Insulin resistance increases the risk of conversion to the Subcortical Small Vessel Type of Dementia

BackgroundInsulin resistance (IR) has been linked to cognitive impairment and white matter hyperintensities on magnetic resonance imaging in population-based studies. However, in the clinical setting, the impact of IR on the risk of the subcortical small vessel type of dementia (SSVD) is unknown.ObjectiveTo investigate whether levels of the homeostatic model assessment of insulin resistance (HOMA-IR) were associated with the risk of SSVD or Alzheimer's disease (AD) in a memory clinic cohort.MethodsWe included 352 patients with subjective or objective mild cognitive impairment (SCI or MCI) at baseline. Cox regression, adjusted for covariates, was used to assess the associations between baseline HOMA-IR and the risk of incident SSVD or AD.ResultsDuring follow-up (mean 4.1 years), 83 (24%) patients converted to dementia (SSVD, n = 28; AD, n = 55). Baseline HOMA-IR (per standard deviation increase) was associated with increased risk of progression to SSVD (adjusted hazard ratio [HR] = 1.41, 95% CI: 1.16 – 1.73). Furthermore, patients in the highest HOMA-IR quintile (Q5) had an almost seven-fold increased risk of SSVD compared with those in the lowest quintile (Q5 vs. Q1; adjusted HR = 6.87, 95% CI: 1.09 - 43.38). There was no association between HOMA-IR and the risk of AD.ConclusionIR is a strong predictor of the risk of SSVD, but not of the risk of AD, in patients with SCI or MCI. These findings suggest that IR participates in SSVD progression and that HOMA-IR is a potential tool for risk stratification.