Haptoglobin 1-1 Genotype Is Associated With Poorer Cognitive Functioning in the Elderly With Type 2 Diabetes

Abstract

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.

P3‐250: Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes

“…The MMSE mean score was 28.0 (SD = 1.8), which is consistent with normal cognition. The Hp 1-1 carriers and non-carriers did not differ in any of the characteristics except for the MMSE (p = 0.02), with lower scores in Hp 1-1 carriers, which is consistent with our previous findings [17]. There were significant associations of HbA 1c with cognition for executive function (p < 0.001) and overall cognition (p = 0.003), which is also consistent with previous findings from this sample [40].…”

“…We also noted that the collective association of seven cardiovascular risk factors with cognition was significantly stronger among Hp 1-1 carriers [17]. HbA 1c , the gold standard indicator of glycaemic control and a consistent predictor of type 2 diabetes micro-and macrovascular complications and of ischaemic stroke [18], has been associated with cognitive dysfunction and decline among cognitively normal elderly with [5] and without type 2 diabetes [19].…”

“…We recently published that elderly patients with type 2 diabetes carrying the Hp 1-1 genotype have poorer cognitive function than both Hp 1-2 and Hp 2-2 carriers (who have similar cognitive function) [17]. We also noted that the collective association of seven cardiovascular risk factors with cognition was significantly stronger among Hp 1-1 carriers [17].…”

“…The IDCD study design has been previously described in detail [17]. Briefly, the IDCD recruited community-dwelling elderly with type 2 diabetes (65+ years old) living in central Israel, from approximately 11,000 clients enrolled in the diabetes registry of the Maccabi Healthcare Services (MHS).…”

“…With the exception of demographic characteristics and depressive symptoms, measured at baseline of the IDCD, all covariates were retrieved from the MHS diabetes registry. All these covariates are potential confounders that have been associated with cognitive function [17,36], and thus may account for some of the variance in cognition.…”