Abstract
BACKGROUND: Freezing of gait (FOG), is associated with impairment of different cognitive functions. Previous studies hypothesized that FOG may be due to a loss of automaticity. RESEARCH QUESTION: To explore whether FOG is associated with impairment in cognitive functions, focusing on retrograde procedural memory, the memory responsible for the automatic, implicit stored procedures that have been acquired in earlier life stages. METHODS: In this cross-sectional, case-control study, 288 people with typical Parkinson's disease (PD) from the Luxembourg Parkinson's Study were assigned to Freezers (FOG(+)) and non-Freezers (FOG(-)) based on the MDS-UPDRS 2.13 (self-reported FOG episodes) and 3.11 (FOG evaluated by clinicians during gait assessment). Both groups were matched on age, sex and disease duration. Global cognition (MoCA), retrograde procedural memory and visuo-constructive abilities (CUPRO), psychomotor speed and mental flexibility (TMT) were assessed. Furthermore, we repeated our analyses by additionally controlling for depression (BDI-I). RESULTS: Besides lower global cognition (MoCA; p = 0.007) and mental flexibility (TMT-B and Delta-TMT; p < 0.001), FOG(+) showed a lower performance in retrograde procedural memory (CUPRO-IS1; p < 0.001) compared to FOG(-). After controlling additionally for depression, our main outcome variable CUPRO-IS1 remained significantly lower in FOG(+) (p = 0.010). CONCLUSION: Our findings demonstrated that besides lower global cognition and mental flexibility scores, FOG(+) showed lower performance in retrograde procedural memory compared to matched FOG-control patients, even when accounting for factors such as age, sex, disease duration or depression. SIGNIFICANCE: In the context of limited treatment options, especially for non-invasive therapeutic approaches, these insights on procedural memory and FOG may lead to new hypotheses on FOG etiology and consequently the development of new treatment options.