Objective: We evaluated whether changes in cholinergic function might be related to increased fall risk in PD patients with Freezing of Gait (FoG).

Background: FoG is a severe episodic gait disturbance in patients with Parkinson’s Disease (PD), associated with higher risk of falls. A PET study showed that PD patients with FoG display cholinergic deficits selectively driven by nucleus basalis of Meynert neocortical denervation (Bohnen et al., 2014). In humans, cholinergic activity can be also estimated with short latency afferent inhibition (SAI), a transcranial magnetic stimulation technique that assesses an inhibitory circuit in the sensorimotor cortex.  To date, only one study investigated if changes in SAI might be associated with FoG (Picillo et al., 2015) and it failed. On the other hand, we recently showed SAI impairment in PD patients and elderly at high risk of falls (Pelosin et al., 2016).

Method: 31 PD patients with FoG (14 women; mean age 73.06 ± 4.23 SD), enrolled in the V-Time study, participated in this sub-study. Patients were divided into two groups on the basis of falls number ((=2 (falls2) or ≥3 (falls3+) in the previous 6 months). Disease severity was assessed with the UPDRS and FoG with the New FoG questionnaire (NFOG-Q). Cholinergic activity was estimated by means of SAI. Global cognition was tested with the Montreal Cognitive Assessment.

Results: Twenty participants were included in the falls3+ group, whereas eleven participants were enrolled in the falls2 group. Groups were similar for age, gender and disease duration (p always > 0.05). Results showed that SAI was reduced (i.e., less cholinergic activity) in PD patients with FoG in the falls3+ than in those in falls2 group (p=0.02). Patients in falls3+ group showed higher UPDRS score (p=0.04), worse impact of FoG on daily life (NFOG-Q Part III; p=0.01), worse short-term memory performance (delayed recall test; p=0.03).

Conclusion: Patients with FoG and recurrent falls had a significant impairment of SAI, suggesting reduced central cholinergic activity. This neurophysiological pattern was associated with cognitive dysfunction, related to short-term memory. SAI abnormalities and presence of cognitive impairment strongly support the hypothesis of cholinergic dysfunction in increasing fall risk in PD patients with FoG.

References: Bohnen NI, Frey KA, Studenski S, Kotagal V, Koeppe RA, Constantine GM et al. Extra-nigral pathological condi- tions are common in Parkinson’s disease with freezing of gait: an in vivo positron emission tomography study. Mov Disord. 2014 29:1118–1124 Pelosin E, Ogliastro C, Lagravinese G, Bonassi G, Mirelman A, Hausdorff JM, Abbruzzese G, Avanzino L. Attentional Control of Gait and Falls: Is Cholinergic Dysfunction a Common Substrate in the Elderly and Parkinson’s Disease? Front Aging Neurosci. 2016 May 9;8:104. Picillo M, Dubbioso R, Iodice R, Iavarone A, Pisciotta C, Spina E, Santoro L, Barone P, Amboni M, Manganelli F. Short-latency afferent inhibition in patients with Parkinson’s disease and freezing of gait. J Neural Transm (Vienna). 2015 Nov;122(11):1533-40.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/central-cholinergic-activity-and-risk-of-falls-in-patients-with-parkinsons-disease-and-freezing-of-gait/