Cognitive Impairment in Parkinson’s Disease: What We Know so Far

Abstract

One of the most impactful non-motor manifestations of Parkinson’s disease (PD) is cognitive impairment. Cognitive decline in PD exists as a continuum, with symptoms ranging from normal cognition to mild cognitive impairment (MCI) and finally dementia (PDD). MCI is clinically heterogeneous and its progression varies with cases reverting to normal cognition. On the contrary, when dementia occurs, the decline is usually rapid and stereotyped. The combination of Lewy and Alzheimer’s disease pathology is the most robust pathological correlate of PDD. There are no approved drugs for PD-MCI and the benefit from the only approved symptomatic treatment for PDD is modest. This review aims to present the aspects in which greater evidence exists and summarize the epidemiology, pathogenesis, clinical features, diagnostic approach, and treatment of cognitive dysfunction and dementia in PD.

Keywords:

• Parkinson
• dementia
• mild cognitive impairment
• review
• biomarker
• diagnosis
• treatment

Abbreviations

AChE, acetylcholinesterase; AD, Alzheimer disease; ADAS-cog, Alzheimer’s Disease Assessment Scale; Aβ, Amyloid-β; iRBD, idiopathic REM-sleep behavior disorder; LB, Lewy bodies; DRS-2, Mattis Dementia Rating Scale Second Edition; MCI, mild cognitive impairment; MCI-PD, mild cognitive impairment in the context of Parkinson’s disease; MMSE, Mini-Mental State Examination; MoCa, Montreal Cognitive Assessment; NBM, nucleus basalis of Meynert; PD, Parkinson’s disease; PD-CRS, Parkinson’s Disease-Cognitive Rating Scale; PDD, Parkinson’s disease dementia; ptau, phosphorylated tau; t-tau, total tau; VAChT, vesicular acetylcholine transporter; WMH, white matter hyperintensities.

The authors received no specific funding for this work.

Disclosure

CP: received a grant Rio Hortega from Instituto de Salud Carlos III (CM18/00072). MJM: Honoraria for consulting and lectures from Merz Pharma and Allergan SA; grants from the MJ Fox Foundation (CP041639), Fundacio la Marato de TV3 (288/C/2014) and Fondo de Investigaciones Sanitarias (FIS)-ISCIII (PI17/00096). The authors report no other conflicts of interest in this work.