Diabetes is associated with dementia risk. We recently reported incident glucose disorders predicted accelerated cognitive decline.1 Insulin deficiency may contribute: low insulin levels are associated with greater cognitive decline. In contrast, insulin appears have positive neurotropic effects on the brain and be involved in regulating learning circuitry. Associations of low insulin levels on incident dementia and brain volume are unclear.
We hypothesized that lower insulin levels contribute to dementia risk. We examined whether greater ∆cognition, ∆brain volume and incident dementia at 4y were predicted by “low insulin” estimated by lowest baseline insulin tertile, ∆insulin, or incident diabetes.
Cognition was measured by neuropsychological testing1 at baseline, 2y and 4y in 682 participants free of diabetes at baseline; serum fasting insulin and total brain volume (TBV, by MR in n=259) measured at 0 and 2y. Covariates: age sex, education, hypertension history, smoking, blood pressure and apoEe4 genotype.
Baseline mean±SD age was 78.2±4.6y, FGL 5.6±0.6mmol/L and insulin 14.7±5.9uU/mL. There were 40 incident dementia cases at 4y.
The decline in global cognition in the low vs. higher baseline insulin tertile (-0.20 ± 0.05 v -0.26 ± 0.04, p=0.15). ∆TBV was similar between low and high insulin tertiles (-27.1 ±3.9 v -31.7 ±4.6 cm3, p=0.39).
Changes in cognition and TBV were similar in analyses restricted to subjects with FGL≤5.5mmol/L.
Incident dementia was associated with a trend for lower baseline insulin (13.3±0.9 v 14.6±0.3 uU/mL, p=0.07). Logistic regression analyses found incident dementia was independently predicted by incident diabetes (OR 16.4, 95%CI 2.1-127.2, p=0.007), apoEe4 genotype (p=0.007) and age (p=0.04), but not baseline insulin or ∆insulin.
Incident diabetes is a strong predictor of incident dementia in the elderly. Low insulin levels did not predict adverse brain tissue loss, cognitive decline or incident dementia. Prior observations that insulin may protect brain health in the elderly may not have adequately adjusted for detrimental effects of rising glucose on the brain.