Early cognitive impairment and motor function

In addition to motor phenotype in established PD-D, what evidence is there for differences in extrapyramidal signs in PD patients with mild cognitive impairment (PD-MCI)? Establishing differences at this point in the disease process could give greater insight into the underlying pathophysiological process. In a community study of 159 patients with incident PD, 36% subjects had some cognitive impairment at baseline assessment, defined as scores of less than one standard deviation (SD) below normative values [29]. Those with global or frontal impairments were significantly older and had more severe motoric disease and lower pre-morbid intelligence than those who were cognitively normal. Longitudinal assessment of the same cohort confirmed that a non-TD phenotype at baseline assessment was a predictor of cognitive decline independent of age, in addition to impairments in more posteriorly mediated cognitive tasks [30]. A cross-sectional study of patients in the Netherlands with early PD found that participants with MCI (defined at a score of 2 SD below the mean score of matched controls in three or more neuropsychological tests) were older, more likely to be male, and had greater disease severity, greater depression scores, and more severe axial and speech symptoms than those who were cognitively normal [31]. However, only age remained a significant predictor of cognitive dysfunction in logistic regression modelling. More recently, in a large study of 121 early, drug-naive PD participants and 100 healthy controls, Poletti et al. [32] reported that bradykinesia, axial impairment, and absence of tremor were associated with an increased risk of MCI, and that patients with PIGD-dominant disease had a higher proportion of MCI diagnoses than those who with TD disease (23.2 versus 6.3%). In contrast, other studies in early PD have not demonstrated differences between axial impairment

[33] or proportion of PIGD phenotype [34] in those with MCI or normal cognition, suggesting that motor phenotype becomes more important as the disease progresses. This has been demonstrated in studies of prevalent PD [35, 36], where subtypes of PD-MCI may be important in further classifying the disorder. In particular, non-amnestic multiple-domain MCI has been found to be linked with motor impairment, with axial functioning/gait making a significant contribution to multinominal logistic regression models of PD-MCI subtype [35].

Taken together, these observations suggest that the pathological processes determining motor phenotype may be dissociated from those determining cognition, either in temporal or spatial evolution or both. By their cross-sectional nature, however, most of these studies were unable to address whether motor phenotype may be an independent risk factor for incident dementia in PD (this is addressed in the next section ‘Motor phenotype as a risk factor for dementia’).

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