Cognitive decline in Parkinson’s disease: from “The Shaking Palsy” to a more complex paradigm

Parkinson’s disease (PD) was originally considered a pure motor disorder according to the first description by James Parkinson in “The Shaking Palsy”. Nowadays, an increasing awareness of the complexity underlying PD has been acquired among clinicians: dementia is one of the most investigated PD’s non-motor features because of its individual and social burden. Recent evidences report dementia affects up to 80% of PD patients in later stages and it represents a relevant risk for nursing home-admissions and duration of hospitalization. Clinical diagnostic criteria for dementia associated with Parkinson’s disease (PDD) have been suggested to develop common lines of diagnosis. Frequently, PD patients present a state of cognitive impairment since the time of diagnosis, defined as Parkinson’s disease mild cognitive impairment (PD-MCI). In non-demented PD population, MCI is the major predictor for conversion to dementia and new diagnostic criteria and guidelines for diagnostic procedures in PD-MCI have been proposed by Movement Disorder Society to better identified it. The involvement of different circuits including dopamine, norepinephrine and acetylcholine neurotransmission give reason of the multifaceted cognitive profile described in PD patients with mild cognitive impairment and dementia. Main clinical features include attention deficits, executive dysfunction, as well as visuospatial and memory impairments. Neuroimaging and the assessment of genetics, central and peripheral biochemistry and neuropsychology seem to be useful in detecting an early cognitive decline. In particular, the combination of these single biomarkers might make more sensible and specific the early diagnosis of PD-MCI and PDD. In 2012, Cochrane analysis has outlined the therapeutic efficacy of acetylcholinesterase inhibitors (AChEI) in patients with PDD. Among AChEI, rivastigmine is the most recognized treatment that appears to provide a real benefit in cognitive functions, neuropsychiatric disturbances and activities of daily living in patients with PD-MCI and PDD. Some findings suggest possible therapeutic effects in improving cognition of memantine, which is already used in the treatment of Alzheimer’s disease. Also atomoxetine, a selective norepinephrine reuptake inhibitor, showed beneficial for PD’s non-motor symptoms linked to the loss of norepinephrine neurons such as global cognition (i.e. attentional modulation) and daytime sleepiness. Finally, the treatment of motor-symptoms with levodopa has demonstrated a positive impact on some cognitive impairments such as working memory