Diagnosis and the premotor phase of Parkinson disease

Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurosciències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Hospital Clínic de Barcelona, Barcelona 08036, Spain.
Neurology (Impact Factor: 8.29). 03/2009; 72(7 Suppl):S12-20. DOI: 10.1212/WNL.0b013e318198db11
Source: PubMed


Clinical, neuroimaging, and pathologic studies have provided data suggesting that a variety of nonmotor symptoms can precede the classic motor features of Parkinson disease (PD) by years and, perhaps, even decades. The period when these symptoms arise can be referred to as the "premotor phase" of the disease. Here, we review the evidence supporting the occurrence of olfactory dysfunction, dysautonomia, and mood and sleep disorders, in this premotor phase of PD. These symptoms are well known in established PD and when presenting early, in the premotor phase, should be potentially considered as an integral part of the disease process. Even though information on the premotor phase of PD is rapidly accumulating, the diagnosis of premotor PD remains elusive at this time. Should a safe and effective treatment with disease-modifying or neuroprotective potential in PD become available, identifying individuals in the premotor phase will become a serious priority.

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    • "These symptoms occur both early and throughout the entire disease course and have a strong impact on the quality of life. In particular, depression is an important nonmotor symptom, present in up to two-thirds of all PD patients (Tolosa et al. 2009; Gallagher et al. 2010; Hinnell et al. 2012). Moreover, large-scale epidemiological studies observed cognitive impairments in up to 20% of PD patients at disease onset (Aarsland et al. 2009); in advanced stages, more than 80% of patients may develop dementia (Hely et al. 2008). "
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    ABSTRACT: Adult neurogenesis is limited to specific brain regions in the mammalian brain, such as the hippocampal dentate gyrus and the subventricular zone/olfactory bulb system. Alterations in adult neurogenesis appear to be a common hallmark in different neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). This is remarkable, because the distinct pathological proteins responsible for the different diseases induce the loss of different neural populations. Impaired adult neurogenesis was shown in numerous animal models of neurodegenerative diseases; however, only few post-mortem studies have been performed. We will review concepts related to the interplay between cellular plasticity in regions of adult neurogenesis with a specific focus on cell-autonomous and non-cell-autonomous factors. Furthermore, various strategies aimed to stimulate neuronal plasticity will be discussed within the context of a potential translation into therapeutic approaches for neuropsychiatric symptoms associated with PD, HD, and AD. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor perspectives in biology 04/2015; 7(4):a021287. DOI:10.1101/cshperspect.a021287 · 8.68 Impact Factor
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    • "Thus, disease-modifying therapies should be much more promising when instated in early premotor stages of PD. To this end, PD risk scores have been introduced [30, 31]. Stages 5 and 6, finally, are characterized by the involvement of the basal forebrain and cortical regions, including the entorhinal cortex and the cornu ammonis regions of the hippocampus. "
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    ABSTRACT: In Parkinson's disease (PD) and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.
    Neural Plasticity 07/2014; 2014:454696. DOI:10.1155/2014/454696 · 3.60 Impact Factor
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    • "Little is known about the progression and the natural history regarding the large range of NMS that complicate the journey of a patient with PD. The NMS are recognized to be present from the " pre-motor " stage [3] to the final palliative stage of PD [4]. Interestingly , while motor progression in PD appears to follow a largely linear pattern, NMS are more complicated and while few remain static, other may improve and some may worsen [5]. "
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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.
    Journal of Parkinson's Disease 06/2014; 4(3). DOI:10.3233/JPD-140372 · 1.91 Impact Factor
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