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

OBJECTIVE Haptoglobin (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 METHODS Relationships 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. RESULTS In 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. CONCLUSIONS Compared 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.