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Biomarkers and cogn...
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Insel, P. S.
(författare)
Biomarkers and cognitive endpoints to optimize trials in Alzheimer's disease
- Artikel/kapitelEngelska2015
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LIBRIS-ID:oai:gup.ub.gu.se/277026
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https://gup.ub.gu.se/publication/277026URI
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https://doi.org/10.1002/acn3.192DOI
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Ämneskategori:art swepub-publicationtype
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Objective: To find the combination of candidate biomarkers and cognitive endpoints to maximize statistical power and minimize cost of clinical trials of healthy elders at risk for cognitive decline due to Alzheimer's disease. Methods: Four-hundred and twelve cognitively normal participants were followed over 7 years. Nonlinear methods were used to estimate the longitudinal trajectories of several cognitive outcomes including delayed memory recall, executive function, processing speed, and several cognitive composites by subgroups selected on the basis of biomarkers, including APOE-epsilon 4 allele carriers, cerebrospinal fluid biomarkers (A beta(42), total tau, and phosphorylated tau), and those with small hippocampi. Results: Derived cognitive composites combining Alzheimer's Disease Assessment Scale (ADAS)-cog scores with additional delayed memory recall and executive function components captured decline more robustly across biomarker groups than any measure of a single cognitive domain or ADAS-cog alone. Substantial increases in power resulted when including only participants positive for three or more biomarkers in simulations of clinical trials. Interpretation: Clinical trial power may be improved by selecting participants on the basis of amyloid and neurodegeneration biomarkers and carefully tailoring primary cognitive endpoints to reflect the expected decline specific to these individuals.
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Mattsson, Niklas,1979Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xmattn
(författare)
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Mackin, R. S.
(författare)
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Kornak, J.
(författare)
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Nosheny, R.
(författare)
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Tosun-Turgut, D.
(författare)
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Donohue, M. C.
(författare)
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Aisen, P. S.
(författare)
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Weiner, M. W.
(författare)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Annals of Clinical and Translational Neurology: Wiley2:5, s. 534-5472328-9503
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