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Diabetes and Cognition: Free white paper

Posted on 23 January 2015 in Clinical Trials

Key Points:

  • Diabetes and it’s treatments can impact the brain and affect cognitive function.
  • The safety of treatments that alter glucose levels in the brain and affect neural networks needs to be established as they may result in chronic cognitive deficits.
  • A reliable and sensitive cognitive assessment tool is required to evaluate the magnitude of cognitive dysfunction associated with diabetes and the treatment thereof.
  • Cantab tests assess memory, executive function and processing speed and have shown sensitivity to cognitive dysfunction associated with diabetes, its treatments and risk factors associated with the disease. 

Disorder-specific impairments and treatment-induced effects on cognitive function

Diabetes mellitus is defined by high blood glucose concentrations and the body’s inability to regulate these concentrations properly. Diabetes is a complex disorder and several factors, either related to the disease itself or treatment thereof, can impact the brain and affect cognitive function.

Download the Diabetes and Cognition white paper

Type 1 (insulin dependent) diabetes accounts for 5–10% of patients with diabetes and typically develops in childhood or early adulthood; in most patients, the age of onset is younger than 30 years. There is compelling evidence that children with type 1 diabetes demonstrate pathology-related cognitive impairment and perform worse at school compared to age-matched healthy children; sizeable cognitive deficits in children with type 1 diabetes have been reported in measures of attention, processing speed, memory and executive functions (Biessels 2008; Desrocher 2004), though the magnitude and specificity of these impairments vary. Desrocher (2004) found that cognitive impairments are highly dependent on the neurodevelopmental stage children are at when the disease first manifests or fluctuations of blood glucose levels occur.

A delicate balance

There are currently no treatments that are shown to ameliorate the observed cognitive impairments in patients with diabetes. Type 1 diabetes is primarily treated with insulin in an attempt to achieve normo-glycaemia and decrease the risk of comorbid complications. Insulin crosses the blood-brain barrier and affects the central nervous system, giving it the potential to modulate a range of cognitive functions (Ryan, 2006). Improving patients’ glycaemic control has been associated with improved cognitive function (Ryan, 2006, see Figure 1); however intensive treatment with insulin increases the risk of hypoglycaemic episodes (The Diabetes Control and Complications Study Group (DCCT), 1993; 2007). The adverse effects of repeated and severe episodes of hypoglycaemia on the central nervous system might be an important mediator of the so-called “early-onset effect” of diabetes, although hypoglycaemic episodes can also affect intellectual development in older children and adolescents (Biessels, 2008). The safety of treatments that alter glucose levels in the brain and affect these neural networks needs to be established as they may result in chronic cognitive deficits that persist into adulthood.

Figure 1. Improving glycaemic control with an insulin sensitizer reduces the number of errors made on an episodic memory task (Cantab Paired Associates Learning (PAL)).

Risk of late-life cognitive impairment in type 2 diabetes

Prevalence of type 2 diabetes is greater in older adult populations and is thus associated with late-life cognitive impairment. This tends to be manifested by a moderate increase in age-related decline, as well as an increased risk for vascular dementia, stroke and other dementia related diseases (Biessels, 2005; Biessels, 2006; Cuikerman, 2005). Studies have reported that patients with diabetes demonstrate slower processing speed and impaired executive function compared to healthy individuals, which may be mediated through cerebrovascular pathology (Qui, 2013; Cukierman, 2005).

Similarly to type 1 diabetes, adverse effects of hyperglycaemic episodes and insulin resistance may also be factors associated with the cognitive dysfunction observed in individuals with type 2 diabetes. A review of observational studies reported that patients with impaired glucose tolerance experience a greater magnitude of cognitive decline than those without, supporting the link between hyperglycaemia and cognitive dysfunction (Cukierman, 2005).

Other than insulin regulation, treatment options for type 2 diabetes include changes in diet and exercise; decreased fat tissue and increased muscle mass lead to better glucose absorption. Maintaining long-term control of diabetes by monitoring these types of factors may decrease the risk of late-life cognitive impairments. Hypoglycaemic drugs are also prescribed to improve patients’ glycaemic control either by increasing insulin production or reducing glucose output. Studies have indicated that glucose-lowering medication and level of glycaemic control may modulate the risk of cognitive impairment in older adults with type 2 diabetes (Ryan, 2006). Conversely, other research has not found an association between medication and cognitive function (Saczynski, 2008). The variance in the relationship between diabetes medication and cognition indicates the need for larger-scale, longitudinal studies to establish the relative safety and impact of treatments being developed for diabetes.

Addressing the growing concern

 

The incidence and prevalence of diabetes vary across countries and are expected to increase during the coming decades owing to the influence of lifestyle and socioeconomic factors. Therefore a reliable and sensitive cognitive assessment tool is required to evaluate the magnitude of cognitive dysfunction associated with diabetes and treatment thereof. Cantab tasks assessing domains of memory, executive function and processing speed have shown sensitivity to cognitive dysfunction associated with diabetes, its treatment and risk factors associated with the disease.

Determining the safety of a compound can be complex and challenging, from both a scientific and an operational perspective. Our Clinical Trial Information Systems, CTIS-Profile and CTIS-Profile 2+ are designed to support the assessment of compounds for cognitive safety throughout all phases of drug development. The CTIS products are delivered on the Cantab Connect platform, combining leading cognitive neuroscience with innovative cloud technology enabling more reliable and sensitive cognitive testing. CTIS-Profile and CTIS-Profile 2+ target key cognitive domains commonly affected by pharmacological manipulation, including psychomotor processing speed, visual episodic memory, working memory and executive function. The touchscreen assessment tools offer automated administration and scoring to reduce workloads and optimize productivity and are regulatory approved and designed for GCP compliant studies. Clean and reliable data is guaranteed with Cantab science and data management built into every CTIS product.