ObjectiveTo study the relationships of long-term trajectories of glycemic control with cognitive performance in cognitively normal elderly with type 2 diabetes (T2D).MethodsSubjects (n = 835) pertain to a diabetes registry (DR) established in 1998 with an average of 18 HbA1c measurements per subject, permitting identification of distinctive trajectory groups of HbA1c and examining their association with cognitive function in five domains: episodic memory, semantic categorization, attention/working memory, executive function, and overall cognition. Analyses of covariance compared cognitive function among the trajectory groups adjusting for sociodemographic, cardiovascular, diabetes-related covariates and depression.ResultsSubjects averaged 72.8 years of age. Six trajectories of HbA1c were identified, characterized by HbA1c level at entry into the DR (Higher/Lower), and trend over time (Stable/Decreasing/Increasing). Both groups with a trajectory of decreasing HbA1c levels had high HbA1c levels at entry into the DR (9.2%, 10.7%), and high, though decreasing, HbA1c levels over time. They had the worst cognitive performance, particularly in overall cognition (p<0.02) and semantic categorization (p<0.01), followed by that of subjects whose HbA1c at entry into the DR was relatively high (7.2%, 7.8%) and increased over time. Subjects with stable HbA1c over time had the lowest HbA1c levels at entry (6.0%, 6.8%) and performed best in cognitive tests.ConclusionGlycemic control trajectories, which better reflect chronicity of T2D than a single HbA1c measurement, predict cognitive performance. A trajectory of stable HbA1c levels over time is associated with better cognitive function.

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.

OBJECTIVEHaptoglobin (Hp) genotype (Hp 1-1, 1-2, or 2-2) is associated with risk for type 2 diabetes complications, but its relationship with cognitive compromise, a growing concern in type 2 diabetes, has rarely been studied. This study investigated whether Hp genotype is associated with cognitive function in cognitively normal elderly diabetic subjects.RESEARCH DESIGN AND METHODSRelationships of Hp genotype with episodic memory, semantic categorization, attention/working memory and executive function, and an overall cognitive score were examined in subjects from the Israel Diabetes and Cognitive Decline (IDCD) study.RESULTSIn the present analysis, 812 subjects participated (84 with Hp 1-1, 335 with Hp 1-2, and 393 with Hp 2-2 genotypes). Average was 72.9 years of age (SD 4.7), and Mini-Mental State Exam (MMSE) was 28.0 (SD 1.8). Compared with subjects with Hp 1-2 genotype, Hp 1-1 subjects performed significantly worse in semantic categorization (F = 7.03; P = 0.008) and the overall cognitive score (F = 5.57; P = 0.02). A separate stepwise multiple regression analysis demonstrated that compared with subjects with Hp 2-2 genotype, Hp 1-1 subjects performed significantly worse in semantic categorization (F = 4.18; P = 0.04) and the overall cognitive score (F = 4.70; P = 0.03). The contribution of cardiovascular risk factors to cognition was significantly higher in subjects with Hp 1-1 genotype compared with Hp 2 carriers (Hp 1-2 and Hp 2-2) in the semantic categorization (P = 0.009) and attention/working memory (P = 0.002) cognitive domains.CONCLUSIONSCompared with Hp 2 carriers, those with Hp 1-1 genotype present lower cognitive performance. Stronger relationships between cardiovascular risk factors and cognition in the latter group may suggest an underlying vascular mechanism.

Caffeine intake may have a beneficial role in cognitive functioning of elderly adults with T2D, which may be moderated by age. Greater GM volume may be a mechanism underlying the association of higher caffeine intake with better cognitive function.