Cognitive decline in Parkinson disease

Key Points The full spectrum of cognitive impairment, from subjective cognitive decline to dementia, has been observed in Parkinson disease (PD) Mild cognitive impairment in PD usually progresses to dementia, but can be stable and even revert in some patients The aetiology of cognitive impairment in PD has not been fully elucidated, but limbic and cortical Lewy body pathology seems to be the main cause Amyloid plaque pathology also contributes to cognitive decline in PD, and amyloid pathology detected by cerebrospinal fluid analysis and imaging can predict subsequent dementia Other probable mechanisms include genetics, synaptic pathology, neurotransmitter changes and inflammation Cholinesterase inhibitors have symptomatic effects, but no disease-modifying treatments are available to reduce the risk of dementia in PD Dementia is commonly encountered in advanced stages of Parkinson disease (PD), but evidence is accumulating that cognitive decline can manifest much earlier in the disease course. Aarsland and colleagues review current knowledge regarding cognitive impairment in patients with PD, focusing on cerebrospinal fluid and imaging biomarkers as potential predictors of cognitive decline in this population. Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β 42 , a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE *ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no c