Cognitive and functional changes associated with Aβ pathology and the progression to mild cognitive impairment

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Insel, Philip S.Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups (författare)

Cognitive and functional changes associated with Aβ pathology and the progression to mild cognitive impairment

Artikel/kapitelEngelska2016

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Elsevier BV,2016
10 s.

Nummerbeteckningar

LIBRIS-ID:oai:lup.lub.lu.se:99f1e2f1-340d-4f58-9eac-8f36b9a80e5b
https://lup.lub.lu.se/record/99f1e2f1-340d-4f58-9eac-8f36b9a80e5bURI
https://doi.org/10.1016/j.neurobiolaging.2016.08.017DOI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:art swepub-publicationtype
Ämneskategori:ref swepub-contenttype

Anmärkningar

Cognitively-normal people with evidence of β-amyloid (Aβ) pathology and subtle cognitive dysfunction are believed to be at high risk for progression to mild cognitive impairment due to Alzheimer's disease (AD). Clinical trials in later stages of AD typically include a coprimary endpoint to demonstrate efficacy on both cognitive and functional assessments. Recent trials focus on cognitively-normal people, but functional decline has not been explored for trial designs in this group. The goal of this study was therefore to characterize cognitive and functional decline in (1) cognitively-normal people converting to mild cognitive impairment (MCI) and (2) cognitively-normal β-amyloid-positive (Aβ+) people. Specifically, we sought to identify and compare the cognitive and functional assessments and their weighted combinations that maximize the longitudinal decline specific to these 2 groups. We studied 68 people who converted from normal cognition to MCI and 70 nonconverters, as well as 137 Aβ+ and 210 β-amyloid-negative cognitively-normal people. We used bootstrap aggregation and cross-validated mixed-models to estimate the distribution of weights applied to cognitive and functional outcomes to form composites. We also evaluated best subset optimization. Using optimized composites, we estimated statistical power for a variety of clinical trial scenarios. Overall, 55.4% of cognitively-normal to MCI converters were Aβ+. Large gains in power estimates were obtained when requiring participants to have both subtle cognitive dysfunction and Aβ pathology compared with requiring Aβ pathology alone. Additional power resulted when including functional as well as cognitive outcomes as part of the composite. Composites formed by applying equal weights to all measures provided the highest estimates of cross-validated power, although similar to both continuous weight optimization and best subset optimization. Using a composite to detect a 30% slowing of decline, 80% power was obtained for predicted Aβ+ converters with 375 completers/arm for a 30-month trial using a combination of cognitive/ functional measures. In the Aβ+ group, power to approach levels suitable for a phase III clinical trial would require considerably larger sample sizes. Composites incorporating both cognitive and functional measures may substantially increase the power of a trial in a preclinical (Aβ+) AD population with subtle evidence of cognitive dysfunction.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Annan medicin och hälsovetenskap Gerontologi, medicinsk/hälsovetenskaplig inriktning hsv//swe
MEDICAL AND HEALTH SCIENCES Other Medical and Health Sciences Gerontology, specialising in Medical and Health Sciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
Clinical trials
Cognition
Composite
Function
Mild cognitive impairment
β-amyloid

Biuppslag (personer, institutioner, konferenser, titlar ...)

Donohue, Michael C.University of Southern California (författare)
Mackin, R. ScottUniversity of Southern California (författare)
Aisen, Paul S.University of Southern California (författare)
Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (författare)
Weiner, Michael W.University of California System (författare)
Mattsson, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-nmn (författare)
Klinisk minnesforskningForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

Ingår i:Neurobiology of Aging: Elsevier BV48, s. 172-1810197-4580

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Av författaren/redakt...: Insel, Philip S.; Donohue, Michael ...; Mackin, R. Scott; Aisen, Paul S.; Hansson, Oskar; Weiner, Michael ...; visa fler...; Mattsson, Niklas; visa färre...

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Av lärosätet: Lunds universitet

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