Objective: To assess if presence of cognitive side effects during an initial levodopa trial suggests the ultimate diagnosis of atypical Parkinson (APD) vs Parkinson disease (PD)

Background: Distinguishing between PD and APD very early in the disease course can be challenging as many of the clinical “red flags” associated with APD can take years to emerge. Identification of new “red flags” that present within five years of symptom onset may allow for earlier diagnosis [1]. Anecdotally, clinicians have observed that patients with APD complain of cognitive side effects (i.e. foggy headedness, fatigue, light headedness) with early levodopa exposure. We therefore performed a retrospective chart review to assess if cognitive side effects were associated with eventual APD diagnosis.

Method: In this retrospective study, records were collected for patients seen at least once at the Mount Sinai Union Square Movement Disorders Clinic between 1/1/2014-8/5/2020. Inclusion criteria were: ICD code for PD, APD, MSA, CBD, PSP, or DLB, trial of carbidopa-levodopa, sufficient documentation of clinical response to trial, and availability of clinical assessment at least 5 years after symptom onset. Exclusion criteria included concomitant diagnosis of FTD or Alzheimer disease. Data collected included demographics, year of initial motor symptom onset, date of initial diagnosis, diagnosis after at least 5 years of motor symptoms (using criteria guidelines for each disease [2-6]), diagnosis certainty level [2-6], and levodopa trial details (including presence and type of side effect). Chi-square test was used to assess the difference between the proportion of patients with PD vs APD with cognitive side effects to levodopa.

Results: Of 1104 patients identified, 164 patients (89 with PD and 75 with APD) met review criteria. There were 64 patients with established PD and 25 with probable PD. There were 30 patients with DLB (30 probable), 18 with MSA (3 clinically established, 15 clinically probable), 4 with CBD (2 probable sporadic, 2 possible), and 23 with PSP (22 probable, 1 possible). There was a greater proportion of patients with APD than PD who reported cognitive side effects to levodopa (22.7% vs 7.9%, P=0.002).

Conclusion: Cognitive side effects to levodopa may occur at higher rates in patients with APD than PD. This could be a potential clinical clue to aid in the early identification of patients with an APD.

References: [1] Vasta R, Nicoletti A, Mostile G, et al. Side effects induced by the acute levodopa challenge in Parkinson’s Disease and atypical parkinsonisms. PLoS One. 2017;12(2):e0172145. Published 2017 Feb 16. doi:10.1371/journal.pone.0172145
[2] Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591-1601. doi:10.1002/mds.26424
[3] Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32(6):853-864. doi:10.1002/mds.26987
[4] Armstrong MJ, Litvan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80(5):496-503. doi:10.1212/WNL.0b013e31827f0fd1
[5] Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022;37(6):1131-1148. doi:10.1002/mds.29005
[6] McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88-100. doi:10.1212/WNL.0000000000004058

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-side-effects-to-initial-levodopa-exposure-as-a-red-flag-a-retrospective-study/