Conversion and Reversion Rates in Japanese Older People With Mild Cognitive Impairment



      Approximately 25% of individuals who are diagnosed with amnestic mild cognitive impairment (aMCI) revert to normal cognition (NC) rather than progressing to Alzheimer disease (AD). However, the prevalence of progression and reversion among older people in Asia remains unclear.


      A prospective cohort study.


      A community in Japan.


      A total of 4153 individuals without dementia aged ≥65 years were classified as having NC, aMCI single domain (aMCIs), non-aMCI single domain (naMCIs), aMCI multiple domain (aMCIm), non-aMCI multiple domain (naMCIm), or global cognitive impairment (GCI).


      The National Center for Geriatrics and Gerontology-Functional Assessment Tool and the Mini-Mental State Examination were used to conduct cognitive screening. The participants completed baseline (August 2011 to June 2012) and follow-up (August 2015 to June 2016) assessments. We followed up monthly for newly incident AD, as recorded by the Japanese National Health Insurance and Later-Stage Medical Care systems. Multiple imputation was used to adjust for selection bias and loss of information.


      At 4-year follow-up, the reversion rates to NC in aMCIs, naMCIs, aMCIm, naMCIm, and GCI were 38.7%, 57.0%, 25.7%, 20.9%, and 43.7%, respectively. Of the participants with NC, aMCIs, naMCIs, aMCIm, naMCIm, and GCI at baseline, 4.7%, 4.5%, 13.1%, 20.6%, 21.6%, and 14.3%, respectively, were subsequently diagnosed with AD. We found significant associations between incident AD and naMCIs [hazard ratio (HR) compared to NC: 2.18, 95% confidence interval (CI): 1.45-3.26], and between AD and aMCIm (HR: 4.39, 95% CI: 2.06-9.39) and between AD and naMCIm (HR: 3.60, 95% CI: 2.13-6.08). However, the association between incident AD and aMCIs and between AD and GCI did not reach significance.


      Reversion to NC from MCI and GCI was frequent, and individuals with aMCIs and GCI did not show higher risk of incident AD than those with NC. Older adults with multiple cognitive impairments may be potential targets for preventing dementia.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the American Medical Directors Association
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Petersen R.C.
        • Smith G.E.
        • Waring S.C.
        • et al.
        Mild cognitive impairment: Clinical characterization and outcome.
        Arch Neurol. 1999; 56: 303-308
        • Jean L.
        • Bergeron M.E.
        • Thivierge S.
        • Simard M.
        Cognitive intervention programs for individuals with mild cognitive impairment: Systematic review of the literature.
        Am J Geriatr Psychiatry. 2010; 18: 281-296
        • Ward A.
        • Tardiff S.
        • Dye C.
        • Arrighi H.M.
        Rate of conversion from prodromal Alzheimer's disease to Alzheimer's dementia: A systematic review of the literature.
        Dement Geriatr Cogn Dis Extra. 2013; 3: 320-332
        • Mitchell A.J.
        • 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
        • Malek-Ahmadi M.
        Reversion from mild cognitive impairment to normal cognition: A meta-analysis.
        Alzheimer Dis Assoc Disord. 2016; 30: 324-330
        • Ismail Z.
        • Rajji T.K.
        • Shulman K.I.
        Brief cognitive screening instruments: An update.
        Int J Geriatr Psychiatry. 2010; 25: 111-120
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Creavin S.T.
        • Wisniewski S.
        • Noel-Storr A.H.
        • et al.
        Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations.
        Cochrane Database Syst Rev. 2016; : CD011145
        • Ganguli M.
        • Blacker D.
        • Blazer D.G.
        • et al.
        Classification of neurocognitive disorders in DSM-5: A work in progress.
        Am J Geriatr Psychiatry. 2011; 19: 205-210
        • Ganguli M.
        Can the DSM-5 framework enhance the diagnosis of MCI?.
        Neurology. 2013; 81: 2045-2050
        • O'Bryant S.E.
        • Humphreys J.D.
        • Smith G.E.
        • et al.
        Detecting dementia with the Mini-Mental State Examination in highly educated individuals.
        Arch Neurol. 2008; 65: 963-967
        • Shimada H.
        • Tsutsumimoto K.
        • Lee S.
        • et al.
        Driving continuity in cognitively impaired older drivers.
        Geriatr Gerontol Int. 2016; 16: 508-514
        • Koepsell T.D.
        • Monsell S.E.
        Reversion from mild cognitive impairment to normal or near-normal cognition: Risk factors and prognosis.
        Neurology. 2012; 79: 1591-1598
        • Egan M.F.
        • Kojima M.
        • Callicott J.H.
        • et al.
        The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.
        Cell. 2003; 112: 257-269
        • Makizako H.
        • Shimada H.
        • Park H.
        • et al.
        Evaluation of multidimensional neurocognitive function using a tablet personal computer: Test-retest reliability and validity in community-dwelling older adults.
        Geriatr Gerontol Int. 2013; 13: 860-866
        • Winblad B.
        • Palmer K.
        • Kivipelto M.
        • et al.
        Mild cognitive impairment—Beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment.
        J Intern Med. 2004; 256: 240-246
      1. Ministry of Health L, and Welfare of Japan. Annual health, labour, and welfare report 2011-2012. Available at: 2012. Accessed January 1, 2017.

