The pattern of cognitive impairment in PD-MCI

The cognitive profile associated with PD-MCI is characterized primarily by executive dysfunction, commonly identified as difficulties with planning, sequencing, cognitive flexibility, and problem-solving as well as deficits in working memory and attention [7, 9, 11, 32-34]. Memory impairment, of either the encoding or retrieval type, is common [17, 25, 31]. Procedural memory is also impaired [10]. Posterior cortical deficits may also occur early in the disease [6], with visu- ospatial deficits including poor visual organization and visual-construction [9, 35, 36], which has been found to predict cognitive decline and dementia 3 and 5 years, respectively, after baseline assessment [6, 37]. Language dysfunction is rarely reported in the PD population without dementia, with the exception of deficits in phonemic, semantic, and alternating fluency (e.g. shifting between types of categories or types of phonemic criteria), which have been found to decline over time [38] and with disease severity as measured by Hoehn and Yahr stage [39], as well as to predict a later diagnosis of dementia [6, 40].

Genetic and clinical correlates of PD-MCI

PD-MCI has been associated with various demographic and motor features, including advanced disease, longer disease duration, older age at onset, severe motor symptoms, depression, and male gender [12]. A developing literature exists on the relationship between genetic

risk factors and cognition in PD. Studies examining correlations between mutations associated with PD and the development of dementia have yielded varying results, in part due to methodological constraints (e.g. cross-sectional study design, small sample size, screening tests used as opposed to traditional neuropsychological batteries). These are summarized in the following subsections.


Specific cognitive dysfunction associated with mutations in leucine-rich repeat kinase 2 (LRRK2), a common cause of genetic PD, have not been identified to date in cross-sectional studies [41-44]. Of note, LRRK2 G2019S carriers are more likely to have the postural instability and gait disturbance (PIGD) phenotype, which is more likely to be associated with cognitive impairment. The PIGD phenotype, however, has not been associated with cognitive impairment in cross-sectional studies of LRRK2 G2019S carriers [45].

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