Expanding the motor phenotype

PD-D is also an independent risk factor for falls. In a prospective study of 109 subjects with PD evaluated over 12 months, falls occurred in 68% of patients [18]. Previous falls, disease duration, loss of arm swing, and notably dementia were independent predictors of falling. A subsequent meta-analysis of falling in PD was unable to include cognitive impairment and dementia as a predictive variable because this had not been quantified in all of the six studies included [19]. A more recent prospective study determined whether measures of attention were associated with falls in 164 PD patients [20]. A total of 103 (63%) subjects fell once or more during the 12-month study period. Regression analysis revealed an association of fall frequency with poorer attentional scores, which was retained after correcting for UPDRS score. The close association between cognition and falls in PD may in part relate to cholinergic dysfunction [21, 22]; this has implications for the identification of those PD patients most at risk of falling, and for the management and prevention of falls in this patient group. Indeed a small study of PD patients without dementia who had a fall demonstrated a reduction in falls by almost half in those who were taking cholinesterase inhibitors compared with placebo, supporting further work in this area [23].

The PIGD phenotype has also been associated with more frequent excessive daytime sleepiness (EDS) in PD-D, although this association was lost over a 2-year follow-up period, suggesting that the pathophysiology of EDS and motor phenotype is anatomically and/or temporally distinct [24]. Intriguingly, in PD patients without dementia, rapid eye movement sleep behaviour disorder (RBD) is more common in patients with a PIGD phenotype and is associated with greater frequency of falls and reduced levodopa responsiveness [25, 26]. Moreover, the presence of RBD in PD has been strongly associated with more severe symptoms and signs of orthostatic hypotension [26-28]. A phenotypic pattern of PD associated with PD-D is thus emerging, characterized by a PIGD motor disturbance, RBD, EDS, greater autonomic disturbance, and increased frequency of falls.

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