        • Verghese J.
        • Lipton R.B.
        • Katz M.J.
        • et al.
        Leisure activities and the risk of dementia in the elderly.
        N Engl J Med. 2003; 348: 2508-2516
        • Morley J.E.
        • Morris J.C.
        • Berg-Weger M.
        • et al.
        Brain health: The importance of recognizing cognitive impairment: An IAGG consensus conference.
        J Am Med Dir Assoc. 2015; 16: 731-739
        • Yesavage J.A.
        Geriatric Depression Scale.
        Psychopharmacol Bull. 1988; 24: 709-711
        • Shimada H.
        • Makizako H.
        • Doi T.
        • et al.
        Combined prevalence of frailty and mild cognitive impairment in a population of elderly Japanese people.
        J Am Med Dir Assoc. 2013; 14: 518-524
        • Petersen R.C.
        • Stevens J.C.
        • Ganguli M.
        • et al.
        Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.
        Neurology. 2001; 56: 1133-1142
        • De Jager C.A.
        • Hogervorst E.
        • Combrinck M.
        • Budge M.M.
        Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.
        Psychol Med. 2003; 33: 1039-1050
        • Nestor P.J.
        • Scheltens P.
        • Hodges J.R.
        Advances in the early detection of Alzheimer's disease.
        Nat Med. 2004; 10: S34-S41
        • DeCarli C.
        • Mungas D.
        • Harvey D.
        • et al.
        Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia.
        Neurology. 2004; 63: 220-227
        • Hinrichs C.
        • Singh V.
        • Xu G.
        • Johnson S.C.
        Predictive markers for AD in a multi-modality framework: An analysis of MCI progression in the ADNI population.
        Neuroimage. 2011; 55: 574-589
        • Gibbons L.E.
        • Carle A.C.
        • Mackin R.S.
        • et al.
        A composite score for executive functioning, validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment.
        Brain Imaging Behav. 2012; 6: 517-527
        • Farias S.T.
        • Mungas D.
        • Reed B.R.
        • et al.
        Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts.
        Arch Neurol. 2009; 66: 1151-1157
        • Gao S.
        • Unverzagt F.W.
        • Hall K.S.
        • et al.
        Mild cognitive impairment, incidence, progression, and reversion: Findings from a community-based cohort of elderly African Americans.
        Am J Geriatr Psychiatry. 2014; 22: 670-681
        • Roberts R.O.
        • Knopman D.S.
        • Mielke M.M.
        • et al.
        Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal.
        Neurology. 2014; 82: 317-325
        • Brodaty H.
        • Heffernan M.
        • Kochan N.A.
        • et al.
        Mild cognitive impairment in a community sample: The Sydney Memory and Ageing Study.
        Alzheimers Dement. 2013; 9: 310-317.e1
        • Rapp S.R.
        • Legault C.
        • Henderson V.W.
        • et al.
        Subtypes of mild cognitive impairment in older postmenopausal women: The Women's Health Initiative Memory Study.
        Alzheimer Dis Assoc Disord. 2010; 24: 248-255
        • Mufson E.J.
        • Binder L.
        • Counts S.E.
        • et al.
        Mild cognitive impairment: Pathology and mechanisms.
        Acta Neuropathol. 2012; 123: 13-30
        • Mungas D.
        In-office mental status testing: A practical guide.
        Geriatrics. 1991; 46 (63, 66): 54-58
        • Grut M.
        • Fratiglioni L.
        • Viitanen M.
        • Winblad B.
        Accuracy of the Mini-Mental Status Examination as a screening test for dementia in a Swedish elderly population.
        Acta Neurol Scand. 1993; 87: 312-317
        • Sachdev P.S.
        • Lipnicki D.M.
        • Crawford J.
        • et al.
        Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: A population-based study.
        PLoS One. 2013; 8: e59649
        • Cruz-Oliver D.M.
        • Malmstrom T.K.
        • Roegner M.
        • et al.
        Cognitive deficit reversal as shown by changes in the Veterans Affairs Saint Louis University Mental Status (SLUMS) examination scores 7.5 years later.
        J Am Med Dir Assoc. 2014; 15: 687.e5-687.e10
        • Okura Y.
        • Urban L.H.
        • Mahoney D.W.
        • et al.
        Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure.
        J Clin Epidemiol. 2004; 57: 1096-1103