Clinical and pathological predictors of cognitive impairment in Parkinson's disease

• Grant number: 22/14421-7
• Support Opportunities: Scholarships abroad - Research
• Start date: March 01, 2023
• End date: June 30, 2023
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Jacy Bezerra Parmera
• Grantee: Jacy Bezerra Parmera
• Host Investigator: Thomas Treharne Warner
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University College London (UCL), England

Abstract

Parkinson's disease is the second most common neurodegenerative disease. It is characterized by the accumulation of alpha-synuclein in the brain, leading to the formation of Lewy bodies, and by the depletion of nigrostriatal dopaminergic neurons. PD dementia (PDD), in turn, represents one of its most relevant non-motor manifestations and is among the primary sources of stress for caregivers. Such cognitive decline in PD is characterized by three main factors: cortical alpha-synuclein deposits and beta-amyloid protein deposits, cortical cell loss, and degeneration of subcortical nuclei. Furthermore, there are several clinical predictors of progression to PDD, including age at onset, time of disease progression, and predominantly axial and rigid-akinetic clinical phenotype. The motor characteristics of PD in this phenotype are balance and gait deficits, which lead to an increased risk of falls and reduced quality of life. In addition, it is increasingly recognized that these are not pure motor tasks but that cognition is also essential for proper mobility, primarily through executive and attentional functions. Previous studies suggest that gait alterations may be clinical predictors of cognitive decline, but few longitudinal data display neuropathological assessments. The present study aims to investigate, through longitudinal data from PD patients with postmortem histopathological assessment, if the presence of recurrent falls and worse gait performance are correlated with a shorter time of evolution to PDD, as well as if there are common anatomical regions to such clinical outcomes. In addition, this study will also assess whether different pathologies, such as beta-amyloid and tau, predict longitudinal cognitive decline in PD. The results will guide further research on the pathophysiological features of PD and its cognitive impairment, as well as possibly support new therapeutic strategies.Keywords: Parkinson's disease; parkinsonian disorders; movement disorders; dementias