Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance

Pappas, Colleen; Andel, Ross; Infurna, Frank J.; Seetharaman, Shyam

doi:10.1136/jech-2016-207588

Cited by 23 publications

(20 citation statements)

References 39 publications

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“…Consistent with our MEG/HbA 1c correlation findings, previous behavioral studies have linked deficits in working memory processing with glycemic control (35). For example, intensive regulation of glycemic control in adolescents with type 1 diabetes (36) and adults with type 2 diabetes (37) has been shown to improve working memory task performance, although there is also a risk of increased hypoglycemic episodes with intensive treatment regimens, which may again lead to worse cognitive outcomes long-term (6,37).…”

Section: Discussionsupporting

confidence: 92%

Altered Brain Dynamics in Patients With Type 1 Diabetes During Working Memory Processing

et al. 2018

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It is now generally accepted that diabetes increases the risk for cognitive impairment, but the precise mechanisms are poorly understood. A critical problem in linking diabetes to cognitive impairment is that patients often have multiple comorbidities (e.g., obesity, hypertension) that have been independently linked to cognitive deficits. In the study reported here we focused on young adults with and without type 1 diabetes who were virtually free of such comorbidities. The two groups were matched on major health and demographic factors, and all participants completed a verbal working memory task during magnetoencephalographic brain imaging. We hypothesized that patients would have altered neural dynamics in verbal working memory processing and that these differences would directly relate to clinical disease measures. Accordingly, we found that patients had significantly stronger neural responses in the superior parietal cortices during memory encoding and significantly weaker activity in parietal-occipital regions during maintenance compared with control subjects. Moreover, disease duration and glycemic control were both significantly correlated with neural responses in various brain regions. In conclusion, young healthy adults with type 1 diabetes already have aberrant neural processing relative to their peers without diabetes, using compensatory responses to perform the task, and glucose management and duration may play a central role.

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Section: Discussionsupporting

confidence: 92%

Altered Brain Dynamics in Patients With Type 1 Diabetes During Working Memory Processing

et al. 2018

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“…These results are in line with a previous systematic review by Geijselaers et al, in which HbA1c accounted for less than 10% of variance in cognition in subjects with type 2 diabetes . The strongest associations were observed in postmenopausal women with obesity, supporting a previous study with older adults in which Hb1Ac appeared more important for episodic memory performance among women than among men .…”

Section: Discussionsupporting

confidence: 92%

Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity

Arnoriaga-Rodríguez

Blasco

Coll

et al. 2019

Obesity

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Objective: Obesity has been related to later-life dementia. Serum glucose levels and insulin resistance are known to influence cognition in individuals with diabetes. This study aimed to evaluate memory function in middle-aged individuals with obesity in association with glucose metabolism and brain iron content. Methods: This was a cross-sectional case-control study including 121 participants aged 27.2 to 66.6 years (56 without obesity, 65 with obesity) stratified according to sex and menopausal status. Insulin sensitivity, body composition, brain iron content, and memory function were evaluated by euglycemic hyperinsulinemic clamp, dual-energy x-ray absorptiometry, magnetic resonance relaxometry (R2*), and California Verbal Learning Test, respectively. Results: Women with obesity, but not men, had lower scores in some California Verbal Learning Tests in association with metabolic parameters and increased brain iron content compared with controls. Fasting plasma glucose, glycated hemoglobin (HbA1c; within normal range), and R2* were negatively associated with memory scores, whereas insulin sensitivity showed positive associations. Remarkably, only HbA1c levels and R2* in the right inferior fronto-orbital region remained significant after controlling for age, sex, education, and BMI. Conclusions: Impairments in memory function in middle-aged women with obesity are associated with HbA1c levels and brain iron content independently of insulin sensitivity. These results may have implications in the design of therapeutic strategies in women with obesity.Obesity (2019) 27, 932-942.

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“…The non-significant results in our study for the global cognitive score may be explained by its derivation from a wider range of tests than used in other studies: some of the tests used showed less decline in type 2 diabetes (described further below) and hence a cancelling of effects. Studies in older age have also reported mixed results for specific cognitive domains: some have reported greater decline in verbal fluency [38] and memory [37,39] in people with type 2 diabetes, whereas several others have reported no differences [5,9,34,35,38,40]. These mixed findings most likely reflect differences in populations, follow-up times and cognitive measures.…”

Section: Discussionmentioning

confidence: 99%

“…Studies commencing in midlife and followed up over 10 years or more tend to show that type 2 diabetes is associated with faster decline in global cognitive function [3,6], processing speed [4,6], executive function [3,4], verbal fluency [6] and memory [3,4,6]. However, in older cohorts, these associations are more variable, with some showing greater decline in global cognition [5,[34][35][36], but not others [8,9,37]. The non-significant results in our study for the global cognitive score may be explained by its derivation from a wider range of tests than used in other studies: some of the tests used showed less decline in type 2 diabetes (described further below) and hence a cancelling of effects.…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study

et al. 2018

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Aims/hypothesis The aims of the study were to examine whether type 2 diabetes mellitus is associated with greater brain atrophy and cognitive decline, and whether brain atrophy mediates associations between type 2 diabetes and cognitive decline. Methods Participants without dementia aged 55-90 years from the Cognition and Diabetes in Older Tasmanians (CDOT) study underwent brain MRI (ventricular and total brain volume) and neuropsychological measures (global function and seven cognitive domains) at three time points over 4.6 years. Mixed models were used to examine longitudinal associations of type 2 diabetes with cognitive and MRI measures, adjusting for covariates. A test of mediation was used to determine whether brain atrophy explained associations between type 2 diabetes and cognitive decline. Results A total of 705 participants (diabetes: n = 348, mean age 68.2 years [SD 7.0]; no diabetes: n = 357, mean age 72.5 years [SD 7.1]) were available at baseline. Adjusting for age, sex, education and vascular risk factors, there were significant diabetes × time interactions for verbal memory (β −0.06; 95% CI −0.09, −0.02) and verbal fluency (β −0.03; 95% CI −0.06, −0.00). Although people with diabetes had lower brain (β −14.273; 95% CI −21.197, −6.580) and greater ventricular (β 2.672; 95% CI 0.152, 5.193) volumes at baseline, there were no significant diabetes × time interactions (p > 0.05) or evidence of mediation of the diabetes-cognition relationship by brain atrophy. Conclusions/interpretation In older community-dwelling people, type 2 diabetes is associated with decline in verbal memory and fluency over~5 years. The effect of diabetes on brain atrophy may begin earlier (midlife). KeywordsBrain atrophy . Brain imaging . Cognition . Dementia . Longitudinal study . Type 2 diabetes mellitus Abbreviations DBP Diastolic blood pressure SBP Systolic blood pressure WMH White matter hyperintensityElectronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-018-4778-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance

Abstract: Higher HbA1c and diabetes were both associated with declines in episodic memory, with this relationship further exacerbated by having diabetes and elevated HbA1c. HbA1c appeared more important for episodic memory performance among women than men.

Cited by 23 publications

References 39 publications

Altered Brain Dynamics in Patients With Type 1 Diabetes During Working Memory Processing

Altered Brain Dynamics in Patients With Type 1 Diabetes During Working Memory Processing

Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity

Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study

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