Pedro Renato d. Brandão ^1,2* Danilo A. Pereira ³ Talyta Grippe ⁴ Diogenes D. Bispo ^5,6* Fernando B. Maluf ^6* Ricardo Titze-de-Almeida ^7* Brenda M. de Almeida e Castro ^1,2* Renato Munhoz ^4,8 Maria Clotilde H. Tavares ^1* Francisco Cardoso ^9*

• ¹ Laboratory of Neurosciences and Behavior, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, Brazil
• ² Hospital Sírio-Libanês, Brasília, Brazil
• ³ Brazilian Institute of Neuropsychology and Behaviour, Rio de Janeiro, Brazil
• ⁴ Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada
• ⁵ University of Brasilia, Brasilia, Brazil
• ⁶ Department of Radiology, Hospital Santa Marta, Taguatinga, Distrito Federal, Brazil
• ⁷ Central Institute of Sciences, University of Brasilia, Brasília, Brazil
• ⁸ Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
• ⁹ Movement Neuroscience Center, Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort. Material and Methods: This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (n = 36) and PD-MCI (n = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer. Results: Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm2 cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions. Conclusion: PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.