Cognitive Impairment in Genetic Parkinson's Disease.

A Planas-Ballvé,D Vilas,Antonio Pisani

doi:10.1155/2021/8610285

Abstract

Cognitive impairment is common in idiopathic Parkinson's disease (PD). Knowledge of the contribution of genetics to cognition in PD is increasing in the last decades. Monogenic forms of genetic PD show distinct cognitive profiles and rate of cognitive decline progression. Cognitive impairment is higher in GBA- and SNCA-associated PD, lower in Parkin- and PINK1-PD, and possibly milder in LRRK2-PD. In this review, we summarize data regarding cognitive function on clinical studies, neuroimaging, and biological markers of cognitive decline in autosomal dominant PD linked to mutations in LRRK2 and SNCA, autosomal recessive PD linked to Parkin and PINK1, and also PD linked to GBA mutations.

Highlights

Cognitive impairment is common in Parkinson’s disease (PD)
We focus on clinical studies about cognitive function in genetic PD and summarize findings on neuroimaging and biological biomarkers of cognitive decline in each genetic form of the disease
In autosomal dominant forms of PD, SNCA-PD is most frequently associated with cognitive impairment, with certain mutations clearly increasing the risk of early dementia, such as SNCA triplications and the p.E46 K mutation

Summary

Introduction

Cognitive impairment is common in Parkinson’s disease (PD). Approximately 20–33% of patients have mild cognitive impairment (MCI) at the time of diagnosis [1, 2], and up to 80% of patients develop dementia during the course of the disease [3, 4]. There is an important cognitive heterogeneity between patients, especially in the rate of cognitive decline [8] Some of this variability is thought to be related to extrinsic factors and comorbidities, but genetics may play an important role. A recent systematic review highlighted the role of the genetic risk factors for cognitive decline in PD, with an especial focus on some genetic forms of the disease [9]. Postmortem studies have revealed that cortical and limbic α-synuclein pathology is the hallmark of PD dementia. Coexistent pathology such as amyloid plaques, tau-related pathology, and vascular lesions may coexist and contribute to cognitive decline in PD [11, 12]

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