Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson’s disease: clues to early diagnosis and effective treatment

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by movement dysfunction due to selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. Non-motor symptoms of PD (e.g., sensory dysfunction, sleep disturbance, constipation, neuropsychiatric symptoms) precede motor symptoms, appear at all stages, and impact the quality of life, but they frequently go unrecognized and remain untreated. Even when identified, traditional dopamine replacement therapies have little effect. We discuss here the pathology of two PD-associated non-motor symptoms: olfactory dysfunction and depression. Olfactory dysfunction is one of the earliest non-motor symptoms in PD and predates the onset of motor symptoms. It is accompanied by early deposition of Lewy pathology and neurotransmitter alterations. Because of the correlation between olfactory dysfunction and an increased risk of progression to PD, olfactory testing can potentially be a specific diagnostic marker of PD in the prodromal stage. Depression is a prevalent PD-associated symptom and is often associated with reduced quality of life. Although the pathophysiology of depression in PD is unclear, studies suggest a causal relationship with abnormal neurotransmission and abnormal adult neurogenesis. Here, we summarize recent progress in the pathology of the non-motor symptoms of PD, aiming to provide better guidance for its effective management.

Zishen pingchan granules combined with pramipexole in the improvement of depressive symptoms in Parkinson's disease: a prospective, multicenter, randomized, double-blind, controlled clinical study

“…The etiology of dPD is complicated. Some studies suggest that impaired monoaminergic neurotransmission contributes to dPD [15,16], and ZPG may suppress the over-activation of the c-Jun N-terminal protein kinase (JNK) pathway in the substantia nigra, alleviate the inflammatory response in nigral cells, protect the dopaminergic neuron and finally improve depression [17]. Besides, the regulation of dopamine receptors is considered as playing an important role in the pathogenesis of depression [18][19][20][21][22].…”

Changes in the Neuronal Architecture of the Hippocampus in a 6-Hydroxydopamine-Lesioned Rat Model of Parkinson Disease

“…The most prevalent nonmotor symptoms in PD are depression, anxiety, cognitive decline, pain, fatigue, insomnia, and autonomic dysfunction. Furthermore, approximately 40%–50% of PD patients are diagnosed with anxiety or depression [ 5 ]. Moreover, the nonmotor symptoms that are associated with the hippocampus significantly affect PD patients’ quality of life [ 6 ].…”

Associations of Sleep Disorders With Depressive Symptoms in Early and Prodromal Parkinson’s Disease

“…Non-motor symptoms in the early/prodromal stages of PD act as useful biomarkers for predicting the onset of motor symptoms and diagnosing PD, and identifying patients at risk of developing other complications (Bang et al, 2021).…”

“…Damaged noradrenergic function in PD was also associated with RBD (Sommerauer et al, 2018;Pilotto et al, 2019). Taken together, depression in PD may be attributed to the disruption of neurotransmitter systems, such as dopamine (SN), serotonin (raphe nuclei), and noradrenaline (locus coeruleus) (Maillet et al, 2016;Jin et al, 2017;Hustad and Aasly, 2020;Park et al, 2020;Bang et al, 2021).…”