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Neal Hermanowicz,1 Maria Cristina Ospina,2 Yasar Torres-Yaghi,3 Sherrie Gould,4 Kelly Papesh,5 Jason A Rivera,6 Susan Miller,6 Sarah Jones,6 Kelli Musick,7 Damian May7 1Christus-St. Vincent Neurology Specialists, Santa Fe, NM, USA; 2Regional Parkinson Center, Phoenix, AZ, USA; 3MedStar Georgetown University Hospital, Washington, DC, USA; 4Scripps Clinic Movement Disorder Center, La Jolla, CA, USA; 5Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA; 6Parkinson and Movement Disorder Alliance (PMD Alliance), Tucson, AZ, USA; 7ACADIA Pharmaceuticals Inc, San Diego, CA, USACorrespondence: Neal Hermanowicz, Tel +1 (505) 913-3877, Email nshermano@icloud.comPurpose: As the COVID-19 pandemic resulted in social restrictions around the globe, this cross-sectional survey aimed to assess the impact of social isolation on self- or proxy-reported symptoms of Parkinson’s disease (PD) during the pandemic.Patients and Methods: The survey was distributed among 7109 subscribers of the Parkinson and Movement Disorders Alliance (PMD Alliance) News and Information list and was open only to people with PD (PwP) and care partners (CP, defined as main caregivers of PwP and serving as proxy respondents). No attempt was made to identify PwP and CP pairs. The survey was distributed online using Survey Monkey between 01/06/2021 and 02/27/2021. Respondents were grouped by level of social support from outside of their household during the pandemic (decreased or maintained [ie, the same as pre-pandemic or increased]).Results: Of 7109 invited participants, 718 responded to the survey (response rate 10.1%). PwP (self-reports) accounted for 70.6% of respondents and CP (proxy reports) for 29.4%. Decreased social support from outside of the household during the COVID-19 pandemic (58.5% of all responses) was significantly associated with increases in sadness/depression and anxiety, compared with maintained levels of social support (p < 0.0001 for both comparisons). It was also associated with increased burden of several non-motor (decline in memory, problem solving, or communication, p = 0.0009; new or worsening confusion, p < 0.0001; new or worsening delusions, p = 0.018) and motor PD symptoms.Conclusion: Decline in social support from outside of the household during the COVID-19 pandemic showed a statistically significant and negative association with the burden of mood and non-motor symptoms of PD. These results call for increased vigilance towards non-motor symptoms in PwP experiencing social isolation and highlight the need for stronger provider focus on encouraging PwP and their CPs to build and maintain social connections and engagements.Keywords: Parkinson’s disease, social isolation, anxiety, depression, non-motor symptoms, COVID-19

Yasar Torres-Yaghi, Amelia Carwin, Jacob Carolan, Steven Nakano, Fahd Amjad, Fernando Pagan Department of Neurology, National Parkinson’s Foundation Center for Excellence, Translational Neurotherapeutics Program, Movement Disorders Program, MedStar Georgetown University Hospital, Washington, DC, USACorrespondence: Yasar Torres-YaghiMedStar Georgetown University Hospital, Department of Neurology, National Parkinson’s Foundation Center for Excellence, Translational Neurotherapeutics Program, Movement Disorders Program, 3800 Reservoir Road, NW, Washington, DC, 20007, USATel +1 202-444-6087Fax +1 202-444-2186Email yasaryaghi@gmail.comAbstract: In addition to the classic motor symptoms of Parkinson’s disease (PD), people with PD frequently experience nonmotor symptoms that can include autonomic dysfunction and neuropsychiatric symptoms such as PD psychosis (PDP). Common patient characteristics, including older age, use of multiple medications, and arrhythmias, are associated with increased risk of corrected QT interval (QTc) prolongation, and treatments for PDP (antipsychotics, dementia medications) may further increase this risk. This review evaluates how medications used to treat PDP affect QTc interval from literature indexed in the PubMed and Embase databases. Although not indicated for the treatment of psychosis, dementia therapies such as donepezil, rivastigmine, memantine, and galantamine are often used with or without antipsychotics and have minimal effects on QTc interval. Among the antipsychotics, data suggesting clinically meaningful QTc interval prolongation are limited. However, many antipsychotics have other safety concerns. Aripiprazole, olanzapine, and risperidone negatively affect motor function and are not recommended for PDP. Quetiapine is often sedating, can exacerbate underlying neurogenic orthostatic hypotension, and may prolong the QTc interval. Pimavanserin was approved by the US Food and Drug Administration (FDA) in 2016 and remains the only FDA-approved medication available to treat hallucinations and delusions associated with PDP. However, pimavanserin can increase QTc interval by approximately 5– 8 ms. The potential for QTc prolongation should be considered in patients with symptomatic cardiac arrhythmias and those receiving QT-prolonging medications. In choosing a medication to treat PDP, expected efficacy must be balanced with potential safety concerns for individual patients.Keywords: QTc interval prolongation, antipsychotic agents, clozapine, quetiapine, pimavanserin