Predicting cognitive decline in Parkinson's disease: can we ask the genes?

Abstract

Parkinson’s disease dementia (PDD) is characterized by progressive cognitive decline, mainly affecting executive functions, which occurs in PD patients at least 1 year after the onset of motor symptoms, when no other causes of dementia can be detected. Such temporal cut-off allows to discriminate between PDD and Lewy body disease (LBD) in which dementia is present since the disease onset, along with parkinsonism, visual hallucinations, and fluctuations in the level of consciousness. The prevalence of dementia in patients with PD is 25%, increasing up to 80% in patients with late onset after 20 years of follow-up. In contrast, PDD has been detected in only 20% of young onset PD patients after a follow-up of more than 18 years (1). Clinical criteria for probable PDD require a diagnosis of PD (2) and a slowly progressive dementia syndrome. Typical cognitive deficits in two of four domains (attention, executive function, visuospatial function, and free recall) and at least one behavioral symptom (apathy, depression/anxious mood, hallucinations, delusions, or excessive daytime sleepiness) must be present. Exclusion criteria include unknown time interval between motor and cognitive symptoms, acute confusion, resulting from systemic diseases or drug intoxication and features compatible with vascular dementia (3). In recent years, several studies have focused on predictive markers of cognitive decline in PD. Clinical, neuroimaging, and molecular markers have been identified. Nonetheless, which markers are most reliable and applicable to clinical practice to predict the long-term prognosis of these patients still needs to be clarified.