Relationship between circulating CD4+ T lymphocytes and cognitive impairment in patients with Parkinson's disease.

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons. Neuroinflammation may represent an important factor in the pathophysiology of PD and recent findings indicate that PD patients present a pro-inflammatory peripheral profile of CD4+ T lymphocytes, which may correlate with motor disability. However, no data are currently available on the relationship between CD4+ T lymphocytes and cognitive function in PD. The aim of our study is to evaluate the relationship between cognitive profile and circulating CD4+ T lymphocyte subsets in PD patients. PD patients underwent blood withdrawal and CD4+ T lymphocyte subpopulations, including CD4+ T naïve and memory cells, Th1, Th2, Th17, Th1/17 and T regulatory (Treg) cells were evaluated by flow cytometry. Cognitive evaluation was performed using Addenbrooke Cognitive Examination (ACE-R). 43 consecutive PD patients (31 males; age [mean ± SD]: 68.9 ± 8.4 years) were enrolled. 14/43 (32.6%) were drug naïve. Based on the ACE-R score, patients were divided in two groups using defined cutoff values. In comparison to patients with normal cognitive profile, patients with cognitive impairment had a higher number of circulating lymphocytes. Moreover, drug naïve patients with a worse cognitive outcome had a lower number of resting Treg and higher number of activated Treg. Furthermore, we found a correlation between pro-inflammatory peripheral immune phenotype and worse cognitive outcome in the ACE-R total and sub-items scores. In our cohort of PD patients, cognitive impairment was associated with higher number of circulating lymphocytes, and - at least in drug naïve patients - with dysregulation of the Treg compartment. Further studies are needed to assess whether and to what extent peripheral immunity mechanistically contributes to cognitive decline in PD.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.