Markers of cognitive decline in PD: The case for heterogeneity.

Cognitive impairment is highly prevalent and has a severe negative effect on health related and perceived quality of life in Parkinson's disease (PD). It is now established that 20-40% of persons with PD will develop cognitive deficits early in the disease. Moreover, the risk of developing dementia is six times higher in PD patients than in age-matched controls and it is estimated that 80% of patients will develop dementia after 20 years of the disease. In order to address these symptoms properly it is crucial to identify very early in the disease the patients who are most likely to develop dementia rapidly. Persons who meet criteria for mild cognitive impairment (MCI) exhibit measurable cognitive deficits but those deficits are not severe enough to interfere significantly with daily life. While the presence of MCI in PD increases the chance of developing dementia, various studies suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. In this paper we comment on various biomarkers associated with cognitive decline in PD, specifically clinical, neuropathological, genetic and neuroimaging ones. We also discuss disrupted functional connectivity in PD-MCI and reveal preliminary results from our own group. We propose that the current studies looking at different types of biomarkers provide support for different causes being associated with cognitive decline in PD. Large-scale multi-disciplinary and multi-modal longitudinal studies are required to identify more specifically the different phenotypes associated with different cognitive profiles and evolution in PD.