The relationship between cognitive performance and insulin resistance in non-diabetic patients with mild cognitive impairment

Objective: Insulin resistance (IR) is a distinct and early feature of type 2 diabetes mellitus and metabolic syndrome. IR is thought to play a vital role in cognitive impairment. We conducted this study to understand the early characteristics of cognitive dysfunctions attributable to IR.

Methods: This study included 85 consecutive non-diabetic elderly participants with mild cognitive impairment (MCI). IR was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR). Cognitive performances were analyzed as a function of scores on the HOMA-IR.

Results: The group analysis those with and without IR did not show any differences in the cognitive performance although higher HOMA-IR was closely associated with lower performances in immediate recall on the Seoul Verbal Learning Test (SVLT-I) (r = -0.244, p = 0.026) and Controlled Oral Word Association Test (COWAT) (r = -0.270, p = 0.013). In subgroup analysis by APOE status, SVLT-delayed (p = 0.027) and COWAT (p = 0.016) scores were found to be significantly lower in the IR than the non-IR among those with APOE ε4 allele. In multiple regression analysis, impairment on the COWAT remained significantly correlated with scores on HOMA-IR (β = -0.271, t = -2.340, p = 0.022). However, IR status was identified to interact with APOE ε4 carriership toward poor performances in the COWAT (β = -0.335, t = -2.285, p = 0.026).

Conclusion: This study found a domain-specific impact of HOMA-IR scores on cognitive performances in non-diabetic patients with MCI. This association was profound only in APOE ε4carriers.