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Determining clinica...
Determining clinically meaningful decline in preclinical Alzheimer disease
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- Insel, Philip S. (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,University of California, San Francisco
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- Weiner, Michael (author)
- University of California, San Francisco,San Francisco Veterans Administration Medical Center
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- Mackin, R. Scott (author)
- University of California, San Francisco,San Francisco Veterans Administration Medical Center
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- Mormino, Elizabeth (author)
- Stanford University
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- Lim, Yen Ying (author)
- University of Melbourne
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- Stomrud, Erik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Palmqvist, Sebastian (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Masters, Colin L. (author)
- University of Melbourne
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- Maruff, Paul T. (author)
- University of Melbourne
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Mattsson, Niklas (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,Clinical Memory Research,Lund University Research Groups
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(creator_code:org_t)
- 2019
- 2019
- English.
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In: Neurology. - 1526-632X. ; 93:4, s. 322-333
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Abstract
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- OBJECTIVE: To determine the time required for a preclinical Alzheimer disease population to decline in a meaningful way, use estimates of decline to update previous clinical trial design assumptions, and identify factors that modify β-amyloid (Aβ)-related decline. METHODS: In 1,120 cognitively unimpaired individuals from 3 international cohorts, we estimated the relationship between Aβ status and longitudinal changes across multiple cognitive domains and assessed interactions between Aβ and baseline factors. Power analyses were performed to explore sample size as a function of treatment effect. RESULTS: Cognitively unimpaired Aβ+ participants approach mild cognitive impairment (MCI) levels of performance 6 years after baseline, on average. Achieving 80% power in a simulated 4-year treatment trial, assuming a 25% treatment effect, required 2,000 participants/group. Multiple factors interacted with Aβ to predict cognitive decline; however, these findings were all cohort-specific. Despite design differences across the cohorts, with large sample sizes and sufficient follow-up time, the Aβ+ groups declined consistently on cognitive composite measures. CONCLUSIONS: A preclinical AD population declines to the cognitive performance of an early MCI population in 6 years. Slowing this rate of decline by 40%-50% delays clinically relevant impairment by 3 years-a potentially meaningful treatment effect. However, assuming a 40%-50% drug effect highlights the difficulties in preclinical AD trial design, as a more commonly assumed treatment effect of 25% results in a required sample size of 2,000/group. Designers of preclinical AD treatment trials need to prepare for larger and longer trials than are currently being considered. Interactions with Aβ status were inconsistent and not readily generalizable.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- art (subject category)
- ref (subject category)
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Neurology
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- By the author/editor
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Insel, Philip S.
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Weiner, Michael
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Mackin, R. Scott
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Mormino, Elizabe ...
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Lim, Yen Ying
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Stomrud, Erik
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show more...
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Palmqvist, Sebas ...
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Masters, Colin L ...
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Maruff, Paul T.
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Hansson, Oskar
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Mattsson, Niklas
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Neurology
- By the university
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Lund University