Insulin resistance increases the risk of conversion to the subcortical small vessel type of dementia.

BACKGROUND: Insulin resistance (IR) has been associated with cognitive impairment and white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) 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. OBJECTIVE: To investigate whether the homeostatic model assessment of insulin resistance (HOMA-IR) was associated with the risk of SSVD or Alzheimer's disease (AD) in a memory clinic cohort. METHODS: We included 352 patients from the Gothenburg MCI study with subjective or mild cognitive impairment (SCI or MCI) at baseline. SSVD was diagnosed based on clinical symptomatology, including predominant frontal lobe symptoms, and WMH amount on MRI. Cox regression, adjusted for covariates, assessed the associations between baseline HOMA-IR and incident SSVD or AD. RESULTS: During follow-up (mean 4.1 years), 83 (24%) patients developed dementia (SSVD, n = 28; AD, n = 55). Baseline HOMA-IR (per standard deviation increase) was associated with increased risk of SSVD (adjusted hazard ratio [HR] = 1.41, 95% CI: 1.16-1.73). Patients in the highest HOMA-IR quintile had an almost seven-fold higher risk of SSVD than those in the lowest quintile (adjusted HR = 6.87, 95% CI: 1.09-43.38). These associations remained significant also after excluding patients with diabetes. HOMA-IR was not associated with AD. CONCLUSION: IR is a strong predictor of SSVD, but not AD, in patients with SCI or MCI. This suggests that IR contributes to SSVD progression and that HOMA-IR may be a useful tool for risk stratification.