Insulin resistance is associated with poorer verbal fluency performance in women

Abstract

Aims/hypothesis Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association. Methods The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA-IR was used to measure insulin resistance. Cognitive function was tested by word-list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests. Results Higher HOMA-IR was associated with poorer verbal fluency in women (p<0.0001) but not in men (p=0.56).Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p=0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p=0.02). Conclusions/interpretation To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women.

Changes in metabolic risk factors over 10 years and their associations with late‐life cognitive performance: The Multi‐Ethnic Study of Atherosclerosis

“…However, baseline diabetes, hypertension, age and carriage of the APOE ε4 allele significantly modified associations between CASI and the metabolic factors. These findings suggest that metabolic risk factors for dementia may have greater effects on cognition among those with chronic metabolic diseases and among APOE ε4− individuals, which is consistent with our previous findings in trials of intranasal insulin [24], [25] and other large cohort studies [19], [26].…”

“…The results presented herein show that elevated metabolic factors and not their changes over the mid-to-late-life transition period are predictors of cognitive performance in older adults. These findings add to a growing literature relating insulin resistance and prediabetes with poorer cognitive performance in both middle-age [17], [18] and late-life [8], [9], [19], especially in those at high risk for cardiovascular disease [20]. Other studies have reported that trajectories of insulin and HbA1c are associated lower cognitive performance [21].…”

[P4–134]: Insulin Resistance Is Associated With Reductions in Specific Cognitive Domains and Increases in CSF Tau in Cognitively Normal Adults

“…A weaker association was observed between HOMA-B and executive function and global cognition. Our findings are in agreement with previous studies showing similar associations of cognitive functioning with HOMA-IR in cognitively normal individuals from community-based volunteer 35 , population based 36 or family based 37 studies. Episodic memory is one of the earliest cognitive domains that show changes in the pre-clinical stages of AD.…”

The immune-opioid axis in prediabetes: prediction of prediabetes with insulin resistance by plasma interleukin-10 and Endomorphin-2 to kappa-opioid receptors ratio

“…Elevated IR is associated with increased risk of cognitive decline, including impaired verbal fluency and slow simple reaction time [16]. Therefore, the relationship between IR roles and the molecules that have a function in the brain duties in some insulin-related disorders, including prediabetes, remains to be elucidated.…”