Nucleus accumbens atrophy in Parkinson's disease (Mavridis' atrophy): 10 years later.

Am J Neurodegener Dis 2022;11(2):17-21 www.AJND.us /ISSN:2165-591X/AJND0137531 Review Article Nucleus accumbens atrophy in Parkinson’s disease (Mavridis’ atrophy): 10 years later Ioannis N Mavridis1, Efstratios-Stylianos Pyrgelis1,2 “C.N.S. Alliance” Research Group, Athens, Greece; 21st Department of Neurology, “Eginition” Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece 1 Received July 20, 2021; Accepted May 10, 2022; Epub June 20, 2022; Published June 30, 2022 Abstract: Parkinson’s disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. The human nucleus accumbens (NA) is a major part of the ventral striatum and modulator of the reward network of the brain. It plays an important role in several cognitive and emotional functions. In patients with PD, dysfunction of this nucleus is correlated not only with movement disorders but also with various neuropsychological deficits and psychiatric symptoms. The human NA suffers atrophy in PD, which is called Mavridis’ atrophy (MA), a well established characteristic of PD that was first described 10 years ago. The purpose of this article is to review the current knowledge regarding the clinical significance of MA. We currently know that it begins in early-stage PD patients, precedes clinical phenotype, and is part of the degeneration of the dopaminergic nigrostriatal system in these patients. MA has several clinical consequences. It is, more specifically, associated with the expression (and severity) of specific neuropsychiatric PD symptoms, namely cognitive impairment, apathy, disinhibition, and impulsive behavior, while its association with motor symptoms remains unclear. MA was recently suggested as a marker of global dysfunction in the mesocorticolimbic network. With new research data, new questions about MA emerge and further research is obviously necessary in order to effectively apply MA, as an imaging finding, to clinical practice. Keywords: Apathy, cognitive impairment, disinhibition, Mavridis’ atrophy, nucleus accumbens, Parkinson’s disease Introduction Parkinson’s disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy [1]. It is an archetypal disorder of dopamine dysfunction characterized by motor, cognitive, behavioral and autonomic symptoms. Besides motor manifestations, neuropsychiatric symptoms occur in the majority of patients. The latter include dementia and cognitive impairment, depression, dysthymia, anxiety disorders, psychosis, apathy, sleep disorders, sexual disorders and treatment-related psychiatric symptoms. Neuropsychiatric symptoms in PD significantly affect mortality, disease progression and patients’ and caregivers’ quality of life [2]. The striatum belongs to the basal ganglia system and is critically involved in motor functions and motivational processes. The dorsal striatum is central to the motor control and motor learning and the ventral striatum, particularly the nucleus accumbens (NA), is essential for motivation and the reward system. This system is dysfunctional in movement disorders, such as PD, and in psychiatric disorders [2]. The human NA is a major part of the ventral striatum [2] and is considered to be a modulator of the brain’s reward network. Some authors consider the NA as a node between executive control network and reward network through its projection to the frontal cortex and limbic pathway. It therefore plays an important role in several cognitive and emotional functions [3]. In patients with PD, dysfunction of this nucleus is correlated not only with movement disorder but also with various neuropsychological deficits and psychiatric symptoms [3]. The human NA suffers atrophy in PD, which is called Mavridis’ atrophy (MA) [2, 4-7], a finding that was first described 10 years ago [8]. In the Mavridis’ atrophy: 10 years later light of recent research data over the last decade, the purpose of this article is to review the current knowledge regarding the clinical significance of MA. Nucleus accumbens atrophy in Parkinson’s disease MA begins in early-stage PD patients and is correlated with psychiatric and cognitive symptoms that occur in PD, mainly apathy and impulsive behavior. As a pathological process, it is part of the degeneration of the dopaminergic nigrostriatal system in PD patients and, thus, precedes clinical phenotype [7]. Recent volumetric imaging studies have confirmed shrinkage of the NA, among other nuclei, in patients with PD, even in those without cognitive impairment [9, 10]. Nyberg et al. (2015) found a significant shape difference in the right NA between PD patients and controls and between different motor subtypes (i.e., tremor dominant and postural instability gait dominant) [1]. Shape differences were driven by positive deviations in the tremor dominant subtype. The authors suggested that their findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway [1]. Interestingly, imaging alterations of the NA have also been revealed in atypical parkinsonian syndromes [11]. At a molecular level, genetic factors associated with PD can affect α-synuclein expression in the NA [12]. Mak et al. (2015), found that, at baseline, patients with PD and mild cognitive impairment, which is associated with progression to dementia, demonstrated widespread cortical thinning compared to controls and atrophy of the NA compared to both controls and subjects with PD with no cognitive impairment [13]. In peri-operative studies of patients with PD, it has been shown that the left NA volume appears to be correlated with cognitive decline after bilateral stimulation of the subthalamic nucleus [14]. Atrophy of the left NA (and frontal cortical areas) has also been associated with mild cognitive impairment in patients with PD [14]. It seems, however, that left NA atrophy is not the real cause of cognitive decline, rather a “marker” of global dysfunction in the mesocorticolimbic network. This is further supported by the correlation of left NA atrophy with atrophy of the left orbitofrontal cortex [14]. 18 NA and frontotemporal (mainly frontal) cortical atrophy, independently contribute to neuropsychiatric symptoms of patients with PD [15]. Apathy is a common neuropsychiatric disturbance in PD patients. A combination of impaired reward processing and compromised mesocorticolimbic pathways could explain the clinical expression of apathy in PD patients [16]. Martinez-Horta et al. (2017) found significant volume loss of the left NA in non-demented, nondepressed PD patients with apathy [16]. MA has also been found to correlate with the presence and severity of disinhibition in patients with PD [15]. Finally, impulse control disorders occur in a subset of patients with PD who are receiving dopamine replacement therapy [17]. Although MA has been correlated with impulsive behavior [7], Pellicano et al. (2015) found volume loss in the NA of PD (...truncated)