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      High-normal blood glucose levels may be associated with decreased spatial perception in young healthy adults

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          Abstract

          The negative effects of high normal glucose on cognitive function were previously reported in euglycemic individuals of middle age and the elderly population. This study aimed at examining the effect of baseline blood glucose levels on spatial ability, specifically verticality perception on the computerized rod and frame test (CRFT) in young healthy adults. 63 healthy male medical students (age range from 18–23 years), of whom 30 were non-fasting outside the month of Ramadan and 33 fasting during Ramadan of the year 2016, were recruited in order to create varying degrees of glycemia during which verticality perception was carried out. Baseline blood glucose reading was obtained prior to commencing the CRFT test. Blood glucose levels at the time of testing decreased as the duration between the last meal and testing increased. A blood glucose range of 62–117 mg/dl was achieved among participants for this study. Linear regression analysis showed that blood glucose level at testing correlated positively with all alignment spatial error parameters, indicating a probable reduction of spatial perception ability with higher blood glucose levels. These results are consistent with other cognitive studies in older healthy humans and emphasize the critical impact of early glucose dys-homeostasis on cognitive function. They also indicate that elevated blood glucose may affect cognitive functioning outside of the usual complications of diabetes.

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          Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

          For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.
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            Cognitive demand and blood glucose.

            Previous research has identified that glucose administration can enhance cognitive performance, especially during more intense cognitive processing. There appears to be a reciprocal relationship between falling glucose levels and cognitive performance, particularly under conditions of cognitive demand. The present placebo-controlled, double-blind, balanced, crossover study examined the possibility that a high cognitive load may produce changes in blood glucose levels. A secondary aim was to examine the effects of glucose on tasks of varying cognitive demand load. The effects of a glucose drink on participants' performance of a serial subtraction task (computerised Serial Sevens), a somatically matched control task (key-pressing), a short interval Word Memory task and a Word Retrieval (Verbal Fluency) task were assessed. The change in blood glucose during the demanding computerised Serial Sevens was compared to the change occurring during the key-pressing control. Glucose consumption significantly improved performance on Serial Sevens, with a trend for improved performance on Word Retrieval and no effect on the Word Memory task. Compared with the control task, Serial Sevens resulted in a significant reduction in blood glucose in both drink conditions. This accelerated decay was significantly greater following glucose than placebo. It is suggested that the amount of cognitive load associated with task performance is an index of its sensitivity to enhancement by glucose. Furthermore, a period of intense cognitive processing leads to a measurable decrease in levels of peripherally measured blood glucose, which may be linked to increased neural energy expenditure. However, the relative contribution of central and peripheral (e.g. cardiac) activity to this effect has yet to be determined.
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              Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging.

              Type 2 diabetes is becoming increasingly common in most Westernized countries and it now occurs at a younger age. There are pathologies associated with diabetes, mostly systemic ones. However, a growing number of studies is also showing that diabetes is associated with impaired cognitive processes in older adults and hasten the progression to dementia. The most common cognitive deficits are decreases in processing speed and verbal memory; these may extend to other aspects of cognition with increasing age. The link between diabetes and cognitive decline is obscured by depression, hypertension, as well as cardio- and cerebrovascular diseases, all of which occur to varying degrees in diabetic patients. A few studies indicate that controlling blood glucose with anti-diabetic treatments may help prevent the cognitive decline in diabetic patients before they are 70 years old. After that age, diabetes appears to produce faster cognitive decline and may increase the occurrence of pathological changes associated with vascular dementia or Alzheimer's disease.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – original draft
                Role: Data curationRole: InvestigationRole: Writing – original draft
                Role: Data curationRole: Formal analysis
                Role: Formal analysisRole: InvestigationRole: SoftwareRole: Validation
                Role: ConceptualizationRole: InvestigationRole: Validation
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 June 2018
                2018
                : 13
                : 6
                : e0199051
                Affiliations
                [1 ] Department of Physiology, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain
                [2 ] College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain
                [3 ] Faculty of Health and Social Sciences, Bournemouth University, Fern Barrow, Poole, Dorset, United Kingdom
                [4 ] School of Health and Social Care, Bournemouth University, Fern Barrow, Poole, Dorset, United Kingdom
                Weill Cornell Medical College Qatar, QATAR
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-2994-5150
                http://orcid.org/0000-0002-3590-710X
                Article
                PONE-D-18-04160
                10.1371/journal.pone.0199051
                6002080
                29902276
                2e341c70-aedd-4852-8e3d-9462ab066ea5
                © 2018 Razzak et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 February 2018
                : 30 May 2018
                Page count
                Figures: 4, Tables: 1, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100009606, Arabian Gulf University;
                Award Recipient :
                The Arabian Gulf University provided the funding for buying the software and other material require for this study.
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