The Association of Duration of Type 2 Diabetes with Cognitive Performance is Modulated by Long-Term Glycemic Control

Abstract

Objectives It is unclear why duration of type 2 diabetes (T2D) is associated with increased cognitive compromise. High hemoglobin A1c (HbA1c) has also been associated with dementia, and is the primary contributor to T2D complications. Here we investigated whether the association of duration of T2D with cognitive functioning is modulated by hemoglobin A1C levels. Methods This study examined non-demented community dwelling T2D elderly (n=897) participating in the Israel Diabetes and Cognitive Decline study, who were assessed with a broad neuropsychological battery. Subjects were all from the Maccabi Healthcare Services which has a Diabetes Registry with complete HbA1c measurements since 1998. Partial correlations were performed to examine the modulating effect of HbA1c on the relationship of duration of T2D with five cognitive measures, controlling for sociodemographic and cardiovascular risk factors. Results An interaction of duration of T2D with HbA1c was associated with executive functioning (p=.006), semantic categorization (p=.019), attention/working memory (p=.011), and overall cognition (p=.006), such that the associations between duration of T2D and cognitive impairment increased as HbA1c levels increased—but not for episodic memory (p=.984). Conclusions Since duration of T2D was associated with cognition in higher HbA1c levels and overall no associations were found in lower HbA1c levels, our results suggest that individuals with T2D may limit their risk of future cognitive decline by maintaining long-term good glycemic control.

Glucose level decline precedes dementia in elderly African Americans with diabetes

“…Reports from previous studies have suggested that midlife rather than late life diabetes is a risk factor for dementia and that longer duration is associated with greater risk [28, 29]. Unfortunately our electronic medical record system, which was unable to capture midlife data for all participants in our cohort, did not allow us to address this issue.…”

Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes

“…As associations of the Hp genotype with cardiovascular disease have been consistently stronger in type 2 diabetes [50, 51], it would not be surprising if associations of Hp with cognition were also greater in the type 2 diabetes population. The use of follow up years in the registry as a surrogate for duration of type 2 diabetes was a truncated estimate for all those who already had diabetes when entering the registry, thus the reported values may reflect an under estimate [34]. Another limitation was the use of only one subtest from the WASI, Similarities, as a proxy for IQ.…”

“…Three sets of covariates were used for analyses: demographic characteristics (age, years of education and sex), type 2 diabetes-related characteristics (number of follow up years in the registry, a surrogate for duration of disease [34] and whether medication for type 2 diabetes was taken [no medication, hypoglycaemic medication, and insulin or insulin + hypoglycaemic medication]) and cardiovascular risk factors (BMI, creatinine, total cholesterol, triacylglycerols, and diastolic and systolic BP). The cardiovascular risk factors were calculated as the means of all assessments for each participant in the MHS diabetes registry.…”

The Israel Diabetes and Cognitive Decline (IDCD) study: Design and baseline characteristics

“…Finally, in the light of relationships of insulin [15], glycemic control [16], hypertension [12], and other diabetes-related characteristics with dementia risk in non-T2D individuals, discoveries from the IDCD study may not only be pertinent to T2D per se, but may generalize to all elderly. The overall hypotheses of the IDCD study are that glycemic control is a key factor and that not only it will be associated with cognitive decline, it will also modulate relationships of several other risk factors (such as the duration of disease [17] and inflammation [18]) with cognition, such that relationships will be stronger with poorer levels of glycemic control. Because T2D is associated with both neurodegenerative and vascular brain abnormalities [19], we hypothesize that both episodic memory (affected early in the course of AD) and executive functions and working memory (affected by cerebrovascular disease) will be associated with the risk factors.…”