Original Study| Volume 22, ISSUE 9, P1912-1918.e2, September 2021

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Diabetes and Prediabetes Inhibit Reversion from Mild Cognitive Impairment to Normal Cognition



      Diabetes and prediabetes contribute to an increased risk of cognitive decline and dementia. Currently, it remains unclear whether elevated blood HbA1c levels, including prediabetes levels, affect reversion from mild cognitive impairment (MCI) to normal cognition. This study, therefore, aimed to examine the prospective associations of diabetes and prediabetes with reversion from MCI to normal cognition among community-dwelling older adults.


      Longitudinal cohort study with a 4-year follow-up.

      Setting and Participants

      Community-dwelling older adults with MCI, aged ≥65 years at baseline (n = 787).


      Participants’ medical history of diabetes and blood HbA1c levels at baseline were assessed, and they were classified as control, prediabetes, and diabetes. Objective cognitive screening was performed using a multicomponent neurocognitive test at baseline and follow-up. Reversion from MCI to normal cognition over 4 years was determined. In the longitudinal analysis, we performed multiple imputations to adjust for a selection bias and loss of information.


      The reversion rates of MCI in the control, prediabetes, and diabetes groups were 63.4%, 55.6%, and 42.9%, respectively, in the completed follow-up dataset, and 54.6%, 47.2%, and 34.1%, respectively, in the imputed dataset. Multivariate logistic regression showed that diabetes decreases the probability of MCI reversion both before and after multiple imputations [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.18–0.74 for before imputation, OR 0.37; 95% CI 0.19–0.72 for after imputation]. Furthermore, prediabetes also showed significantly decreased probabilities of MCI reversion both before and after multiple imputations (OR 0.57; 95% CI 0.34–0.94 for before imputation, OR 0.60; 95% CI 0.37–0.97 for after imputation).

      Conclusions and Implications

      Diabetes and prediabetes could inhibit MCI reversion. Adequate glycemic control may be effective in enhancing the reversion from MCI to normal cognition in a community setting.


