Interleukin-1α, interleukin-1β and tumor necrosis factor-α genetic variants and risk of dementia in the very old: evidence from the "Monzino 80-plus" prospective study.

The association among single nucleotide polymorphisms in inflammatory genes as interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) and dementia has been explored mostly in Alzheimer's disease, while few data addressing their association with dementia in very old people are available. We performed a prospective, door-to-door population-based study of 80 years or older residents in eight municipalities of Varese province, Italy (the Monzino 80-plus study). No difference was found by a cross-sectional approach comparing IL-1α rs1800587, IL-1β rs3087258 and TNF-α rs1799724 genotypic and allelic frequencies between those affected and not affected by dementia. After a 5-year follow-up, the elderly carriers of T-allele of TNF-α rs1799724 were at an increased risk of dementia (p = 0.03). This association was no more significant adjusting for the apolipoprotein E epsilon-4 allele (APOE-ε4, p = 0.26), which was an independent predictor of dementia onset (p = 0.0002). In short, in this Italian population of oldest olds, dementia was associated to the APOE-ε4 allele only.