Mid- and Late-life Diabetes in Relation to the Risk of Dementia: A Population-based Twin Study
Weili Xu; Chengxuan Qiu; Margaret Gatz; Nancy L. Pedersen; Boo Johansson; Laura Fratiglioni
Weili Xu; Chengxuan Qiu; Margaret Gatz; Nancy L. Pedersen; Boo Johansson; Laura Fratiglioni
Abstract
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 65 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.
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 65 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 65 years), the risk effect of mid-life diabetes (onset age < 65 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 diabetesdementia association but could not account for the mid-life diabetes-dementia association.
Introduction
Population-based longitudinal studies have shown that the risk of dementia in general is increased in people with diabetes. Even pre-diabetes has been associated with an increased risk of dementia and Alzheimer disease. Although diabetes may be linked to dementia through several biologically plausible pathways, our understanding of the mechanisms for such an association is still limited. Both dementia and diabetes are complex age- and lifestyle-related disorders. In addition to strong influence of environmental elements, genetic components also play a part in both Alzheimer's disease and diabetes.
Epidemiological and clinical studies have reported that environmental factors acting in early life, such as birth weight and childhood socioeconomic situation, are also involved in the development of diabetes as well as dementia. Evidence from genetic and epidemiological studies has indicated that genetic and environmental factors may interact to affect the association between diabetes and dementia during the life course. The recent upsurge of interest in applying a life-course approach to chronic disease epidemiology and the hypothesis of "developmental origins of adult disease" prompt renewed attention to twin studies.
Twins provide naturally matched pairs, in which confounding effects of a large number of potentially causal factors (e.g., genetics and childhood environment) may be removed when comparisons are made between twins. Because twins are generally reared together, they share their early-life environment. Twin studies involving a life-course approach may help to identify genetic influences and timing of environmental influences on the relationship between age-related disorders. In the current study, we sought to 1) verify the association between diabetes and risk of dementia and its main subtypes in twins, 2) examine whether the effect of diabetes on dementia risk varies according to age of diabetes onset, and 3) explore whether genetic and early-life familial environmental factors could explain this association using data from the population-based Swedish twin cohort.
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Introduction
Population-based longitudinal studies have shown that the risk of dementia in general is increased in people with diabetes. Even pre-diabetes has been associated with an increased risk of dementia and Alzheimer disease. Although diabetes may be linked to dementia through several biologically plausible pathways, our understanding of the mechanisms for such an association is still limited. Both dementia and diabetes are complex age- and lifestyle-related disorders. In addition to strong influence of environmental elements, genetic components also play a part in both Alzheimer's disease and diabetes.
Epidemiological and clinical studies have reported that environmental factors acting in early life, such as birth weight and childhood socioeconomic situation, are also involved in the development of diabetes as well as dementia. Evidence from genetic and epidemiological studies has indicated that genetic and environmental factors may interact to affect the association between diabetes and dementia during the life course. The recent upsurge of interest in applying a life-course approach to chronic disease epidemiology and the hypothesis of "developmental origins of adult disease" prompt renewed attention to twin studies.
Twins provide naturally matched pairs, in which confounding effects of a large number of potentially causal factors (e.g., genetics and childhood environment) may be removed when comparisons are made between twins. Because twins are generally reared together, they share their early-life environment. Twin studies involving a life-course approach may help to identify genetic influences and timing of environmental influences on the relationship between age-related disorders. In the current study, we sought to 1) verify the association between diabetes and risk of dementia and its main subtypes in twins, 2) examine whether the effect of diabetes on dementia risk varies according to age of diabetes onset, and 3) explore whether genetic and early-life familial environmental factors could explain this association using data from the population-based Swedish twin cohort.
DOWNLOAD PDF COMPLETE HERE
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