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Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which leads to multidimensional cognitive deficits and wildly spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back, but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM.

SUBMITTER: He XS

PROVIDER: S-EPMC4416650 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics.

He Xiao-Song XS Wang Zhao-Xin ZX Zhu You-Zhi YZ Wang Nan N Hu Xiaoping X Zhang Da-Ren DR Zhu De-Fa DF Zhou Jiang-Ning JN

Acta diabetologica 20140704 1

Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which leads to multidimensional cognitive deficits and wildly spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly diagnosed middle-a ...[more]

PMID: 24993663

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Project description:ObjectiveThe apolipoprotein E ε4 (APOE ε4) allele and midlife obesity are independent risk factors for Alzheimer's disease (AD). Both of these risk factors are also associated with differences in brain activation, as measured by blood oxygenation level-dependent (BOLD) responses, in the absence of detectable cognitive deficits. Although the presence of these risk factors may influence brain activity during working memory tasks, no study to date has examined whether the presence of the ε4 allele explains variation in working memory brain activity while matching for levels of overweight/obesity. The primary aim of this study was to determine whether the presence of the ε4 allele is associated with differences in task-functional magnetic resonance imaging (fMRI) brain activation in adults with overweight/obesity. We predicted that ε4 carriers would have greater brain activation in regions that support working memory.MethodsThis ancillary study included 48 (n = 24 APOE ε4 carriers; n = 24 APOE ε4 non-carriers), sedentary middle-aged adults (Mean age = 44.63 ± 8.36 years) with overweight/obesity (Mean BMI = 32.43 ± 4.12 kg/m2) who were matched on demographic characteristics. Participants were a subsample enrolled in 12-month randomized clinical trial examining the impact of energy-restricted diet and exercise on cardiovascular health outcomes. Participants completed a n-back working memory task with fMRI, which were completed within one month of the start of the intervention. Participants also underwent pseudo-continuous arterial spin labeling scans, a MRI measure of cerebral blood flow (CBF).ResultsCompared to non-ε4 carriers with overweight/obesity, ε4 carriers with overweight/obesity had lower fMRI brain activity in the middle frontal gyrus, pre and post central gyrus, supramarginal gyrus, superior temporal gyrus, lateral occipital cortex, and angular gyrus (z range = 2.52-3.56) during the n-back working memory task. Differences persisted even when controlling for CBF in these brain regions.ConclusionThese results indicate that presence of the APOE ε4 allele in middle-aged adults with overweight/obesity is related to altered brain activity during a working memory paradigm, which may confer risk for accelerated neurocognitive decline in late adulthood. Future research is needed to clarify the clinical implications of these findings in the context of risk for AD.

Project description:BackgroundPhysical activity (PA) is a promising method to improve cognition among middle-aged and older adults. Latinos are at high risk for cognitive decline and engaging in low levels of PA. Culturally relevant PA interventions for middle-aged and older Latinos are critically needed to reduce risk of cognitive decline. We examined changes in cognitive performance among middle-aged and older Latinos participating in the BAILAMOS™ dance program or a health education group and compared the mediating effects of PA between group assignment and change in cognitive domains.MethodsOur 8-month randomized controlled trial tested BAILAMOS™, a 4-month Latin dance program followed by a 4-month maintenance phase. A total of 333 older Latinos aged 55+ were randomized to either BAILAMOS™, or to a health education control group. Neuropsychological tests were administered, scores were converted to z-scores, and specific domains (i.e., executive function, episodic memory, and working memory) were derived. Self-reported PA was assessed, and we reported categories of total PA, total leisure PA, and moderate-to-vigorous PA as minutes/week. A series of ANCOVAs tested changes in cognitive domains at 4 and 8 months. A mediation analysis tested the mediating effects of each PA category between group assignment and a significant change in cognition score.ResultsThe ANCOVAs found significant improvement in working memory scores among participants in the dance group at month 8 [F (1,328) = 5.79, p = 0.017, d = 0.20], but not in executive functioning [F (2,328) = 0.229, p = 0.80, Cohen's d = 0.07] or episodic memory [F (2,328) = 0.241, p = 0.78, Cohen's d = 0.05]. Follow-up mediation models found that total PA mediated the relationship between group assignment and working memory, in favor of the dance group (β = 0.027, 95% CI [0.0000, 0.0705]). Similarly, total leisure PA was found to mediate this relationship [β = 0.035, 95% CI (0.0041, 0.0807)].ConclusionA 4-month Latin dance program followed by a 4-month maintenance phase improved working memory among middle-aged and older Latinos. Improvements in working memory were mediated by participation in leisure PA. Our results support the current literature that leisure time PA influences cognition and highlight the importance of culturally relevant PA modalities for Latinos.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT01988233].

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Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics.

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Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics.

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