We searched PubMed from Jan 1, 1990, to May 15, 2014, with the terms (and synonyms) “dementia”, “Alzheimer's disease”, “cognitive impairment”, “diabetes”, and “metabolic syndrome”, in combination with the key terms “epidemiology”, “risk factors”, “brain MRI”, “prevention”, “diagnosis”, “treatment”, and “screening”. We only searched for papers published in English. We also searched reference lists of papers identified and extracted relevant papers from our records. Furthermore, we searched //ClinicalTrials.gov
Personal ViewCognitive function in patients with diabetes mellitus: guidance for daily care
Introduction
Diabetes mellitus is a common metabolic disorder that can lead to chronic complications such as cardiovascular disease, nephropathy, retinopathy, and peripheral neuropathy. Both type 1 and type 2 diabetes are characterised by hyperglycaemia, but their pathophysiology, associated comorbidities, and epidemiology are different (table 1). Type 1 diabetes accounts for 5–10% of diabetes cases and mostly develops in childhood or early adulthood.1 Type 2 diabetes is caused by insulin resistance, which is often related to obesity, but also involves progressive β-cell dysfunction.2 Type 2 diabetes is typically a disease of older age, although its incidence has increased in young adults and even in adolescents during the past two decades.3 The worldwide prevalence of diabetes has increased during the past five decades, with 382 million people with diabetes in 2013, and is likely to increase further, making diabetes and its complications important public health issues.4
Awareness is increasing of subtle structural and functional cerebral changes in patients with diabetes, which can manifest in cognitive dysfunction. This increasing awareness is shown by a steady increase in publications about topics ranging from detailed cognitive testing and advanced brain imaging to epidemiological surveys. However, little guidance is available for the application of available knowledge about the daily clinical management of cognitive dysfunction in patients with diabetes. In this Personal View, we provide a framework that links different stages of cognitive dysfunction in type 1 and type 2 diabetes with brain-imaging abnormalities, risk factors, and treatment options. Additionally, we address the issues surrounding early identification of patients at increased risk of accelerated cognitive decline, and suggest possible therapeutic approaches.
Section snippets
Cognitive function
Neuropsychological studies in patients with type 1 diabetes consistently report subtle changes in cognitive function compared with individuals without diabetes, particularly in general intelligence, psychomotor speed, and mental flexibility. In a systematic review,5 performance on these domains in adult patients was on average half an SD (0·3–0·7 SDs) below that of people without diabetes. Additionally, overall cognition and the visual perception domain were slightly affected (0·3–0·4 SDs less
Cognitive function
Compared with people without diabetes, patients with type 2 diabetes perform slightly worse on a range of cognitive tasks. For memory, processing speed, and executive function, cognitive performance is on average 0·3–0·4 SDs lower than that of people without diabetes.24, 25 These subtle changes in cognitive performance have been reported from adolescence26 up to the age of 80 years (figure 1). Because several domains are affected in patients with type 2 diabetes, a diminished ability to
Classification of stages of cognitive dysfunction
The data discussed in the preceding sections show that diabetes is associated with changes in cognitive function, ranging from subtle cognitive changes to MCI and dementia. In our view, differentiation between these different stages of cognitive dysfunction in clinical practice is essential, because they are likely to have a different prognosis and might need different management (panel 1).6
The same diagnostic criteria apply to cognitive impairment—ie, MCI and dementia—in people with diabetes
Cognitive impairment
No specific treatments exist for people with diabetes and MCI or dementia, and clinicians should treat MCI or dementia according to the same principles as in people without diabetes. Nevertheless, cognitive dysfunction in patients with diabetes is associated with poor glycaemic control93—especially in the case of impaired executive function94—with an increased frequency of hospital admissions and with an increased occurrence of severe hypoglycaemic episodes.72 Therefore, diagnosis of cognitive
Future perspectives
Awareness of diabetes-associated cognitive dysfunction is increasing. However, important questions still need to be answered. Should cognitive impairment be routinely screened for in patients with diabetes, just like other diabetic complications? Can people at risk of accelerated cognitive decline be identified at an early stage, and how should these people be treated to prevent deterioration?
