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Does type 2 diabetes increase rate of cognitive decline in older Mexican Americans?

ABSTRACT: Estimating effects of diabetes on cognitive change among older Mexican Americans is important, yet challenging, because diabetes and cognitive decline both predict mortality, which can induce survival bias. Older Mexican Americans in the Sacramento Area Latino Study on Aging (n=1634) completed Modified Mini-Mental State Exams (3MSE) and diabetes assessments up to 7 times (from 1998 to 2007). We examined baseline and new-onset diabetes and cognitive decline with joint longitudinal-survival models to account for death. At baseline, 32.4% of participants had diabetes and 15.8% developed diabetes during the study. During the study period, 22.8% of participants died. In joint longitudinal-survival models, those with baseline diabetes experienced faster cognitive decline (P=0.003) and higher mortality (hazards ratio=1.88; 95% confidence interval, 1.48-2.38) than those without diabetes. Cognitive decline and mortality were similar for those with new-onset diabetes and those without diabetes. For a typical person, 3MSE scores declined by 2.3 points among those without diabetes and 4.3 points among those with baseline diabetes, during the last 6 years of study. Ignoring the impact of death yielded a 17.0% smaller estimate of the effect of baseline diabetes on cognitive decline. Analyses that overlook the association between cognitive decline and mortality may underestimate the effect of diabetes on cognitive aging.

SUBMITTER: Mayeda ER

PROVIDER: S-EPMC4543443 | biostudies-literature | 2015 Jul-Sep

REPOSITORIES: biostudies-literature

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Does type 2 diabetes increase rate of cognitive decline in older Mexican Americans?

Mayeda Elizabeth R ER Haan Mary N MN Yaffe Kristine K Kanaya Alka M AM Neuhaus John J

Alzheimer disease and associated disorders 20150701 3

Estimating effects of diabetes on cognitive change among older Mexican Americans is important, yet challenging, because diabetes and cognitive decline both predict mortality, which can induce survival bias. Older Mexican Americans in the Sacramento Area Latino Study on Aging (n=1634) completed Modified Mini-Mental State Exams (3MSE) and diabetes assessments up to 7 times (from 1998 to 2007). We examined baseline and new-onset diabetes and cognitive decline with joint longitudinal-survival models ...[more]

PMID: 25650694

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Project description:Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.

Project description:BackgroundType 2 diabetes is a leading contributor to the global burden of morbidity and mortality. Ozone (O3) exposure has previously been linked to diabetes.ObjectiveWe studied the impact of O3 exposure on incident diabetes risk in elderly Mexican Americans and investigated whether outdoor physical activity modifies the association.MethodsWe selected 1,090 Mexican American participants from the Sacramento Area Latino Study on Aging conducted from 1998 to 2007. Ambient O3 exposure levels were modeled with a land-use regression built with saturation monitoring data collected at 49 sites across the Sacramento metropolitan area. Using Cox proportional hazard models, we estimated the risk of developing incident diabetes based on average O3 exposure modeled for 5-y prior to incident diabetes diagnosis or last follow-up. Further, we estimated outdoor leisure-time physical activity at baseline and investigated whether higher vs. lower levels modified the association between O3 exposure and diabetes.ResultsIn total, 186 incident diabetes cases were identified during 10-y follow-up. Higher levels of physical activity were negatively associated with incident diabetes [hazard ratio (HR)=0.64 (95% CI: 0.43, 0.95)]. The estimated HRs for incident diabetes was 1.13 (95% CI: 1.00, 1.28) per 10-ppb increment of 5-y average O3 exposure; also, this association was stronger among those physically active outdoors [HR=1.52 (95% CI: 1.21, 1.90)], and close to null for those reporting lower levels of outdoor activity [HR=1.04 (95% CI: 0.90, 1.20), pinteraction=0.01].ConclusionsOur findings suggest that ambient O3 exposure contributes to the development of type 2 diabetes, particularly among those with higher levels of leisure-time outdoor physical activity. Policies and strategies are needed to reduce O3 exposure to guarantee that the health benefits of physical activity are not diminished by higher levels of O3 pollution in susceptible populations such as older Hispanics. https://doi.org/10.1289/EHP8620.

Project description:AimsCognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60?years; diabetes duration, 11?years) from the Veterans Affairs Diabetes Trial.MethodsA battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5. Thirty-seven risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses.ResultsThe mean age-adjusted DSym or TMT-B declined significantly in all study participants (P?<?0.001). Randomized INT glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta?=?-0.028; P?=?0.0057), lower baseline diastolic blood pressure (BP; beta?=?0.028; P?=?0.002), and baseline calcium channel blocker medication use (beta?=?-0.639; P?<?0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic BPs. Baseline thiazide diuretic use (beta?=?-0.549; P?=?0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic BP-lowering was significantly associated (P?<?0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride-lowering (P?=?0.045) and decline in digit symbol substitution task performance.ConclusionA 5-year period of randomized INT glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic BPs as well as plasma triglycerides appeared as modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.

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Does type 2 diabetes increase rate of cognitive decline in older Mexican Americans?

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Does type 2 diabetes increase rate of cognitive decline in older Mexican Americans?

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