The Effect of Type 2 Diabetes on Cognitive Function in Middle-Aged Patients

Could midlife cognitive function decline be an indicator of increased dementia risk in patients with type 2 diabetes?

Patients with type 2 diabetes are at an increased risk of developing dementia, mainly middle-aged patients. Previous studies have found that middle-aged patients with type 2 diabetes risk accelerated cognitive decline dependent on glycemic control and disease duration. However, few studies have investigated the association between midlife cognitive function and type 2 diabetes; therefore, it is unknown whether cognitive decline is present in middle-aged type 2 diabetes patients. Therefore, a. H. Dyer et al. examined the association between objective cognitive impairment and midlife type 2 diabetes.

This cross-sectional study analyzed baseline data from the Exploring Novel Biomarkers of Brain Health in Diabetes (ENBRIND) study, a longitudinal cohort study observing patients’ cognition with type 2 diabetes. Participant cognitive function was assessed using two tools, the Montreal Cognitive Assessment (MoCA) test and a custom battery created based on the Cambridge Neuropsychological Assessment Battery. The custom battery included six tests assessing spatial working memory, delayed pattern recognition, rapid visual processing, One Touch stockings of Cambridge, reaction time, and paired associates learning.

This analysis included individuals between the ages of 35 – 65 years with or without type 2 diabetes. Patients were excluded from the study if they had any of the following: non-type 2 diabetes, macro- or microvascular complications of T2D, medical conditions that can affect cognitive function, significant cardiac, respiratory, or musculoskeletal comorbidities and diagnosis of cognitive impairment, dementia, an axis I psychiatric, or neurologic disorder.

Participants were recruited at a 2:1 ratio for individuals with vs. without T2D. Baseline characteristics were assessed in all participants, including demographics, medical history, and daily medication use. Patients in the midlife type 2 diabetes group had higher BMIs, A1c levels, and a higher prevalence of hypertension and hyperlipidemia than patients without diabetes. On average, patients had a confirmed diabetes diagnosis for six years.

One hundred fifty-two participants were included in the study: 102 patients with type 2 diabetes and 50 normoglycemic controls. Patients with T2D were over two times more likely to produce errors on the MoCA after an adjustment than normoglycemic patients (adjusted IRR 2.09; 95% CI 1.49 – 2.93, p< 0.001). The subdomains of MoCA were also analyzed, and it was reported that patients with T2D were more likely to produce errors in the domains related to attention (p = 0.011), visuospatial/executive function (p = 0.003), and delayed memory (p = 0.031). 

While all 50 normoglycemic controls completed the neuropsychological assessment, three patients in the type 2 diabetes group did not complete or only partially completed the assessment due to either early termination of testing or technical difficulties. The memory composite scores were significantly lower in patients with type 2 diabetes than in the control group (β -0.21; 95% CI -0.42 to -0.01, p = 0.04). Only one individual domain of the assessment, the paired associates learning task, showed a significant reduction in score in participants with T2D (β -2.21; 95% CI -3.86 to -0.55, p = 0.01).

A. H. Dyer et al. found an association between type 2 diabetes and objective cognitive impairment in middle-aged individuals, though the data may not be clinically significant. They also reported that their findings complemented previous structural neuroimaging research in patients with T2D by showing an association between reduced scoring on the paired associates learning task and reduced volume of brain regions that target that task. This association could be used to identify individuals at an increased risk of cognitive impairment in the future, which could be particularly important when it comes to interventions to prevent cognitive decline. Though this was a cross-sectional study, the authors aim to evaluate the long-term effects of cognitive decrements in patients with T2D on later cognitive decline in the future.

Practice Pearls:

• Mid-life type 2 diabetes was found to be associated with lower scores on general cognitive function tests.
• The findings of the study complemented previous structural neuroimaging research in patients with T2D.
• Early cognitive decrement can act as an indicator for individuals at an increased risk of cognitive impairment in the future.

Tuligenga, Richard H, et al. “Midlife Type 2 Diabetes And Poor Glycaemic Control As Risk Factors For Cognitive Decline In Early Old Age: A Post-Hoc Analysis Of The Whitehall II Cohort Study”. Lancet, 2020.

Dyer, A. H. et al. “Cognitive Performance In Midlife Type 2 Diabetes: Results From The ENBIND Study”. Diabetic Medicine, 2020. Wiley

Destiny Reed, PharmD. Candidate, Florida A&M College of Pharmacy and Pharmaceutical Sciences