Objective: To examine cognitive correlates associated with FOG that persists in both the ON and OFF medication states (ONOFF-FOG) vs. FOG that appears only in the OFF state (OFF-FOG), or that is absent (NO-FOG).

Background: We have previously shown that freezing of gait (FOG) subtypes based on levodopa responsiveness (patient self-report) have different cognitive correlates in Parkinson’s disease (PD).[1] We recently used a comprehensive levodopa challenge paradigm[2] to demonstrate that in some patients, FOG persists in the presence of peak dopaminergic therapy, even while other parkinsonian symptoms respond appropriately.

Method: PD patients were enrolled and assessed for FOG status with a comprehensive levodopa challenge paradigm.[2] Cognitive testing was assessed on a separate testing day. We performed univariate ANOVAs comparing scores of each outcome measure across FOG groups. Outcome measures that yielded significant initial F-tests after correction for multiple comparisons with a Holm procedure were then analyzed with multivariate models.

Results: N = 45 exhibited a full “ON” state plus a clinically-meaningful response to the levodopa challenge (≥20% decrease in MDS-UPDRS-III), and were included in subsequent analyses. Several outcomes yielded statistically-significant (HVLT[3] Total Recall, HVLT Delayed Recall) or marginally-significant (Digit Span Backward, MoCA) initial univariate F-tests. However, the only outcome measure that survived initial F-test after false positive control with a Holm procedure was the total score on the HVLT (P < 0.01, uncorrected, P = 0.02, corrected). HVLT Total Recall was analyzed with a multivariate model that controlled for age, sex, and PD duration. This model revealed a significant contrast between ONOFF-FOG and OFF-FOG (P = 0.02) after controlling for covariates, but no significant difference between OFF-FOG and NO-FOG (P = 0.37).

Conclusion: These results suggest that ONOFF-FOG may be uniquely associated with memory impairments as measured by the HVLT total score. More research is required to understand how neural substrates of memory could potentially contribute to FOG.

References: [1] Factor, S. et al. Freezing of gait subtypes have different cognitive correlates in Parkinson’s disease. Parkinsonism & Related Disorders 20, 1359–1364 (2014). [2] McKay, J. L. et al. Freezing of Gait can persist after an acute levodopa challenge in Parkinson’s disease. npj Parkinson’s Disease 5, 25 (2019). [3] Brandt, J. The Hopkins verbal learning test: Development of a new memory test with six equivalent forms. Clinical Neuropsychologist 5, 125–142 (1991).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/freezing-of-gait-that-persists-from-the-off-to-the-on-state-is-associated-with-memory-impairments-in-parkinsons-disease/