The Nonmotor Symptoms of Parkinson’s Disease: Update on Diagnosis and Treatment

Traditionally, treatment consists of reduction or elimination of dopamine agonists, though adjustment of levodopa therapy may also be necessary. Amantadine as an adjunct therapy has been shown in a randomized, double-blind crossover study to reduce impulsivity in a few patients with pathologic gambling [79].

Dopamine Dysregulation Syndrome

Dopamine dysregulation syndrome (DDS) is characterized by compulsive use of dopaminergic medications beyond what is needed to treat parkinsonian symptoms, and is associated with social impairment. Patients describe addictive symptoms like craving or intense desire to obtain more dopaminergic medication [9,74]. Like ICDs, treatment of DDS consists of modification to dopaminergic medications, though patients with DDS may also require psychiatric evaluation and treatment.

Punding

Punding is another compulsive disorder that is defined as an intense fascination with objects and is associated with repetitive handling, manipulation, sorting, or arrangement of the items [80]. Occurrence of punding has been associated with higher total daily levels of levodopa, although one study has also implicated dopamine agonists [15,81]. As with the other compulsive disorders, punding also tends to respond well to reduction or discontinuation of levodopa. Studies have demonstrated modest benefit with SSRIs or atypical antipsychotics in long-term follow-up [82,83], though one study reported worsening of punding with quetiapine [84].

Apathy

Epidemiology and Treatment

Apathy is often characterized by a loss of motivation or inability to initiate goal-directed behavior, which results in dependence on others for activities of daily living and increases caregiver burden [85]. Patients demonstrate indifference, lack of interest, or inability to express or describe emotion. The apathetic patient may lack spontaneous and voluntary activity, and their affect display is often flattened [86].

With a prevalence of 30% to 50% [87], apathy is as common as depression in PD patients [66,88]. Risk factors associated with apathy include advanced age, severity of depression, severity of motor dysfunction, and dementia [89]. Apathy is frequently mistaken for depression given the significant overlap in symptoms; however, the patient with pure apathy will deny sadness or depressed feelings. It is also important to distinguish apathy from motor impairment or cognitive dysfunction that could explain the behavioral changes. No medications have reliably been shown to improve apathy, though it may be improved with initiation of dopaminergic therapy, especially early in the course [86,90].

Sleep Disorders

The original report of PD by James Parkinson describes sleep disturbances and daytime somnolence [91], which suggests that sleep disorders may be an intrinsic feature of the neurodegenerative process of PD itself.

REM Behavioral Disorder

Epidemiology and Diagnosis

Rapid eye movement behavioral disorder (RBD) is a parasomnia characterized by vocalizations and motor activity during dreaming due to loss of normal atonia associated with rapid eye movement (REM) sleep. Patients enact their dreams, which may lead to violent behaviors that can injure the patient or their bed partner. RBD is seen in 25% to 50% of PD patients [92,93], with variability depending on diagnostic technique and patient selection. Polysomnography is the most important diagnostic tool and demonstrates increased chin tone and limb movements during REM sleep in RBD [94,95]. Diagnosis can also be made clinically with patient and bed partner reports, though sensitivity is only approximately 30% [15].