Plasma Cytokine Levels in Relation to Neuropsychiatric Symptoms and Cognitive Dysfunction in Huntington's disease

In Huntington's disease (HD) the innate immune system is activated, as reflected by increased plasma levels of different cytokines.

To explore whether increased cytokine levels are associated with neuropsychiatric symptoms and cognitive dysfunction in HD mutation carriers.

Plasma cytokine levels of TNF-alpha, interleukin (IL)-1ra, IL-1β, IL-5, IL-6, IL-8 and Il-10 were assessed in 124 HD mutation carriers at two time points 2 years apart (totalling 214 observations). Using multilevel regression analysis, cytokines were analysed in relation to neuropsychiatric symptoms and cognitive dysfunction. Depressed mood was assessed with the depression subscale of the Problem Behaviours Assessment (PBA), apathy with the Apathy Scale, and irritability with the Irritability Scale. Cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and a battery of executive cognitive functioning tests, aggregated into an executive cognitive functioning (ExCog) score.

Inverse associations were found in adjusted models between IL-6 and ExCog score (β= -0.114; p = 0.01) and between IL-1ra and ExCog score (β= -0.110; p = 0.02). No associations between cytokine levels and any of the other neuropsychiatric symptom scores remained statistically significant in adjusted models.

Higher plasma levels of IL-6 and IL-1ra are weakly associated with cognitive dysfunction in HD, but not with other neuropsychiatric symptoms.