Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC Study

Abstract

Background: With improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age.

Methods: 1051 participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. Participants completed cognitive assessments at baseline (median age 27 years) and 2, 5, 18, and 32 years later (median age 59). HbA1c levels, frequency of severe hypoglycaemia, non-glycemic risk factors such as elevated blood pressure, and microvascular and macrovascular complications were assessed repeatedly. We examined the effects of these on measures of memory and psychomotor and mental efficiency. These studies are registered with clinicaltrials.gov, NCT00360815 (DCCT) and NCT00360893 (EDIC).

Findings: Over 32 years of follow-up, we found substantive declines in memory and psychomotor and mental efficiency. Between 18 and 32 years of follow-up, the decline in psychomotor and mental efficiency was five times larger than the change from baseline to year 18. Independent of the other risk factors and comorbidities, exposure to higher HbA1c levels, more episodes of severe hypoglycaemia, and elevated systolic blood pressure were associated with greater decrements in psychomotor and mental efficiency that was most notable by year 32 (p<0·0001). The combined effect of the presence of these three risk factors is the equivalent to an additional 9·4 years of age.

Interpretation: Cognitive function declines with ageing in type 1 diabetes. The association of glycaemia and blood pressure levels with cognitive decline suggests that better management might preserve cognitive function.

Funding: United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease.

Conflict of interest statement

Declaration of interests JAL discloses being funded by K24AG045334; consulting for vTv therapeutics; receiving royalties from Springer; and receiving a stipend from Wolters Kluwer. NC discloses personal fees and non-financial support from Eli Lilly, outside the submitted work. All other authors declare no competing interests.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Figures

Figure 1.. Changes in Cognition during DCCT/EDIC

The bars represent the changes within each of the cognitive domains between testing at DCCT baseline and each follow-up assessment, expressed as changes in z-scores and adjusted for age and sex at DCCT baseline and years of education as a time-dependent covariate. Other than a non-significant difference between years 2 and 5 for immediate memory (p=0·23) and psychomotor efficiency (p=0·49), change was significant over the years within each cognitive domain at p

Figure 2.. Changes in Psychomotor and Mental Efficiency during DCCT/EDIC at Specific Levels of A) Mean DCCT/EDIC HbA1c, B) Mean DCCT/EDIC Systolic Blood Pressure, C) Severe Hypoglycemia (Cumulative), and D) HbA1c, Systolic Blood Pressure, and Severe Hypoglycemia in Aggregate

The bars represent the model-based estimates of the mean changes in psychomotor and mental efficiency between cognitive testing at DCCT baseline and each follow-up assessment, expressed as changes in z-scores and adjusted for age and sex at DCCT baseline and years of education as a time-dependent covariate. At each study year, the mean changes in z-scores and the slope for the association between HbA1c (or systolic blood pressure) and changes in z-scores are presented. There was a significant interaction between time and HbA1c (p=0·0003) as well as between time and systolic blood pressure (p

Figure 2.. Changes in Psychomotor and Mental Efficiency during DCCT/EDIC at Specific Levels of A) Mean DCCT/EDIC HbA1c, B) Mean DCCT/EDIC Systolic Blood Pressure, C) Severe Hypoglycemia (Cumulative), and D) HbA1c, Systolic Blood Pressure, and Severe Hypoglycemia in Aggregate

The bars represent the model-based estimates of the mean changes in psychomotor and mental efficiency between cognitive testing at DCCT baseline and each follow-up assessment, expressed as changes in z-scores and adjusted for age and sex at DCCT baseline and years of education as a time-dependent covariate. At each study year, the mean changes in z-scores and the slope for the association between HbA1c (or systolic blood pressure) and changes in z-scores are presented. There was a significant interaction between time and HbA1c (p=0·0003) as well as between time and systolic blood pressure (p

Figure 2.. Changes in Psychomotor and Mental Efficiency during DCCT/EDIC at Specific Levels of A) Mean DCCT/EDIC HbA1c, B) Mean DCCT/EDIC Systolic Blood Pressure, C) Severe Hypoglycemia (Cumulative), and D) HbA1c, Systolic Blood Pressure, and Severe Hypoglycemia in Aggregate

The bars represent the model-based estimates of the mean changes in psychomotor and mental efficiency between cognitive testing at DCCT baseline and each follow-up assessment, expressed as changes in z-scores and adjusted for age and sex at DCCT baseline and years of education as a time-dependent covariate. At each study year, the mean changes in z-scores and the slope for the association between HbA1c (or systolic blood pressure) and changes in z-scores are presented. There was a significant interaction between time and HbA1c (p=0·0003) as well as between time and systolic blood pressure (p

Figure 2.. Changes in Psychomotor and Mental Efficiency during DCCT/EDIC at Specific Levels of A) Mean DCCT/EDIC HbA1c, B) Mean DCCT/EDIC Systolic Blood Pressure, C) Severe Hypoglycemia (Cumulative), and D) HbA1c, Systolic Blood Pressure, and Severe Hypoglycemia in Aggregate

The bars represent the model-based estimates of the mean changes in psychomotor and mental efficiency between cognitive testing at DCCT baseline and each follow-up assessment, expressed as changes in z-scores and adjusted for age and sex at DCCT baseline and years of education as a time-dependent covariate. At each study year, the mean changes in z-scores and the slope for the association between HbA1c (or systolic blood pressure) and changes in z-scores are presented. There was a significant interaction between time and HbA1c (p=0·0003) as well as between time and systolic blood pressure (p