Elsevier

The Lancet

Volume 379, Issue 9833, 16–22 June 2012, Pages 2291-2299
The Lancet

Series
Diabetes and cognitive dysfunction

https://doi.org/10.1016/S0140-6736(12)60360-2Get rights and content

Summary

Cognitive dysfunction in type 1 and type 2 diabetes share many similarities, but important differences do exist. A primary distinguishing feature of type 2 diabetes is that people with this disorder often (but not invariably) do poorly on measures of learning and memory, whereas deficits in these domains are rarely seen in people with type 1 diabetes. Chronic hyperglycaemia and microvascular disease contribute to cognitive dysfunction in both type 1 and type 2 diabetes, and both disorders are associated with mental and motor slowing and decrements of similar magnitude on measures of attention and executive functioning. Additionally, both types are characterised by neural slowing, increased cortical atrophy, microstructural abnormalities in white matter tracts, and similar, but not identical, changes in concentrations of brain neurometabolites. Disconcertingly, the rapid rise in obesity and type 2 diabetes in all age groups might result in a substantial increase in prevalence of diabetes-related 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

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).

References (81)

  • The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

    N Engl J Med

    (1993)
  • Hypoglycemia in the diabetes control and complications trial

    Diabetes

    (1997)
  • AMA Brands et al.

    The effects of type 1 diabetes on cognitive performance: a meta-analysis

    Diabetes Care

    (2005)
  • AM Patiño-Fernández et al.

    Neurocognitive functioning in preschool-age children with type 1 diabetes mellitus

    Pediatr Diabetes

    (2010)
  • EA Northam et al.

    Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset

    Diabetes Care

    (2001)
  • CM Ryan

    Diabetes and brain damage: more (or less) than meets the eye?

    Diabetologia

    (2006)
  • C Ryan et al.

    Cognitive deficits in adolescents who developed diabetes early in life

    Pediatrics

    (1985)
  • T Brismar et al.

    Loss of temporal lobe beta power in young adults with type 1 diabetes mellitus

    Neuroreport

    (2002)
  • L Hyllienmark et al.

    EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes

    Diabetologia

    (2005)
  • E van Duinkerken et al.

    Functional brain connectivity and neurocognitive functioning in patients with long-standing type 1 diabetes with and without microvascular complications: a magnetoencephalography study

    Diabetes

    (2009)
  • A Dejgaard et al.

    Evidence for diabetic encephalopathy

    Diabetic Med

    (1991)
  • MA Salem et al.

    Single photon emission tomography (SPECT) study of regional cerebral blood flow in normoalbuminuric children and adolescents with type 1 diabetes

    Pediatr Diabetes

    (2002)
  • JF Jiménez-Bonilla et al.

    Assessment of cerebral perfusion and cerebrovascular reserve in insulin-dependent diabetic patients without central neurological symptoms by means of 99mTc-HMPAO SPET with acetazolamide

    Eur J Nucl Med

    (2001)
  • R Quirce et al.

    Semi-quantitative assessment of cerebral blood flow with 99mTc-HMPAO SPET in type 1 diabetic patients with no clinical history of cerebrovascular disease

    Eur J Nucl Med

    (1997)
  • AM Jacobson et al.

    Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort

    Diabetologia

    (2011)
  • G Musen et al.

    Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry

    Diabetes

    (2006)
  • AM Wessels et al.

    Voxel-based morphometry demonstrates reduced gray matter density on brain MRI in patients with diabetic retinopathy

    Diabetologia

    (2006)
  • CT Kodl et al.

    Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function

    Diabetes

    (2008)
  • DT Franc et al.

    High connectivity between reduced cortical thickness and disrupted white matter tracts in long-standing type 1 diabetes

    Diabetes

    (2011)
  • IK Lyoo et al.

    Altered prefrontal glutamate-glutamine-gamma-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus

    Arch Gen Psychiatry

    (2009)
  • S Mäkimattila et al.

    Brain metabolic alterations in patients with type 1 diabetes-hyperglycemia-induced injury

    J Cereb Blood Flow Metab

    (2004)
  • AE Gold et al.

    Recurrent severe hypoglycaemia and cognitive function in type 1 diabetes

    Diabetic Med

    (1993)
  • I Deary et al.

    Severe hypoglycemia and intelligence in adult patients with insulin-treated diabetes

    Diabetes

    (1993)
  • AM Jacobson et al.

    Long-term effects of diabetes and its treatment on cognitive function

    N Engl J Med

    (2007)
  • T Aye et al.

    The feasibility of detecting neuropsychologic and neuroanatomic effects of type 1 diabetes in young children

    Diabetes Care

    (2011)
  • BO Asvold et al.

    Cognitive function in type 1 diabetic adults with early exposure to severe hypoglycemia: a 16-year follow-up study

    Diabetes Care

    (2010)
  • Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

    Lancet

    (1998)
  • AR Folsom et al.

    Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke

    Diabetes Care

    (1999)
  • E Selvin et al.

    Cardiovascular outcomes in trials of oral diabetes medications: a systematic review

    Arch Intern Med

    (2008)
  • MWJ Strachan et al.

    Is type 2 (non-insulin dependent) diabetes mellitus associated with an increased risk of cognitive dysfunction?

    Diabetes Care

    (1997)
  • Cited by (693)

    View all citing articles on Scopus
    View full text