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

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 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

Cardiovascular risk in cognitively preserved elderlies is associated with glucose hypometabolism in the posterior cingulate cortex and precuneus regardless of brain atrophy and apolipoprotein gene variations

“…Such conditions are nowadays recognized as risk factors not only for vascular dementia but also for AD (Launer et al 2000;Meyer et al 2000;Knopman et al 2001;Stuerenburg et al 2005;Rosendorff et al 2007;Irie et al 2008;Xu et al 2009). There are also findings from post mortem and in vivo morphometric magnetic resonance imaging (MRI) studies indicating that brain lesions of vascular origin, such as white matter hyperintensities, stroke, and lacunar infarcts, may be significantly associated with AD (Craft 2009;Erkinjuntti and Gauthier 2009;Teipel et al 2009).…”

Association of duration of type 2 diabetes with short term and working memory

“…16,17 Severe diabetes mellitus is more likely to be associated with chronic hyperglycemia which in turn increases the likelihood of cerebral microvascular disease and may contribute to neuronal damage , brain atrophy and memory impairement. 18,19 Alternate mechanism besides vascular disease may be involved in the pathogenesis of cognitive impairment and that is amyloid beta aggregation.…”

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

“…35 A large body of epidemiological and clinical evidence in recent years has indicated that, rather than separate entities with distinct causes, VaD and AD share similar CVRFs. 36 Thus, several studies have suggested that, even in the absence of stroke, the incidence of AD is significantly influenced by the presence and severity of elevated blood pressure, [37][38][39] diabetes, 30,40 smoking, 41 and physical inactivity. 42 High cholesterol levels have been associated with increased risk of AD in a number of studies, but there are also negative reports, and these conflicting results are thought to be caused by different mediating effects of age, gender, and APOE genotype.…”

“…[24][25][26] Such conditions are now recognized as risk factors not only for vascular dementia (VaD) but also for AD. [27][28][29][30] The present article aims to critically review functional neuroimaging studies that have investigated the impact of CVRFs on brain functioning in individuals with AD and MCI, and to discuss how such findings have provided new insights about the pathophysiology of AD and MCI.…”