Molecular connexions between dementia and diabetes

Cole, Adam R.; Astell, Arlene; Green, Charlotte; Sutherland, Calum

doi:10.1016/j.neubiorev.2007.04.004

Cited by 144 publications

(120 citation statements)

References 232 publications

(219 reference statements)

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“…These findings suggest that the association observed in the unmatched case-control analysis between late-life diabetes and dementia is more likely to be endogenous. Our findings support recent evidence that the molecular defects associated with the development of diabetes also contribute to an increased risk of all types of dementia (39). Genome-wide association studies have shown that the insulin-degrading enzyme (IDE) gene links to both late-onset Alzheimer's disease and type 2 diabetes (40).…”

Section: Discussionsupporting

confidence: 90%

Mid- and Late-Life Diabetes in Relation to the Risk of Dementia

et al. 2009

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OBJECTIVE-We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association.RESEARCH DESIGN AND METHODS-This study included 13,693 twin individuals aged Ն65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self-or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression.RESULTS-Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51-2.38) for dementia, 1.69 (1.16 -2.36) for Alzheimer's disease, and 2.17 (1.36 -3.47) for vascular dementia. Compared with late-life diabetes (onset age Ն65 years), the risk effect of mid-life diabetes (onset age Ͻ65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05-5.51) and 0.68 (0.30 -1.53) for dementia related to mid-and late-life diabetes, respectively. CONCLUSIONS-Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes-dementia association but could not account for the mid-life diabetesdementia association. Diabetes 58:71-77, 2009

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Section: Discussionsupporting

confidence: 90%

Mid- and Late-Life Diabetes in Relation to the Risk of Dementia

et al. 2009

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“…These findings are consistent with one or more unmeasured diabetes-related factors being involved in the pathogenesis of AD in diabetes over and above CVD and its risk factors. Variables likely to be related to diabetes duration that have been considered possible causes of AD include chronic low-level inflammation, which is associated with atherosclerosis in type 2 diabetes [31], advanced glycation end-products [11], and hyperinsulinaemia and/or insulin resistance [10,12].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiovascular risk factors and atherosclerosis are also associated with dementia and AD [5][6][7] and the combination of diabetes and hypertension confers a high risk of dementia [8,9]. In addition, non-vascular mechanisms may also contribute to dementia in diabetes [10], including excess formation of advanced glycation endproducts [11] and/or disturbed neuronal insulin signalling that may promote cerebral amyloidosis [12].…”

Section: Introductionmentioning

confidence: 99%

Predictors of cognitive impairment and dementia in older people with diabetes

et al. 2007

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Aims/hypothesis Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. Methods Survivors, aged ≥70 or more, were recruited from an existing observational cohort study 7.6±1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. Results Of 302 participants, aged 75.7±4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. Conclusions/interpretation Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

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“…Type 2 diabetes currently affects 250 million people worldwide [1], and about 300 million people with borderline diabetes are at increased risk of type 2 diabetes [2]. The global prevalent dementia cases are approximately 29 million, with 4.6 million new cases every year [3].…”

Section: Introductionmentioning

confidence: 99%

Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study

et al. 2009

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Aims/hypothesis Diabetes has been related to Alzheimer's disease with inconsistent findings. We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration. Methods A dementia-free cohort (n=1,248) aged ≥75 years was longitudinally examined to detect dementia, Alzheimer's disease and vascular dementia (VaD) cases (Diagnostic and

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Molecular connexions between dementia and diabetes

Cited by 144 publications

References 232 publications

Mid- and Late-Life Diabetes in Relation to the Risk of Dementia

Mid- and Late-Life Diabetes in Relation to the Risk of Dementia

Predictors of cognitive impairment and dementia in older people with diabetes

Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study

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