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Abstract Background Intracellular deposition of alpha‐synuclein (α‐syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α‐synucleinopathies. Transgenic mouse models overexpressing human α‐syn, are useful research tools in preclinical studies of pathogenetic mechanisms. Such mice develop α‐syn inclusions as well as neurodegeneration with a topographical distribution that varies depending on the choice of promoter and which form of α‐syn that is overexpressed. Moreover, they display motor symptoms and cognitive disturbances that to some extent resemble the human conditions. Purpose One of the main motives for assessing behavior in these mouse models is to evaluate the potential of new treatment strategies, including their impact on motor and cognitive symptoms. However, due to a high within‐group variability with respect to such features, the behavioral studies need to be applied with caution. In this review, we discuss how to make appropriate choices in the experimental design and which tests that are most suitable for the evaluation of PD‐related symptoms in such studies. Methods We have evaluated published results on two selected transgenic mouse models overexpressing wild type (L61) and mutated (A30P) α‐syn in the context of their validity and utility for different types of behavioral studies. Conclusions By applying appropriate behavioral tests, α‐syn transgenic mouse models provide an appropriate experimental platform for studies of symptoms related to PD and other α‐synucleinopathies.

Abstract Introduction Bradyphrenia is a key cognitive feature in Parkinson's disease (PD). There is no consensus on whether information processing speed is impaired or not beyond motor performance. Objective This study aims to explore which perceptual, motor, or cognitive components of information processing are involved in the slowdown affecting cognitive performance. Methods The study included 48 patients with PD (age: 63, 3 ± 8, 18; HY I‐III; UPDRS 15,46 ± 7,76) and 53 healthy controls (age: 60,09 ± 12,83). Five reaction time (RT) tasks were administered to all participants. The average RT in each of the tasks and the percentage of correct answers were measured. Patients with PD were in "ON state" at the time of the evaluation. Perceptual, motor, and cognitive components were isolated by means of a series of ANCOVAs. Results As expected, the motor component was slowed down in patients with PD. Moreover, while patients with PD showed slower RT than controls in all tasks, differences between groups did not exponentially increase with the increasing task complexity. ANCOVA analyses also revealed that the perceptual and sustained alert component resulted to be slowed down, with no differences being found in any of the remaining isolated cognitive components (i.e., response strategy‐inhibition, decisional, visual search, or interference control). Conclusions The results revealed that slowness of information processing in PD was mainly associated with an impaired processing speed of the motor and perceptual‐alertness components analyzed. The results may help designing new neurorehabilitation strategies, focusing on the improvement of perceptual and alertness mechanisms.

Background: Intracellular deposition of alpha-synuclein (α-syn) as Lewy bodies and Lewy neurites is a central event in the pathogenesis of Parkinson's disease (PD) and other α-synucleinopathies. Transgenic mouse models overexpressing human α-syn, are useful research tools in preclinical studies of pathogenetic mechanisms. Such mice develop α-syn inclusions as well as neurodegeneration with a topographical distribution that varies depending on the choice of promoter and which form of α-syn that is overexpressed. Moreover, they display motor symptoms and cognitive disturbances that to some extent resemble the human conditions., Purpose: One of the main motives for assessing behavior in these mouse models is to evaluate the potential of new treatment strategies, including their impact on motor and cognitive symptoms. However, due to a high within-group variability with respect to such features, the behavioral studies need to be applied with caution. In this review, we discuss how to make appropriate choices in the experimental design and which tests that are most suitable for the evaluation of PD-related symptoms in such studies., Methods: We have evaluated published results on two selected transgenic mouse models overexpressing wild type (L61) and mutated (A30P) α-syn in the context of their validity and utility for different types of behavioral studies., Conclusions: By applying appropriate behavioral tests, α-syn transgenic mouse models provide an appropriate experimental platform for studies of symptoms related to PD and other α-synucleinopathies., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Bradyphrenia is a key cognitive feature in Parkinson's disease (PD). There is no consensus on whether information processing speed is impaired or not beyond motor performance., Objective: This study aims to explore which perceptual, motor, or cognitive components of information processing are involved in the slowdown affecting cognitive performance., Methods: The study included 48 patients with PD (age: 63, 3 ± 8, 18; HY I-III; UPDRS 15,46 ± 7,76) and 53 healthy controls (age: 60,09 ± 12,83). Five reaction time (RT) tasks were administered to all participants. The average RT in each of the tasks and the percentage of correct answers were measured. Patients with PD were in "ON state" at the time of the evaluation. Perceptual, motor, and cognitive components were isolated by means of a series of ANCOVAs., Results: As expected, the motor component was slowed down in patients with PD. Moreover, while patients with PD showed slower RT than controls in all tasks, differences between groups did not exponentially increase with the increasing task complexity. ANCOVA analyses also revealed that the perceptual and sustained alert component resulted to be slowed down, with no differences being found in any of the remaining isolated cognitive components (i.e., response strategy-inhibition, decisional, visual search, or interference control)., Conclusions: The results revealed that slowness of information processing in PD was mainly associated with an impaired processing speed of the motor and perceptual-alertness components analyzed. The results may help designing new neurorehabilitation strategies, focusing on the improvement of perceptual and alertness mechanisms., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)