Conclusions
Diabetes is linked to different stages of cognitive dysfunction, ranging from diabetes-associated cognitive decrements to dementia. These stages are not necessarily part of one continuous process, and might have different prognoses. Moreover, different stages need different management. We present a framework that helps to distinguish between different stages of cognitive dysfunction in patients with diabetes. No treatment exists to reduce or prevent diabetes-associated cognitive dysfunction,
Search strategy and selection criteria
References (103)
Type 1 diabetes
Lancet
(2006)- et al.
Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
Lancet
(2014) - et al.
Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions
Lancet Diabetes Endocrinol
(2014) - et al.
Cognition and diabetes: a lifespan perspective
Lancet Neurol
(2008) - et al.
Frontal gray matter atrophy in middle aged adults with type 1 diabetes is independent of cardiovascular risk factors and diabetes complications
J Diabetes Complications
(2013) - et al.
Predictors of cognitive impairment in type 1 diabetes
Psychoneuroendocrinology
(2007) - et al.
Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: a systematic comparison of their impact on cognition
Biochim Biophys Acta
(2009) - et al.
Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review
Neurosci Biobehav Rev
(2009) - et al.
Intensive multifactorial treatment and cognitive functioning in screen-detected type 2 diabetes—the ADDITION-Netherlands study: a cluster-randomized trial
J Neurol Sci
(2012) - et al.
Association of diabetes with amnestic and nonamnestic mild cognitive impairment
Alzheimers Dement
(2014)
The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Alzheimers Dement
Risk of dementia in diabetes mellitus: a systematic review
Lancet Neurol
Alzheimer's disease
Lancet
Insulin, cognition, and dementia
Eur J Pharmacol
Human cerebral neuropathology of Type 2 diabetes mellitus
Biochim Biophys Acta
Diabetes mellitus and progression of vascular brain lesions and brain atrophy in patients with symptomatic atherosclerotic disease. The SMART-MR study
J Neurol Sci
Diabetes, hyperglycaemia, and acute ischaemic stroke
Lancet Neurol
Structural brain imaging in diabetes: a methodological perspective
Eur J Pharmacol
Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: a cohort study
Lancet Diabetes Endocrinol
Antihypertensive drug use and the risk of dementia in patients with diabetes mellitus
Alzheimers Dement
Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review
Eur J Pharmacol
Depression and type 2 diabetes: a causal association?
Lancet Diabetes Endocrinol
Mild depressive symptoms do not influence cognitive functioning in patients with type 2 diabetes
Psychoneuroendocrinology
Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy
Lancet Neurol
Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies
Lancet Neurol
Revising the definition of Alzheimer's disease: a new lexicon
Lancet Neurol
A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
Alzheimers Dement
Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study
Diabetes Res Clin Pract
National Diabetes Fact Sheet
IDF Diabetes Atlas
The effects of type 1 diabetes on cognitive performance: a meta-analysis
Diabetes Care
Cognitive performance, psychological well-being, and brain magnetic resonance imaging in older patients with type 1 diabetes
Diabetes
Cognitive function in children with type 1 diabetes: a meta-analysis
Diabetes Care
Long-term effect of diabetes and its treatment on cognitive function
N Engl J Med
Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications
Diabetologia
Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes
Diabetes
Central nervous system function in youth with type 1 diabetes 12 years after disease onset
Diabetes Care
Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function
Diabetes Care
High connectivity between reduced cortical thickness and disrupted white matter tracts in long-standing type 1 diabetes
Diabetes
Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function
Diabetes
Resting-state brain networks in type 1 diabetic patients with and without microangiopathy and their relation to cognitive functions and disease variables
Diabetes
Network-level structural abnormalities of cerebral cortex in type 1 diabetes mellitus
PLoS One
The effects of type 1 diabetes on cerebral white matter
Diabetologia
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
Effects of intensive diabetes therapy on neuropsychological function in adults in the Diabetes Control and Complications Trial
Ann Intern Med
Magnitude of cognitive dysfunction in adults with type 2 diabetes: a meta-analysis of six cognitive domains and the most frequently reported neuropsychological tests within domains
J Int Neuropsychol Soc
Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus
Diabetologia
A detailed profile of cognitive dysfunction and its relation to psychological distress in patients with type 2 diabetes mellitus
J Int Neuropsychol Soc
Selective review of cognitive aging
J Int Neuropsychol Soc
Metabolic syndrome, cognitive performance, and dementia
J Alzheimers Dis
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