Cognitive Dysfunction in Parkinson’s Disease

With the progressive improvement in the management of the motor symptoms associated with Parkinson’s disease, in the last decades the non-motor aspects of this disorder have gained growing attention by clinical and research communities. Cognitive functioning and its evolution are undoubtedly the most investigated non-motor aspects in PD due to their important implications in the diagnosis and treatment of the disorder as well as in the establishment of the disease functional outcomes. Despite the huge number of studies so far, the nature and the extent of cognitive decline are still poorly understood as well as their relation to disease type, duration and motor features. Heterogeneity has emerged as a key concept when describing the variety of cognitive deficits in PD and the diversity of their underlying neuro-pathophysiological mechanisms (Kehagia et al., 2010; Owen, 2004). Nonetheless, evaluation of the cognitive decline associated with PD is essential for good clinical and pharmacological management of the disease course. Community-based studies of dementia in patients with Parkinson’s disease (PD) have reported prevalence between 28% and 44%. However, longitudinal studies estimating the proportion of patients with PD who will eventually develop dementia reported a 4-year prevalence of dementia of at least 51.6% and an 8-year prevalence of 78% (Williams-Gray et al., 2006). The cumulative incidence of dementia increases with age, with a risk of dementia of 65% by the age of 85 years (Mayeux et al., 1990). It has been widely assumed that cognitive deficits are only a feature of late-stage PD. Recent studies, however, reveal that subtle cognitive abnormalities that are not clinically apparent, mainly involving the executive functions, occur from the earliest stages of the disease (Foltynie et al., 2004a; Levin & Katzen, 2005) In this regard, two global cognitive profiles have been used to define the type of deficits found in PD, namely mild cognitive impairment and dementia. The first is an umbrella definition and has been used to characterize the variety of impairments affecting patients without global and extensive cognitive decline. Disorders can involve one or more cognitive domains among which executive/attention, memory and visuospatial are the most common. Usually, mild cognitive impairment is found in the early and middle stages of disease course and is associated with older age at assessment and at disease onset, as well as to male gender, depression and more severe motor symptoms (Aarsland et al., 2011). Dementia instead is more common in the late stage of the disease and is often preceded by early cognitive impairments. It is characterized by a global cognitive