Academic journal article Environmental Health Perspectives

Research on the Premotor Symptoms of Parkinson's Disease: Clinical and Etiological Implications

Academic journal article Environmental Health Perspectives

Research on the Premotor Symptoms of Parkinson's Disease: Clinical and Etiological Implications

Article excerpt

Introduction

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and severely affects quality of life. More than 1 million older U.S. adults live with PD, and the number will double by the year 2030 (Bach et al. 2011). Clinical diagnosis of PD is currently based on the presence of motor dysfunction including rest tremor, bradykinesia, and rigidity. PD patients also suffer from a wide range of non-motor symptoms--including hyposmia (poor sense of smell), gastroi ntestinal dysfunction, psychiatric features (e.g., depression, anxiety, psychosis), sleep disorders, and mild-to-severe cognitive impairment--many of which are disabling and can be difficult to treat (Coelho and Ferreira 2012; Fernandez 2012) and greatly jeopardize the quality of life of PD patients (Storch et al. 2013). Pathologically, PD has been characterized by the loss of dopamine neurons in the substantia nigra pars compacta, which underlies motor dysfunction, and by the presence of Lewy bodies in selected regions of the brain.

The cardinal motor signs of PD become clinically evident when approximately 50% of the dopaminergic neurons in the substantia nigra are lost (Fearnley and Lees 1991). Despite symptomatic therapies for dopamine deficiency-related motor features, the disease continues to progress and often leads to severe mental and physical disabilities (Coelho and Ferreira 2012; Shulman et al. 2008) and increased mortality (Chen et al. 2006; Willis et al. 2012). To date, none of the available treatments can halt or reverse the pathological and clinical progression of PD, and novel strategies are needed. Research on disease-modifying strategies would be greatly assisted by the identification of high-risk populations. Recent interest has focused on the nonmotor symptoms of PD, some of which may predate motor signs and clinical diagnosis by years ("premotor symptoms" of PD). Accumulating epidemiol ogical and clinical evidence suggests that hyposmia (Ross et al. 2008), constipation (Abbott et al. 2007; Gao X et al. 2011; Savica et al. 2009), depression (Bower et al. 2010; Fang et al. 2010; Ishihara Paul et al. 2008; Shiba et al. 2000), anxiety (Bower et al. 2010; Ishihara-Paul et al. 2008; Shiba et al. 2000; Weisskopf et al. 2003), rapid eye movement sleep behavior disorder (RBD) (Claassen et al. 2010; Iranzo et al. 2006; Postuma et al. 2009; Schenck et al. 1996), excessive daytime sleepiness (EDS) (Abbott et al. 2005; Gao J et al. 2011), and autonomic dysfunction (Goldstein 2010) may occur well before the appearance of the classic motor dysfunction of PD. Evidence comes primarily from large prospective population-based cohort studies that were initially established for research on cancer and cardiovascular disease, such as the Honolulu Asia Aging Study (HAAS) (Ross et al. 2008) and the Health Professionals Follow-up Study (Gao X et al. 2011), and from retrospective examinations of archived medical records of PD cases and controls such as the Rochester Epidemiology Project (Savica et al. 2009). These findings are summarized in Table 1. A recent meta-analysis also confirmed that constipation and mood disorders were associated with higher risk of PD (Noyce et al. 2012). Hyposmia, RBD, and EDS were not included in this meta-analysis because risk estimates either were not available or were available from only one study.

The hypothesis that premotor symptoms precede the motor signs of PD is broadly compatible with neuropathological findings reported by Braak et al. (2003). This work, although controversial (Burke et al. 2008), suggests that deposition of [alpha]-synuclein in the form of Lewy bodies and Lewy neurites develops in the PD brain in six sequential stages. O -Synuclein pathology begins in the dorsal motor nucleus of the vagus and glossopharyngeal nerves and the anterior olfactory nucleus in stage 1, extends to the locus ceruleus and caudal raphe nuclei in the pons (stage 2), then to the substantia nigra (stage 3), to the temporal mesocortex (stage 4), and finally to the neocortex (stages 5-6). …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.