Background/Aims: Few studies have examined predictors of reversion from mild cognitive impairment (MCI) to normal cognition. We sought to identify baseline predictors of reversion, using the National Alzheimer's Coordinating Center Uniform Data Set, by comparing MCI individuals who reverted to normal cognition to those who progressed to dementia. Methods: Participants (n = 1,208) meeting MCI criteria were evaluated at the baseline visit and 3 subsequent annual visits. Clusters of baseline predictors of MCI reversion included demographic/genetic data, global functioning, neuropsychological functioning, medical health/dementia risk score, and neuropsychiatric symptoms. Stepwise logistic regression models identified predictors of MCI reversion per cluster, which were then entered into a final comprehensive model to find overall predictor(s). Results: At 2 years, 175 (14%) reverted to normal cognition, 612 (51%) remained MCI, and 421 (35%) progressed to dementia, with sustained diagnoses at 3 years. Significant variables associated with MCI reversion were younger age, being unmarried, absence of APOE ε4 allele, lower CDR-SOB score, and higher memory/language test scores. Conclusion: A relatively sizable proportion of MCI individuals reverted to normal cognition, which is associated with multiple factors previously noted. Findings may enhance MCI prognostic accuracy and increase precision of early intervention studies of dementia.

1.
Ganguli M, Snitz BE, Saxton JA, Chang CC, Lee CW, Vander Bilt J, et al: Outcomes of mild cognitive impairment by definition: a population study. Arch Neurol 2011;68:761-776.
2.
Lopez OL, Becker JT, Chang YF, Sweet RA, DeKosky ST, Gach MH, et al: Incidence of mild cognitive impairment in the Pittsburgh Cardiovascular Health Study-Cognition Study. Neurology 2012;79:1599-1606.
3.
Mitchell AJ, Shiri-Feshki M: Rate of progression of mild cognitive impairment to dementia - meta-analysis of 41 robust inception cohort studies. Acta Psychiatr Scand 2009;119:252-265.
4.
Petersen RC: Clinical practice. Mild cognitive impairment. N Eng J Med 2011;364:2227-2234.
5.
Sachdev PS, Blacker D, Blazer DG, Ganguli M, Jeste DV, Paulsen JS, et al: Classifying neurocognitive disorders: the DSM-5 approach. Nat Rev Neurol 2014;10:634-642.
6.
Koepsell TD, Monsell SE: Reversion from mild cognitive impairment to normal or near-normal cognition: risk factors and prognosis. Neurology 2012;79:1591-1598.
7.
Ganguli M, Dodge HH, Shen C, DeKosky ST: Mild cognitive impairment, amnestic type: an epidemiologic study. Neurology 2004;63:115-121.
8.
Han JW, Kim TH, Lee SB, Park JH, Lee JJ, Huh Y, et al: Predictive validity and diagnostic stability of mild cognitive impairment subtypes. Alzheimers Dement 2012;8:553-559.
9.
Roberts RO, Knopman DS, Mielke MM, Cha RH, Pankratz VS, Christianson TJH, et al: Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal. Neurology 2014;82:317-325.
10.
Sachdev PS, Lipnicki DM, Crawford J, Reppermund S, Kochan NA, Trollor JN, et al: Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: a population-based study. PloS One 2013;8:e59649.
11.
Lezak MD, Howieson DB, Bigler ED, Tranel D: Neuropsychological Assessment, ed 5. New York, Oxford University Press, 2012.
12.
Park MH, Han C: Is there an MCI reversion to cognitively normal? Analysis of Alzheimer's disease biomarkers profiles. In Psychogeriatr 2015;27:429-437.
13.
Tokuchi R, Hishikawa N, Kurata T, Sato K, Kono S, Yamashita T, et al: Clinical and demographic predictors of mild cognitive impairment for converting to Alzheimer's disease and reverting to normal cognition. J Neurol Sci 2014;346:288-292.
14.
Pandya SY, Clem MA, Silva LM, Woon FL: Does mild cognitive impairment always lead to dementia? A review. J Neurol Sci 2016;369:57-62.
15.
Beekly DL, Ramos EM, Lee WW, Deitrich WD, Jacka ME, Wu J, et al: The National Alzheimer's Coordinating Center (NACC) database: the Uniform Data Set. Alzheimer Dis Assoc Disord 2007;21:249-258.
16.
Morris JC, Weintraub S, Chui HC, Cummings J, Decarli C, Ferris S, et al: The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer Dis Assoc Disord 2006;20:210-216.
17.
Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J: Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006;5:735-741.
18.
Exalto LG, Quesenberry CP, Barnes D, Kivipelto M, Biessels GJ, Whitmer RA: Midlife risk score for the prediction of dementia four decades later. Alzheimers Dement 2014;10:562-570.
19.
Petersen RC: Mild cognitive impairment as a diagnostic entity. J Int Med 2004;256:183-194.
20.
Weintraub S, Salmon D, Mercaldo N, Ferris S, Graff-Radford NR, Chui H, et al: The Alzheimer's Disease Centers' Uniform Data Set (UDS): the neuropsychological test battery. Alzheimer Dis Assoc Dis 2009;23:91.
21.
Shirk SD, Mitchell MB, Shaughnessy LW, Sherman JC, Locascio JJ, Weintraub S, et al: A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery. Alzheimers Res Ther 2011;3:32.
22.
Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, et al: Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci 2000;12:233-239.
23.
Jorm AF: History of depression as a risk factor for dementia: an updated review. Aust N Z J Psychiatry 2001;35:776-781.
24.
Somme J, Fernandez-Martinez M, Molano A, Zarranz JJ: Neuropsychiatric symptoms in amnestic mild cognitive impairment: increased risk and faster progression to dementia. Current Alzheimer Res 2013;10:86-94.
25.
Greiner M, Pfeiffer D, Smith RD: Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med 2000;45:23-41.
26.
Gomar JJ, Bobes-Bascaran MT, Conejero-Goldberg C, Davies P, Goldberg TE; Alzheimer's Disease Neuroimaging Initiative: Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative. Arch Gen Psychiatry 2011;68:961-969.
27.
Hakansson K, Rovio S, Helkala EL, Vilska AR, Winblad B, Soininen H, et al: Association between mid-life marital status and cognitive function in later life: population based cohort study. BMJ 2009;339:b2462.
28.
Steenland K, Macneil J, Bartell S, Lah J: Analyses of diagnostic patterns at 30 Alzheimer's disease centers in the US. Neuroepidemiology 2010;35:19-27.
29.
Loewenstein DA, Acevedo A, Small BJ, Agron J, Crocco E, Duara R: Stability of different subtypes of mild cognitive impairment among the elderly over a 2- to 3-year follow-up period. Dement Geriatr Cogn Disord 2009;27:418-423.
30.
Teng E, Tingus KD, Lu PH, Cummings JL: Persistence of neuropsychological testing deficits in mild cognitive impairment. Dement Geriatr Cogn Disord 2009;28:168-178.
31.
Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, et al: The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimers Dement 2012;8(suppl 1):S1-S68.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.