, O., McDade, E., Hassenstab, J., Benzinger, T.L., Noble, J.M., Berman, S.B., Graff-Radford, N.R., Ghetti, B., Farlow, M.R., Chhatwal, J., Salloway, S., Xiong, C., Karch, C.M., Cairns, N., Mori, H., Schofield, P.R., Masters, C.L., Goate, A., Buckles, V., Fox, N., Rossor, M., Chrem, P., Allegri, R., Ringman, J.M., Höglinger, G., Steiner, H., Dieterich, M., Haass, C., Laske, C., Morris, J.C., Bateman, R.J., Danek, A., Levin, J. Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer’s disease. Brain 2019;142(5):1429–1440. doi:10.1093/brain/awz050 en_US
dc.identifier.uri https://doi.org/10.1093/brain/awz050
dc.identifier.uri https://repositorio.fleni.org.ar/handle/123456789/207
dc.description.abstract Owing to an early and marked deposition of amyloid-β in the basal ganglia, autosomal dominant Alzheimer’s disease could distinctly involve motor symptoms. Therefore, we aimed to assess the prevalence and characteristics of motor signs in autosomal dominant Alzheimer’s disease. Baseline Unified Parkinson Disease Rating Scale part three scores (UPDRS-III) from 433 participants of the Dominantly Inherited Alzheimer’s Network observational study were analysed. Motor symptoms were scrutinized with respect to associations with mutation carrier status, mutation site within PSEN1, basal ganglia amyloid-β as measured by Pittsburgh compound B PET, estimated years to symptom onset and Clinical Dementia Rating Scale-Sum of Boxes. Motor findings in mutation carriers were compared to patients with sporadic Alzheimer’s disease using data of the National Alzheimer’s Coordination Center. Mutation carriers showed motor findings at a higher frequency (28.4% versus 12.8%; P < 0.001) and severity (mean UPDRS-III scores 2.0 versus 0.4; P < 0.001) compared to non-carriers. Eleven of the 27 UPDRS-III items were statistically more frequently affected in mutation carriers after adjustment for multiple comparisons. Ten of these 11 items were subscale components of bradykinesia. In cognitively asymptomatic mutation carriers, dysdiadochokinesia was more frequent compared to non-carriers (right hand: 3.8% versus 0%; adjusted P = 0.023; left: 4.4% versus 0.6%; adjusted P = 0.031). In this cohort, the positive predictive value for mutation carrier status in cognitively asymptomatic participants (50% a priori risk) of dysdiadochokinesia was 100% for the right and 87.5% for the left side. Mutation carriers with motor findings more frequently were basal ganglia amyloid-β positive (84% versus 63.3%; P = 0.006) and showed more basal ganglia amyloid-β deposition (Pittsburgh compound B-standardized uptake value ratio 2.472 versus 1.928; P = 0.002) than those without. Frequency and severity of motor findings were greater in post-codon 200 PSEN1 mutations (36%; mean UPDRS-III score 3.03) compared to mutations pre-codon 200 PSEN1 (19.3%, P = 0.022; 0.91, P = 0.013). In mutation carriers, motor symptom severity was significantly positively correlated with basal ganglia amyloid-β deposition, Clinical Dementia Rating scores and estimated years to symptom onset. Mutation carriers with a Clinical Dementia Rating global score of 2 exhibited more pronounced motor symptoms than sporadic Alzheimer’s disease patients with the same Clinical Dementia Rating global score (mean UPDRS-III scores 20.71 versus 5.96; P < 0.001). With a prevalence of approximately 30% and increasing severity with progression of dementia, motor symptoms are proven as a clinically relevant finding in autosomal dominant Alzheimer’s disease, in particular in advanced dementia stages, that correlates with deposition of amyloid-β in the basal ganglia. In a very small per cent of cognitively asymptomatic members of families with autosomal dominant Alzheimer’s disease, dysdiadochokinesia may increase the chance of an individual’s status as mutation carrier. en_US
dc.language.iso eng en_US
dc.publisher Oxford en_US
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Alzheimer Disease en_US
dc.subject Enfermedad de Alzheimer en_US
dc.subject Genetics en_US
dc.subject Genética en_US
dc.title Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer’s disease en_US
dc.type info:eu-repo/semantics/publishedVersion
dc.type info:eu-repo/semantics/article en_US
dc.description.fil Fil: Vöglein, Jonathan. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Paumier, Katrina. Washington University School of Medicine; Estados Unidos
dc.description.fil Fil: Jucker, Mathias. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Preische, Oliver. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: McDade, Eric. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Hassenstab, Jason. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Benzinger, Tammie L.S. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Noble, James M. Columbia University Irving Medical Center; Estados Unidos.
dc.description.fil Fil: Berman, Sarah B. University of Pittsburgh; Estados Unidos.
dc.description.fil Fil: Graff-Radford, Neill R. Mayo Clinic; Estados Unidos.
dc.description.fil Fil: Ghetti, Bernardino. Indiana University School of Medicine; Estados Unidos.
dc.description.fil Fil: Farlow, Martin R. Indiana University School of Medicine; Estados Unidos.
dc.description.fil Fil: Chhatwal, Jasmeer P. Harvard Medical School; Estados Unidos.
dc.description.fil Fil: Salloway, Stephen. Butler Hospital; Estados Unidos.
dc.description.fil Fil: Xiong, Chengjie. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Karch, Celeste M. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Cairns, Nigel. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Mori, Hiroshi. Osaka City University Medical School; Estados Unidos.
dc.description.fil Fil: Schofield, Peter R. Neuroscience Research Australia; Australia.
dc.description.fil Fil: Masters, Colin L. University of Melbourne; Australia.
dc.description.fil Fil: Goate, Alison M. Icahn School of Medicine at Mount Sinai; Estados Unidos.
dc.description.fil Fil: Buckles, Virginia. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Fox, Nick C. University College London; Reino Unido.
dc.description.fil Fil: Rossor, Martin. University College London; Reino Unido.
dc.description.fil Fil: Chrem Méndez, Patricio Alexis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina.
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina.
dc.description.fil Fil: Ringman, John M. Keck School of Medicine of University of Southern California; Estados Unidos.
dc.description.fil Fil: Höglinger, Günter. German Center for Neurodegenerative Disease; Alemania.
dc.description.fil Fil: Steiner, Harald. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Dieterich, Marianne. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Haass, Christian. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Laske, Christoph. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Morris, John C. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Bateman, Randall J. Washington University School of Medicine; Estados Unidos.
dc.description.fil Fil: Danek, Adrian. German Center for Neurodegenerative Diseases; Alemania.
dc.description.fil Fil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania.
dc.relation.ispartofVOLUME 142
dc.relation.ispartofNUMBER 5
dc.relation.ispartofPAGINATION 1429-1440
dc.relation.ispartofCOUNTRY Reino Unido
dc.relation.ispartofCITY Oxford
dc.relation.ispartofTITLE Brain
dc.relation.ispartofISSN 1460-2156
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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