Article

The spectrum of nonmotor symptoms in early Parkinson disease

and Cambridge Centre for Brain Repair (R.A.B.), Cambridge University, Cambridge, UK.
Neurology (Impact Factor: 8.29). 01/2013; 80(3):276-81. DOI: 10.1212/WNL.0b013e31827deb74
Source: PubMed

ABSTRACT

Nonmotor symptoms (NMS) are common in patients with established Parkinson disease (PD) but their frequency in early PD has not been extensively studied. Our aim was to determine the frequency of NMS in a cohort of patients with newly diagnosed PD.
A total of 159 patients with early PD and 99 healthy controls participated in this study. NMS were screened for using the Nonmotor Symptom Questionnaire. Other assessments included measures of motor disability (Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale [MDS-UPDRS]), disease severity (Hoehn & Yahr staging), depression (Geriatric Depression Scale), and global cognitive function (Mini-Mental State Examination and Montreal Cognitive Assessment).
The PD group reported a significantly greater number of NMS compared with controls (8.4 [4.3] vs 2.8 [2.6]). In the PD group, the most commonly experienced NMS were excessive saliva, forgetfulness, urinary urgency, hyposmia, and constipation. Patients with higher MDS-UPDRS III scores and those with the postural instability gait subtype experienced a greater number of NMS.
NMS are common in early PD and reflect the multisystem nature of the disorder. Even in the earliest stages of PD, NMS may be detrimental to patients' functional status and sense of well-being.

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    • "It is now well recognized that nonmotor symptoms are an integral part of the clinical spectrum of the disease [43] [44] [45] [46] and may even antedate the clinical manifestation of cardinal motor features of PD by several years in a substantial proportion of patients [7–9, 47] (Table 2). Considering Braak's hypothesis that PD pathology first starts in extranigral sites, particularly the olfactory system, lower brainstem and peripheral autonomic nervous system [4] [5] [48], it is intriguing to note that recent clinical studies have found certain nonmotor symptoms such as constipation , dream enacting behaviour, and smell-loss preceding the onset of first motor complaints into time periods that are longer before motor onset as compared to other nonmotor complaints [7] [9]. "
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    ABSTRACT: Parkinson's disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor symptom out of tremor, rigidity or postural instability. However, converging evidence from clinical, neuropathological, and imaging research suggests initiation of PD-specific pathology prior to appearance of these classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in relation to the development of disease-modifying or neuroprotective therapies which would require intervention at the earliest stages of disease. A key challenge in PD research, therefore, is to identify and validate markers for the preclinical and prodromal stages of the illness. Currently, several nonmotor symptoms have been associated with an increased risk to develop PD in otherwise healthy individuals and ongoing research is aimed at validating a variety of candidate PD biomarkers based on imaging, genetic, proteomic, or metabolomic signatures, supplemented by work on tissue markers accessible to minimally invasive biopsies. The definition of diagnostic criteria for prodromal PD will have to include combinations of markers which could define target populations and influence outcomes of future disease modification trials.
    Full-text · Article · Oct 2015
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    • "of Cognitive Impairment in Cohorts with Longitudinal Evaluation—Parkinson's disease) conducted between June 2009 and December 2011 [29] "
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    ABSTRACT: Measurement of gait is becoming important as a tool to identify disease and disease progression, yet to date its application is limited largely to specialist centres. Wearable devices enables gait to be measured in naturalistic environments however questions remain regarding validity. Previous research suggests that when compared with a laboratory reference, measurement accuracy is acceptable for mean but not variability or asymmetry gait characteristics. Some fundamental reasons for this have been presented (e.g. synchronisation, different sampling frequencies) but to date this has not been systematically examined. The aims of this study were to: (i) quantify a comprehensive range of gait characteristics measured using a single tri-axial accelerometer-based monitor, (ii) examine outcomes and monitor performance in measuring gait in older adults and those with Parkinson's disease (PD) and (iii) carry out a detailed comparison with those derived from an instrumented walkway to account for any discrepancies. Fourteen gait characteristics were quantified in 30 people with incident PD and 30 healthy age-matched controls. Of the 14 gait characteristics compared, agreement between instruments was excellent for 4 (ICCs 0.913 - 0.983); moderate for 4 (ICCs 0.508 - 0.766); and poor for 6 characteristics (ICCs -0.637 - 0.370). Further analysis revealed that differences reflect an increased sensitivity of accelerometry to detect motion, rather than measurement error. This is most likely because accelerometry measures gait as a continuous activity rather than discrete footfall events, per instrumented tools. The increased sensitivity shown for these characteristics will be of particular interest to researchers keen to interpret 'real world' gait data. In conclusion, use of a body worn monitor is recommended for the measurement of gait but is likely to yield more sensitive data for asymmetry and variability features.
    Full-text · Article · Apr 2015
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    • "However, the fact that NMS may arise as part of drug related effects and side effects confounds this issue further. Recently, the importance of measuring NMS using validated tools, such as the NMS Questionnaire (NMSQuest) [6] and the NMS Scale (NMSS) [7] has been described in two independent case control studies in drug na¨ıve PD [8] and early PD [9] patients. "
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    ABSTRACT: Background: Recent studies have demonstrated that, contrary to common perception non-motor symptoms (NMS) occur and may dominate early and untreated stage of Parkinson's disease (PD). Objective: The aim of this ongoing study was to describe the overall NMS profile and burden in drug naïve PD patients (DNPD) compared to a group of long-term PD patients (LTPD, disease duration ≥15 years). Methods: Cross sectional UK data from a multicenter (16 sites) collaboration were obtained and specifically NMS dataset from validated scales were analysed in DNPD and LTPD patients. The NMS scale (NMSS) was used as the primary outcome variable. Results: Out of a current database of 468 PD patients, 57 were DNPD (58% males, mean age 64.8 years, median Hoen and Yahr stage 1) and 25 were LTPD (44%, mean age 67.6 years, median Hoen and Yahr stage 3). DNPD patients had a significantly lower (p = 0.001) NMSS score (mean 45.5, range 1-150) compared to the LTPD patients (mean 74.0, range 6-155), but 26.3% had severe and 19.3% had very severe burden of NMSS using NMSS cutoff scores. In comparison, 20.0% of the LTPD patients had severe and 60.0% very severe burden of NMS (p = 0.003). Conclusions: NMS are common in DNPD patients and over 45% may have severe to very severe burden of NMS, which is a key determinant of quality of life. In LTPD patients not only the burden of "very severe" NMS is significantly higher, but there are also differences in the profile of expression of NMS.
    Full-text · Article · Jun 2014 · Journal of Parkinson's Disease
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