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      Diabetes mellitus and risk of dementia: A meta‐analysis of prospective observational studies

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          Abstract

          Aims/Introduction

          The aim of the present study was to investigate the association between diabetes and the risk of all type dementia ( ATD), Alzheimer's disease ( AD) and vascular dementia ( VaD).

          Materials and Methods

          Prospective observational studies describing the incidence of ATD, AD and VaD in patients with diabetes mellitus were extracted from PubMed, EMBASE and other databases up to January 2012. Pooled relative risk ( RR) estimates and 95% confidence intervals ( CIs) were calculated using the random‐effects model. Subgroup analyses and sensitivity analysis were also carried out.

          Results

          A total of 28 studies contributed to the analysis. Pooled RR of developing ATD ( n = 20) was 1.73 (1.65–1.82, I 2 = 71.2%), AD ( n = 20) was 1.56 (1.41–1.73, I 2 = 9.8%) and VaD ( n = 13) was 2.27 (1.94–2.66, I 2 = 0%) in patients with diabetes mellitus. Higher and medium quality studies did not show any significant difference for pooled RR for ATD, AD or VaD. Sensitivity analyses showed robustness of pooled RR among ATD, AD and VaD, showing no single study had a major impact on pooled RR.

          Conclusions

          The results showed a 73% increased risk of ATD, 56% increase of AD and 127% increase of VaD in diabetes patients.

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          Most cited references35

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          Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

          G C Román, T K Tatemichi, T Erkinjuntti … (1993)
          Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
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            Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders.

            Louis A Profenno, Anton P Porsteinsson, Stephen Faraone (2010)
            Late-onset Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder with major risk factors including advanced age, presence of an apolipoprotein E epsilon4 (APOE4) allele, and family history of AD. Other risk factors may be obesity and diabetes and related disorders, which are highly prevalent. We reviewed longitudinal epidemiological studies of body mass, diabetes, metabolic syndrome, and glucose and insulin levels on risk for AD. We conducted meta-analyses of the results from these studies. For obesity assessed by body mass index, the pooled effect size for AD was 1.59 (95% confidence interval [CI] 1.02-2.5; z = 2.0; p = .042), and for diabetes, the pooled effect size for AD was 1.54 (95% CI 1.33-1.79; z = 5.7; p < .001). Egger's test did not find significant evidence for publication bias in the meta-analysis for obesity (t = -1.4, p = .21) or for diabetes (t = -.86, p = .42). Since these disorders are highly comorbid, we conducted a meta-analysis combining all studies of obesity, diabetes, and abnormal glucose or insulin levels, which yielded a highly significant pooled effect size for AD of 1.63 (95% CI 1.39-1.92; z = 5.9; p < .001). Obesity and diabetes significantly and independently increase risk for AD. Though the level of risk is less than that with the APOE4 allele, the high prevalence of these disorders may result in substantial increases in future incidence of AD. Physiological changes common to obesity and diabetes plausibly promote AD. Published by Elsevier Inc.
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              Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study.

              S Ahtiluoto, T. Polvikoski, M Peltonen … (2010)
              To investigate the relation of diabetes to dementia, Alzheimer disease (AD), and vascular dementia (VaD), through analyses of incidence, mortality, and neuropathologic outcomes in a prospective population-based study of the oldest old. The Vantaa 85+ study included 553 residents living in the city of Vantaa, Finland, and aged ≥85 years on April 1, 1991. Survivors were reexamined in 1994, 1996, 1999, and 2001. Autopsies were performed in 291 persons who died during the follow-up (48% of total population). Diabetes was assessed according to self-report, medical record of physician-diagnosed diabetes, or use of antidiabetic medication. Macroscopic infarcts were identified from 1-cm coronal slices of cerebral hemispheres, 5-mm transverse brainstem slices, and sagittal cerebellum slices. Methenamine silver staining was used for β-amyloid, methenamine silver-Bodian staining for neurofibrillary tangles, and modified Bielschowsky method for neuritic plaques. Cox proportional hazards and multiple logistic regression models were used to analyze the association of diabetes with dementia and neuropathology, respectively. Diabetes at baseline doubled the incidence of dementia, AD, and VaD, and increased mortality. Individuals with diabetes were less likely to have β-amyloid (hazard ratio [HR] [95% confidence interval (CI)] was 0.48 [0.23-0.98]) and tangles (HR [95% CI] 0.72 [0.39-1.33]) but more likely to have cerebral infarcts (HR [95% CI] 1.88 [1.06-3.34]) after all adjustments. Elderly patients with diabetes develop more extensive vascular pathology, which alone or together with AD-type pathology (particularly in APOE ε4 carriers) results in increased dementia risk.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Diabetes Investig
                Journal ID (iso-abbrev): J Diabetes Investig
                Journal ID (doi): 10.1111/(ISSN)2040-1124
                Journal ID (publisher-id): JDI
                Title: Journal of Diabetes Investigation
                Publisher: Wiley-Blackwell
                ISSN (Print): 2040-1116
                ISSN (Electronic): 2040-1124
                Publication date (Electronic): 26 April 2013
                Publication date (Print): 27 November 2013
                Volume: 4
                Issue: 6 ( doiID: 10.1111/jdi.2013.4.issue-6 )
                Pages: 640-650
                Affiliations
                [ 1 ] Clinical Research Unit Department of Pharmacy PracticeNational Institute of Pharmaceutical Education and Research MohaliIndia
                [ 2 ] Clinical Pharmacology and TherapeuticsUniversity of Hertfordshire HertfordshireUK
                [ 3 ] Department of EndocrinologyPostgraduate Institute of Medical Education and Research ChandigarhIndia
                Author notes
                [*] [* ] Corresponding author. Dipika Bansal Tel.: +91‐869‐9494382 Fax: +91‐172‐2744401

                E‐mail address: dipikabansal079@ 123456gmail.com

                Article
                Publisher ID: JDI12087
                DOI: 10.1111/jdi.12087
                PMC ID: 4020261
                PubMed ID: 24843720
                SO-VID: 99d238ef-8966-4810-9f61-b59ffc9e5608
                Copyright © Copyright © 2013 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd© 2013 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd
                History
                Date received : 05 September 2012
                Date revision received : 16 January 2013
                Date accepted : 01 March 2013
                Page count
                Pages: 11
                Categories
                Subject: Original Article
                Subject: Articles
                Subject: Clinical Science and Care
                Custom metadata
                source-schema-version-number 2.0
                component-id jdi12087
                cover-date November 2013
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLM version:3.9.3 mode:remove_FC converted:04.02.2014

                Keywords: dementia,diabetes mellitus,meta‐analysis
                Data availability:
                Keywords: dementia, diabetes mellitus, meta‐analysis

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