Depression and Cognitive Impairment in Parkinson's Disease: A Role for Inflammation and Immunomodulation?

Abstract

The etiology of Parkinson's disease (PD) is complex and not fully understood, most probably because of the multiplicity of factors involved. Inflammatory and abnormal immune responses have been hypothesized to play a crucial role in PD. Not only in the brain, but also peripherally, inflammation is believed to contribute to the onset and progression of the neurodegenerative process seen in PD. Furthermore, increased inflammatory responses have been described both in the brain and peripheral blood of PD subjects. Although PD is considered a motor disorder, nonmotor symptoms are extremely frequent and disabling. Cognitive impairment and mood alterations are such symptoms that deserve increased attention since on the one hand they can appear even before typical motor disturbances are recognized, and on the other hand they are associated with high morbidity and mortality. A growing body of evidence suggests the existence of a link between inflammatory-immune responses and the occurrence of depression and cognitive impairment in PD patients. However, not all data are equally conclusive and are sometimes even conflicting. The aim of this brief review is to give an overview of the possible role that inflammation and immunomodulation may play in PD together with their putative impact on mood and cognitive alterations. What clearly emerges from this work is the fact that studies performed until now lack standardized and comparable methods to analyze both clinical and biological parameters. It is thus difficult to conclusively link mood and cognitive changes to underlying pathological mechanisms. Additional studies in this direction are warranted to convincingly establish or refute any causative relation.

Causes of Death Associated With Prolonged TV Viewing

“…For example, TV viewing has been associated with a prothombotic/inflammatory state (i.e., interleukin 6, C-reactive protein, and endothelial function) 12,33,34 which, in turn, has been linked with progression of COPD, 35 Parkinson disease, 36 and sepsis mortality, 29 perhaps due to inactivity associated with prolonged TV viewing. Similarly, TV viewing has been associated with lower cardiorespiratory fitness 24 and muscle strength.…”

Peripheral Administration of the Selective Inhibitor of Soluble Tumor Necrosis Factor (TNF) XPro®1595 Attenuates Nigral Cell Loss and Glial Activation in 6-OHDA Hemiparkinsonian Rats

“…The significance of being able to block inflammation at any point during the disease might have benefits for non-motor symptoms [13, 39]. Subsequently, others have shown that TNF [16] and c-reactive protein (CRP), classic companion biomarkers of inflammation, were correlated with fatigue [15], depression [40], cognition [41], and hallucination [42] in PD patients and plasma solTNF receptors were correlated with cognitive impairment in PD patients [17].…”

Immune system responses in Parkinson's disease: Early and dynamic

“…A recent meta‐analysis reports that pro‐inflammatory cytokines such as IL‐1b, IL‐6, and TNF, but also others such as IL‐10 (known for its anti‐inflammatory actions) and RANTES (known for its chemotactic properties) are increased in PD, suggesting a complex ongoing regulation of the immune response (Qin, Zhang, Cao, Loh, & Cheng, ). Interestingly, these soluble markers were correlated with non‐motor symptoms, which are proposed to precede motor symptomatology (Kohler, Krogh, Mors, & Benros, ; Pessoa Rocha, Reis, Vanden Berghe, & Cirillo, ). In particular, depression in PD patients has been associated with increase of several cytokines, although there is no clean consensus of which factors are up or down in PD patients relative to healthy controls.…”