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      1. Diabetes in America. 2018 (Available at:)
        • Tabák A.G.
        • Herder C.
        • Rathmann W.
        • et al.
        Prediabetes: A high-risk state for diabetes development.
        Lancet. 2012; 379: 2279-2290
        • American Diabetes Association
        2. Classification and diagnosis of diabetes: Standards of medical care in diabetes—2020.
        Diabetes Care. 2020; 43: S14-S31
        • Li G.
        • Han L.
        • Wang Y.
        • et al.
        Evaluation of ADA HbA1c criteria in the diagnosis of pre-diabetes and diabetes in a population of Chinese adolescents and young adults at high risk for diabetes: A cross-sectional study.
        BMJ Open. 2018; 8: e020665
        • Selvin E.
        • Crainiceanu C.M.
        • Brancati F.L.
        • Coresh J.
        Short-term variability in measures of glycemia and implications for the classification of diabetes.
        Arch Intern Med. 2007; 167: 1545-1551
        • Petersen R.C.
        • Smith G.E.
        • Waring S.C.
        • et al.
        Mild cognitive impairment: Clinical characterization and outcome.
        Arch Neurol. 1999; 56: 303-308
        • Petersen R.C.
        Mild cognitive impairment.
        N Engl J Med. 2011; 364: 2227-2234
        • 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
        • Shimada H.
        • Makizako H.
        • Doi T.
        • et al.
        Conversion and reversion rates in Japanese older people with mild cognitive impairment.
        J Am Med Dir Assoc. 2017; 18: 808.e1-808.e6
        • Malek-Ahmadi M.
        Reversion from mild cognitive impairment to normal cognition: A meta-analysis.
        Alzheimer Diş Assoc Disord. 2016; 30: 324-330
        • Biessels G.J.
        • Staekenborg S.
        • Brunner E.
        • et al.
        Risk of dementia in diabetes mellitus: A systematic review.
        Lancet Neurol. 2006; 5: 64-74
        • Ninomiya T.
        Diabetes mellitus and dementia.
        Curr Diab Rep. 2014; 14: 487
        • Gudala K.
        • Bansal D.
        • Schifano F.
        • Bhansali A.
        Diabetes mellitus and risk of dementia: A meta-analysis of prospective observational studies.
        J Diabetes Investig. 2013; 4: 640-650
        • Zheng F.
        • Yan L.
        • Yang Z.
        • et al.
        HbA1c, diabetes and cognitive decline: The English Longitudinal Study of Ageing.
        Diabetologia. 2018; 61: 839-848
        • Otsuka R.
        • Nishita Y.
        • Tange C.
        • et al.
        Hemoglobin A1c and 10-year information processing speed in Japanese community dwellers.
        Environ Health Prev Med. 2019; 24: 24
        • Dong S.
        • Dongwei L.
        • Zhang J.
        • et al.
        Individuals in the prediabetes stage exhibit reduced hippocampal tail volume and executive dysfunction.
        Brain Behav. 2019; 9: e01351
        • Crane P.K.
        • Walker R.
        • Hubbard R.A.
        • et al.
        Glucose levels and risk of dementia.
        N Engl J Med. 2013; 369: 540-548
        • Rawlings A.M.
        • Sharrett A.R.
        • Albert M.S.
        • et al.
        The association of late-life diabetes status and hyperglycemia with incident mild cognitive impairment and dementia: The ARIC study.
        Diabetes Care. 2019; 42: 1248-1254
        • van Buuren S.
        Multiple imputation of discrete and continuous data by fully conditional specification.
        Stat Methods Med Res. 2007; 16: 219-242
        • Qi L.
        • Wang Y.F.
        • Chen R.
        • et al.
        Strategies for imputing missing covariates in accelerated failure time models.
        Stat Med. 2018; 37: 3417-3436
        • Kashiwagi A.
        • Kasuga M.
        • Araki E.
        • et al.
        International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values.
        J Diabetes Investig. 2012; 3: 39-40
        • 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
        • 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
        • Makino K.
        • Lee S.
        • Bae S.
        • et al.
        Relationship between instrumental activities of daily living performance and incidence of mild cognitive impairment among older adults: A 48-month follow-up study.
        Arch Gerontol Geriatr. 2020; 88: 104034
        • 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
        • Ezzati A.
        • Katz M.J.
        • Derby C.A.
        • et al.
        Depressive symptoms predict incident dementia in a community sample of older adults: results from the Einstein Aging Study.
        J Geriatr Psychiatr Neurol. 2019; 32: 97-103
        • Doi T.
        • Shimada H.
        • Makizako H.
        • et al.
        Mild cognitive impairment, slow gait, and risk of disability: A prospective study.
        J Am Med Dir Assoc. 2015; 16: 1082-1086
        • Yaffe K.
        • Blackwell T.
        • Whitmer R.A.
        • et al.
        Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women.
        J Nutr Health Aging. 2006; 10: 293-295
        • 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
        • Gao Q.
        • Gwee X.
        • Feng L.
        • et al.
        Mild cognitive impairment reversion and progression: Rates and predictors in community-living older persons in the Singapore longitudinal ageing studies cohort.
        Dement Geriatr Cogn Disord Extra. 2018; 8: 226-237
        • Lee A.K.
        • Rawlings A.M.
        • Lee C.J.
        • et al.
        Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) cohort study.
        Diabetologia. 2018; 61: 1956-1965
        • Chatterjee S.
        • Peters S.A.
        • Woodward M.
        • et al.
        Type 2 diabetes as a risk factor for dementia in women compared with men: A pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia.
        Diabetes Care. 2016; 39: 300-307
        • Zhou J.B.
        • Tang X.Y.
        • Han Y.P.
        • et al.
        Prediabetes and structural brain abnormalities: Evidence from observational studies.
        Diabetes Metab Res Rev. 2020; 36: e3261
        • Luchsinger J.A.
        • Palta P.
        • Rippon B.
        • et al.
        Pre-diabetes, but not type 2 diabetes, is related to brain amyloid in late middle-age.
        J Alzheimers Dis. 2020; 75: 1241-1252
        • Xu W.
        • Caracciolo B.
        • Wang H.X.
        • et al.
        Accelerated progression from mild cognitive impairment to dementia in people with diabetes.
        Diabetes. 2010; 59: 2928-2935
        • Ganguli M.
        • Snitz B.E.
        • Saxton J.A.
        • et al.
        Outcomes of mild cognitive impairment by definition: A population study.
        Arch Neurol. 2011; 68: 761-767
        • Pandya S.Y.
        • Lacritz L.H.
        • Weiner M.F.
        • et al.
        Predictors of reversion from mild cognitive impairment to normal cognition.
        Dement Geriatr Cogn Disord. 2017; 43: 204-214
        • 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
        • Han J.W.
        • Kim T.H.
        • Lee S.B.
        • et al.
        Predictive validity and diagnostic stability of mild cognitive impairment subtypes.
        Alzheimers Dement. 2012; 8: 553-559
        • Verghese J.
        • Annweiler C.
        • Ayers E.
        • et al.
        Motoric cognitive risk syndrome: Multicountry prevalence and dementia risk.
        Neurology. 2014; 83: 718-726
        • Knopman D.S.
        • Gottesman R.F.
        • Sharrett A.R.
        • et al.
        Midlife vascular risk factors and midlife cognitive status in relation to prevalence of mild cognitive impairment and dementia in later life: The Atherosclerosis Risk in Communities Study.
        Alzheimers Dement. 2018; 14: 1406-1415
        • Trevisan C.
        • Limongi F.
        • Siviero P.
        • et al.
        Mild polypharmacy and MCI progression in older adults: The mediation effect of drug-drug interactions.
        Aging Clin Exp Res. 2021; 33: 49-56

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