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September 26, 2012
Letter to the Editor

Reversion from mild cognitive impairment to normal or near-normal cognition
Risk factors and prognosis

October 9, 2012 issue
79 (15) 1591-1598

Abstract

Objectives:

We sought to identify characteristics of individuals with mild cognitive impairment (MCI) that are associated with a relatively high probability of reverting back to normal cognition, and to estimate the risk of future cognitive decline among those who revert.

Methods:

We first studied 3,020 individuals diagnosed with MCI on at least 1 visit to an Alzheimer's Disease Center in the United States. All underwent standardized Uniform Data Set evaluations at their first visit with an MCI diagnosis and on a subsequent visit, about 1 year later, at which cognitive status was reassessed. Multiple logistic regression was used to identify predictors of reverting from MCI back to normal cognition. We then estimated the risk of developing MCI or dementia over the next 3 years among those who had reverted, compared with individuals who had not had a study visit with MCI.

Results:

About 16% of subjects diagnosed with MCI reverted back to normal or near-normal cognition approximately 1 year later. Five characteristics assessed at the first MCI visit contributed significantly to a model predicting a return to normal cognition: Mini-Mental State Examination (MMSE) score, Clinical Dementia Rating (CDR) score, MCI type, Functional Activities Questionnaire (FAQ) score, and APOE ϵ4 status. Survival analysis showed that the risk of retransitioning to MCI or dementia over the next 3 years was sharply elevated among those who had MCI and then improved, compared with individuals with no history of MCI.

Conclusions:

Even in a cohort of patients seen at dementia research centers, reversion from MCI was fairly common. Nonetheless, those who reverted remained at increased risk for future cognitive decline.

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Supplementary Material

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Letters to the Editor
24 October 2012
Reversion from mild cognitive impairment or regression to the mean?
Gilad Rosenberg, Vice President, Clinical Development

Koepsell and Monsell analyzed a population of subjects with mild cognitive impairment (MCI) who allegedly reverted back to normal cognition, only to remain at a high risk of subsequently progressing to Alzheimer disease. [1] Out of 3,020 subjects diagnosed with MCI at their initial study visit, Koepsell and Monsell's analysis focused on a subgroup of 483 subjects who--one year later--had no MCI.

Regression to the mean (RTM) is a statistical phenomenon that can make natural variation in repeated data look like real change. [2] Isn't it possible that the observed reversion from MCI was in fact regression to the mean?

1. Koepsell TD, Monsell SE. Reversion from mild cognitive impairment to normal or near-normal cognition: Risk factors and prognosis. Neurology 2012; 79:1591-1598.

2. Barnett A G, van der Pols JC, Dobson AJ. Regression to the mean: What it is and how to deal with it. International Journal of Epidemiology 2005; 34: 215- 220.

For disclosures, contact editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 79Number 15October 9, 2012
Pages: 1591-1598
PubMed: 23019264

Publication History

Received: March 2, 2012
Accepted: May 23, 2012
Published online: September 26, 2012
Published in print: October 9, 2012

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Disclosure

T.D. Koepsell reports no disclosures. S.E. Monsell receives research support from the NIH. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

Thomas D. Koepsell, MD, MPH
From the Departments of Epidemiology and Health Services (T.D.K.) and the National Alzheimer's Coordinating Center and Department of Epidemiology (S.E.M.), University of Washington, Seattle.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
Epidemiologic Methods: Studying the Occurrence of Illness. New York: Oxford University Press, 2003. Injury Control: A Guide to Research and Evaluation. New York: Cambridge University Press, 2001.
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
JAMA, Statistical/methodological reviewer of manuscripts
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
U.S. Department of Veterans Affairs, Seattle Epidemiologic Research and Information Center (no grant number). Associate Director, 1997-2011. National Institutes of Health, Grant No. U01 AG016976. Associate Director, 2004-2011. Centers for Disease Control and Prevention, Grant No. R49 CE 001021. Co-Investigator, 2006-2011.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sarah E. Monsell, MS
From the Departments of Epidemiology and Health Services (T.D.K.) and the National Alzheimer's Coordinating Center and Department of Epidemiology (S.E.M.), University of Washington, Seattle.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
My salary is paid by NIA cooperative agreement UO1 AG016976
Consultancies:
1.
A member of my immediate family was a paid consultant for Novartis Pharmacy AG through January 2011 for an anti-malaria drug
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
My salary is paid by NIA cooperative agreement UO1 AG016976
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Study funding: NIA grant UO1 AG016976.
Correspondence & reprint requests to Ms. Monsell: [email protected]

Author Contributions

T.D. Koepsell contributed to study concept and design and interpretation of data, performed statistical analysis, and edited the manuscript for content. S.E. Monsell contributed to the study concept and design, interpretation of data, and drafting the manuscript.

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