A professional clinical librarian searched PubMed with the following MeSH headings, combined with a Boolean “or” operator: “diabetes mellitus”, “diabetes mellitus, type 2”, “diabetes mellitus, type 1”, “diabetes complications”, “hyperglycemia”, “blood glucose”, “hypoglycemia”, or “hemoglobin A, glycosylated” (set 1) and “brain”, “cognition”, “cognition disorders”, “dementia”, “memory”, “memory disorders”, “neuropsychological tests”, “executive function”, or “psychomotor performance” (set 2).
SeriesDiabetes and cognitive dysfunction
Introduction
Around 171 million people worldwide have diabetes mellitus, and this number is estimated to double by 2030. The two primary forms of diabetes are type 1 diabetes—an autoimmune disorder characterised by an absolute or near total loss of insulin secretion—and type 2 diabetes, which is characterised by reduced insulin sensitivity and relative insulin deficiency. In both forms, chronic hyperglycaemia can lead to microvascular and macrovascular complications. Although most focus has been on end-organ disease affecting the kidney, eyes, and peripheral nervous system, the brain is also affected. Diabetes, its complications, and its treatment can induce transient or permanent cognitive abnormalities, which result from acute and chronic disturbances of blood glucose homoeostasis.
Here, we focus on diabetes-related cognitive dysfunction rather than on other related effects of diabetes on the brain, such as glucose-sensing, the regulation of whole-body glucose homoeostasis, or stroke, which have been reviewed elsewhere.1, 2 We consider the lessons learned from cognitive, neurophysiological, neuroanatomical, and neurochemical assessments of brain function in diabetes and compare results of studies of type 1 and type 2 diabetes. The increasing prevalence of diabetes and the decreasing age of diabetes diagnosis suggest that diabetes-related cognitive dysfunction will probably increase and have a substantial effect on society. Efforts to understand the pathophysiological changes that underpin the development and progression of diabetes-related cognitive dysfunction are of vital importance to develop treatments to reverse or prevent these cognitive complications.
Section snippets
Glucose control
Type 1 diabetes develops most often in childhood or adolescence and always needs insulin replacement therapy. Chronic hyperglycaemia associated with inadequate insulin replacement heightens the risk of microvascular complications such as retinopathy, neuropathy, and nephropathy.3 Intensive insulin therapy, designed to achieve near-normal glucose control, minimises the development and severity of these complications, but at the expense of increased severe hypoglycaemia (blood glucose
Cerebrovascular disease
Type 2 diabetes is a heterogeneous metabolic disorder, characterised by reduced insulin sensitivity and relative insulin deficiency. Coexisting disorders, including obesity, hypertension, and dyslipidaemia, contribute to the severity of type 2 diabetes. By contrast with type 1 diabetes, macrovascular disease causes about 80% of mortality in people with type 2 diabetes. Interventions to reduce blood glucose in people with type 2 diabetes significantly lower the risk of microvascular, and
Recommendations for clinical practice
Cognitive dysfunction associated with diabetes is mild in most instances and rarely meets criteria for clinically significant impairment, but can occur in children as well as adults and is irrespective of diabetes type. Preliminary evidence suggests that cognitive changes begin early in the disease course and can worsen over time.40 Reduction in mental efficiency might be sufficient to disrupt performance in the classroom, workplace, and home. If a patient reports that their performance in
Conclusions and future perspectives
In general, cognitive characteristics of people with type 2 diabetes are similar to those seen in people with type 1 diabetes. Both groups show evidence of mental and motor slowing (a nearly ubiquitous finding) and similar performance decrements on measures of executive functioning such as planning, attention, working memory, and problem solving (effect size is about 0·3–0·4 SD units). People with type 2 diabetes perform worse than healthy controls on learning and memory tests, unlike those
Search strategy and selection criteria
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