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Neurodegenerative Disease Parkinson’s Disease Ergun Y Uc, MD,1


Non-motor Symptoms in Parkinson’s Disease Jon Tippin, MD,1


Kelvin L Chou, MD,2 Kevin C Doerschug, MD4 and Decontee M Jimmeh Fletcher, MD5


1. Associate Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City; 2. Clinical Associate Professor, Departments of Neurology and Neurosurgery, University of Michigan; 3. Assistant Professor, Department of Urology, University of Iowa; 4. Associate Professor, Department of Internal Medicine, University of Iowa; 5. Assistant Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City


Bradley A Erickson, MD,3


Abstract


In addition to typical motor dysfunction (parkinsonism), diverse non-motor symptoms (NMS) are frequently observed in patients with Parkinson’s disease (PD). Some NMS may antedate the diagnosis of PD. Examples of NMS include cognitive impairment, autonomic dysfunction, visual dysfunction, sleep abnormalities, and psychiatric disorders. NMS are associated with wide-ranging abnormalities in extranigral dopaminergic systems and non-dopaminergic (e.g. cholinergic, noradrenergic, serotoninergic) systems. The type and severity of NMS vary based on age, disease severity, and predominant motor symptoms. NMS can be disabling and reduce quality of life. Treatment of NMS can be challenging. Some NMS are helped by dopaminergic treatment, whereas others can be induced or exacerbated by treatments that help the motor dysfunction. Physicians should probe their PD patients about their NMS and address them for better care. Clinical trials should incorporate NMS as outcomes for more meaningful conclusions on the effect of treatments under investigation.


Keywords Parkinson’s disease, cognition, dementia, vision, constipation, autonomic dysfunction


Disclosure: The authors have no conflicts of interest to declare. Received: November 14, 2011 Accepted: December 23, 2011 Citation: US Neurology, 2011;7(2):113–9 Correspondence: Ergun Y Uc, MD, Department of Neurology, University of Iowa Carver College of Medicine, 200 Hawkins Drive-2RCP, Iowa City, IA 52242. E: ergun-uc@uiowa.edu


The degeneration of the dopaminergic nigrostriatal system and parkinsonism (rest tremor, rigidity, bradykinesia, and postural instability/gait disorder) represent only one aspect of Parkinson’s disease (PD), a multifaceted and complex disorder.1


In addition to this


typical motor dysfunction, non-motor symptoms (NMS) also significantly reduce of quality of life.2–4


Several non-motor features are associated


with deficits in extranigral dopaminergic pathways (e.g. mesolimbic, mesocortical), while others involve non-dopaminergic systems in the nervous system (e.g. cholinergic, noradrenergic, serotoninergic).5


Sleep


(e.g. rapid eye movement behavior disorder), olfactory, and autonomic dysfunction (e.g. constipation) may precede the onset of parkinsonism by many years,1,6


consistent with the debated notion that PD pathology starts in the lower brainstem and that midbrain (i.e. nigral) involvement represents stage three out of six pathologic stages.7


Considering


parkinsonism as just the tip of the iceberg of a multifaceted and complex disorder, PD might be better viewed as a ‘centrosympathomyenteric neuronopathy,’ as per Langston.1


In this article, various non-motor aspects


of PD (see Table 1) are discussed. Cognition


Cognitive impairment can be present in the early,8,9 even yet untreated10


stages of PD. Cognitive impairment is associated with poorer quality of life11 and reduced activities of daily living (e.g. worse driving12–15


),9 © TOUCH BRIEFINGS 2011 and increases


cost of care in PD.16


home placement and death.17,18


Dementia in PD is an important risk factor for nursing Depending on the baseline age, severity of


parkinsonism, cognitive function, and setting (hospital versus community based) of the studied population, 20–83 % of PD patients develop dementia.19–25


mild cognitive impairment (PD-MCI),26,27 approximately 20 % at time of diagnosis.28


About one-quarter of PD patients without dementia have which is shown to be present in The typical cognitive deficits


in PD include visuospatial, attentional, and executive deficits, but memory deficits are also present.29


Cognitive impairment in PD is associated with


limbic and cortical Lewy bodies, amyloid plaques, and central cholinergic deficits in addition to dysfunction of dopaminergic frontostriatal circuits.29 Risk factors for dementia include postural instability and gait difficulty, bulbar dysfunction, hallucinations, advanced age, male gender, depression, autonomic dysfunction, and poor performance on baseline cognitive tests.20,21,30–32


PD-MCI predicts a shorter time to dementia.26


Dopaminergic medications have mixed effects on cognition. They can improve or impair cognitive performance depending on the nature of the task and the basal level of dopamine function in the underlying corticostriatal circuitry.33


For example, task switching (which is


dependent on circuitry connecting the dorsolateral prefrontal cortex and the posterior parietal cortex to the dorsal caudate nucleus) improved, but probabilistic reversal learning (which is dependent on orbitofrontal


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