Executive Function and Diabetes: A Clinical Neuropsychology Perspective

This review was aimed at systematically investigating the evidence suggesting that obese individuals demonstrate impaired performance on behavioural tasks examining executive functioning abilities. A systematic review of literature was carried out by searching five separate databases (PsycINFO, MEDLINE, EMBASE, CINAHL and PubMed) and a hand search of relevant journals. Twenty-one empirical papers were identified from the search criteria and the results were considered in relation to different executive functioning domains. There is little consistency of results both within and across different domains of executive functioning. The review suggests that obese individuals show difficulties with decision-making, planning and problem-solving when compared to healthy weight controls, with fewer difficulties reported on tasks examining verbal fluency and learning and memory. A lack of replication and underreporting of descriptive data is a key limitation of studies in this area and further research is needed to examine the mechanisms underpinning the relationship between obesity and executive functioning.

Aims/hypothesis The aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. Methods Data from wave 2 (2004–2005) to wave 7 (2014–2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3–7. Linear mixed models were used to evaluate longitudinal associations. Results The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6–13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (−0.0009 SD/year, 95% CI −0.0014, −0.0003), memory z scores (−0.0005 SD/year, 95% CI −0.0009, −0.0001) and executive function z scores (−0.0008 SD/year, 95% CI −0.0013, −0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by −0.012 SD/year (95% CI −0.022, −0.002) and −0.031 SD/year (95% CI −0.046, −0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. Conclusions/interpretation Significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-017-4541-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes). This article attempts to relate these findings to the development of critical neuropathological hallmarks of the disease. Recent work reveals that hyperglycemia in diabetes triggers nutrient excess in neurons that, in turn, mediates a phenotypic change in mitochondrial biology through alteration of the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling axis. This vital energy sensing metabolic pathway modulates mitochondrial function, biogenesis and regeneration. The bioenergetic phenotype of mitochondria in diabetic neurons is aberrant due to deleterious alterations in expression and activity of respiratory chain components as a direct consequence of abnormal AMPK/PGC-1α signaling. Utilization of innovative respirometry equipment to analyze mitochondrial function of cultured adult sensory neurons from diabetic rodents shows that the outcome for cellular bioenergetics is a reduced adaptability to fluctuations in ATP demand. The diabetes-induced maladaptive process is hypothesized to result in exhaustion of the ATP supply in the distal nerve compartment and induction of nerve fiber dissolution. The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich ataxia, Charcot-Marie-Tooth disease type 2 and human immunodeficiency virus-associated distal-symmetric neuropathy. Copyright © 2012 Elsevier Inc. All rights reserved.