Randomized controlled trials in mild cognitive impairment: Sources of variability

Ronald Carl Petersen, Ronald G. Thomas, Paul S. Aisen, Richard C. Mohs, Maria C. Carrillo, Marilyn S. Albert

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating-sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings.

Original languageEnglish (US)
Pages (from-to)1751-1758
Number of pages8
JournalNeurology
Volume88
Issue number18
DOIs
StatePublished - May 2 2017

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Alzheimer Disease
Randomized Controlled Trials
National Institute on Aging (U.S.)
Placebos
Rivastigmine
Neuroimaging
Industry
Clinical Trials
Galantamine
Dementia
Outcome Assessment (Health Care)
Cognitive Dysfunction
Population

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Petersen, R. C., Thomas, R. G., Aisen, P. S., Mohs, R. C., Carrillo, M. C., & Albert, M. S. (2017). Randomized controlled trials in mild cognitive impairment: Sources of variability. Neurology, 88(18), 1751-1758. https://doi.org/10.1212/WNL.0000000000003907

Randomized controlled trials in mild cognitive impairment : Sources of variability. / Petersen, Ronald Carl; Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

In: Neurology, Vol. 88, No. 18, 02.05.2017, p. 1751-1758.

Research output: Contribution to journalArticle

Petersen, RC, Thomas, RG, Aisen, PS, Mohs, RC, Carrillo, MC & Albert, MS 2017, 'Randomized controlled trials in mild cognitive impairment: Sources of variability', Neurology, vol. 88, no. 18, pp. 1751-1758. https://doi.org/10.1212/WNL.0000000000003907
Petersen, Ronald Carl ; Thomas, Ronald G. ; Aisen, Paul S. ; Mohs, Richard C. ; Carrillo, Maria C. ; Albert, Marilyn S. / Randomized controlled trials in mild cognitive impairment : Sources of variability. In: Neurology. 2017 ; Vol. 88, No. 18. pp. 1751-1758.
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