Neuropsychiatric symptoms in Parkinson’s disease are linked to regional brain atrophy

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Abstract Submission 

Roqaie Moqadam^1,2, Yashar Zeighami³, Mahsa Dadar⁴, Houman Azizi⁵, Alexandru Hanganu^6,7, Lucas Ronat^1,8

¹Faculty of Medicine, university of montreal, Montreal, Québec, ²Douglas Mental Health University Institute, Montreal, Canada, ³Douglas Research Centre, Montreal, Quebec, ⁴McGill University, Montreal, QC, ⁵Montreal Neurological Institute, Montreal, Quebec, ⁶university of montreal, Montreal, Québec, ⁷Faculty of Medicine, University of Montreal, Montreal, Canada, ⁸Quebec Neuroimaging of Emotions Laboratory, Research Centre of University Institute of Geriatric, Montreal, Canada

Roqaie Moqadam  
Faculty of Medicine, university of montreal|Douglas Mental Health University Institute
Montreal, Québec|Montreal, Canada

Yashar Zeighami  
Douglas Research Centre
Montreal, Quebec

Mahsa Dadar  
McGill University
Montreal, QC

Houman Azizi  
Montreal Neurological Institute
Montreal, Quebec

Alexandru Hanganu  
university of montreal|Faculty of Medicine, University of Montreal
Montreal, Québec|Montreal, Canada

Lucas Ronat  
Faculty of Medicine, university of montreal|Quebec Neuroimaging of Emotions Laboratory, Research Centre of University Institute of Geriatric
Montreal, Québec|Montreal, Canada

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Detecting neurodegeneration prior to its clinical presentation is still an ongoing challenge [1]. In PD, the loss of dopamine leads to impairment of the striatal regions. Since the striatum plays a role in cognition (reinforcement learning, decision making, working memory), striatal impairment will affect the frontal cognitive regions [2]. Indeed, previous neuroimaging studies showed that in PD there are changes in the brain morphology in the temporal, dorsolateral prefrontal regions, and striatal dopaminergic circuits. These changes have been reported with respect to gray matter thickness and volumetry [3]. Recent scientific advances have shown that neuropsychiatric symptoms (NPSs) are present early in the disease and are early markers of cognitive decline. In fact, some NPSs manifest even before the clinical presentation of PD. For example, apathy is present in up to 40% of PD patients, but is also present in up to 26% of older healthy individuals. Additionally, recent studies have shown that the prevalence of depression (35%), and anxiety (31%) is higher in PD patients in comparison to older healthy individuals [4-6]. Here we assess the relationship between gray matter atrophy and NPSs in PD, to determine whether greater atrophy is associated with increased likelihood of experiencing specific NPSs and whether these relationships are regionally specific.

Imaging and clinical data were obtained from the Parkinson's Progression Markers Initiative (PPMI) study. Clinical measures included assessments such as the Unified Parkinson's Disease Rating Scale (UPDRS), cognitive evaluations, disease duration, and NPS scores. Specifically, NPS scores corresponding to the Geriatric Depression Scale (GDS), the State-Trait Anxiety Inventory total (STAI_Total), items related to motivation and mood (Apathy) within UPDRS I, and REM Sleep Behavior Disorder (RBD) assessments were included. Deformation-Based Morphometry (DBM) maps were extracted using T1w images in 350 PD patients (607 timepoints). DBM maps were calculated as the Jacobian determinant of the deformation field from the nonlinear transformation of the T1w images to the MNI-ICBM152 template, computed using ANTS [7]. Lower DBM values indicate local shrinkage of tissue; i.e. atrophy [8]. Using Schaefer and Xiao atlases average DBM values in1022 cortical and subcortical regions were measured [9,10]. A series of linear mixed effects models were used to assess the associations between NPSs and DBM, including MOCA, sex, age, handedness, and duration of disease as covariates.

Figure 1 shows the t statistic maps of the significant regions for each NPS. The results showed significant associations between regional GM atrophy as measured by DBM and NPS severity in PD patients for multiple regions and scores. The list of significant subcortical regions include: a) depression: left red nucleus and left subthalamic nucleus, b) REM Sleep Behavior Disorder: right red nucleus right substantia nigra, left subthalamic nucleus, and right thalamus, c) anxiety: bilateral thalamus, d) UPDRS-I: bilateral putamen, bilateral red nucleus, bilateral pallidus interna, bilateral thalamus, left amygdala and right substantia nigra. Colder colors indicate a stronger negative association between DBM values and NPS scores. We found a decrease in average DBM in multiple networks associated with all NPSs (Figure 2) with greater effect sizes in visual network as well as ventral and dorsal attention networks.

NPSs were associated with presence of atrophy in multiple cortical and subcortical regions. These findings suggest that the greater severity of NPSs observed in PD is associated with atrophy in regions implicated in the disease.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ¹

Psychiatric (eg. Depression, Anxiety, Schizophrenia)

Aging

Other Methods

Anatomical MRI ²

Aging

Anxiety

Degenerative Disease

DISORDERS

Neurological

Psychiatric Disorders

STRUCTURAL MRI