Nonmotor symptoms and health‐related quality of life in early Parkinson's disease

At present, it is widely recognized that Parkinson’s disease (PD) is a complex clinical condition combining motor and nonmotor manifestations. From the pathologic point of view, PD is a multisystem disorder with lesions affecting not only the dopaminergic nigrostriatal system but also the mesocortical dopaminergic system, the noradrenergic locus coeruleus, serotonergic dorsal raphe nuclei, and cholinergic nucleus basalis of Meynert, as well as histaminergic, peptidergic, and olfactory-related limbic systems. These widespread alterations explain why the clinical manifestations of PD surpass the classic motor disorder to include neuropsychiatric, autonomic, sensorial, and sleep disorders. The availability of comprehensive instruments for the assessment of nonmotor symptoms (NMS) in PD has allowed estimations of the burden attributable to the nonmotor manifestations that are present in this condition. Studies have reported averages of 8 to 13 NMS per patient, and some patients report experiencing 30 or even 32 of these symptoms simultaneously, whereas only a small proportion of patients ( 2.5%) are completely free of NMS. These figures look unexpectedly high, but a considerable proportion of NMS are neither recognized by doctors nor spontaneously mentioned by patients and, subsequently, remain unnoticed at least until they are systematically investigated. In PD. the number and severity of NMS increase as the disease progresses, although the correlation between NMS prevalence or severity and PD progression (considering duration, Hoehn and Yahr stage, or motor impairment severity) is moderate as a whole. NMS are present in the “premotor phase” and are the dominant problems over the long-term, thus representing an outstanding component of the disease. In this issue, Duncan et al. report the results from a study focused on the influence of NMS on the healthrelated quality of life (HRQoL) of patients with newly diagnosed PD and compare their findings with those from healthy control participants. Eighty percent of their patients had Hoehn and Yahr stage 1 and 2 disease, and the mean levodopa equivalent daily dose was relatively low (just over 175 mg) in those who received treatment (87.3%). Using a nonmotor symptoms questionnaire (NMSQuest), the authors reported a mean of 8.3 NMS in the PD group (2.8 in the control group), a number near the 5 NMS average in untreated PD patients reported by Erro et al. In the cohort studied by Duncan et al., the most prevalent NMS in PD patients were hypersalivation and drooling, urinary urgency, hyposmia, anxiety, and constipation, and of all these symptoms were significantly more frequent in the PD group than in the control group. Memory problems and sleep disorders also were prevalent, but the difference between the control group and the PD group was not significant. Interestingly, patients who had the postural instability and gait difficulty (PIGD) PD subtype reported significantly more NMS than patients who had other subtypes. As measured by the disease-specific 39-item Parkinson’s Disease Questionnaire (PDQ-39), patients’ HRQoL was mildly affected (mean 5 18.1%, of a theoretical maximum of 100%), and the most affected domains were bodily discomfort, mobility, and activities of daily living. A significantly close correlation between HRQoL and NMS was observed for depression, anxiety, impaired concentration, memory complaints, and sleep disturbance. Most of these NMS are recognized determinants of HRQoL. Previous studies have determined the influence of NMS on the HRQoL of PD patients, but very few studies have focused on this correlation at early phases of the disease. All of these studies agree in their main findings: multiple NMS can be present simultaneously during the early clinical stages of the disease, and they significantly contribute to deterioration in the quality of life. -----------------------------------------------------------*Correspondence to: Dr. Pablo Martinez-Martin, Alzheimer Center Reina Sof ıa Foundation, C/: Valderrebollo, 5, 28031 Madrid, Spain; pmartinez@fundacioncien.es