Objective: We aimed to explore cross-sectional grey-matter volume (GMV) and CSF biomarkers differences in PD patients exhibiting a rapid progression of cognitive decline compared to those showing a stable course in a 2-year follow-up.

Background: Cognitive impairment is an essential feature of Parkinson’s disease (PD) which exhibits a variable course. Whereas cognitive status remains relatively stable in some patients, it rapidly evolves to dementia in others. Hence, identifying early biomarkers of rapid progression of cognitive decline represents an urgent need.

Methods: From the Parkinson’s Progression Markers Initiative (PPMI), we identified a homogenous sample of fifty idiopathic, de-novo PD patients with preserved cognitive function (MoCA>27). The sample was grouped as those who remained cognitively stable (n=30) and those who converted to PD-MCI (n=20) in a 2-year follow-up. Groups where matched for age, education, cognition, mood, UPDRS-III and H&Y stage. CSF values of TAU/pTAU, α-synuclein and Aβ-42 were recorded. A VBM of GMV was performed. Between-group comparison was done using age, sex and education as nuisance variables. Regression analysis was performed between the identified clusters of GMV, CSF biomarkers and rate of annual MoCA change.

Results: No between group differences were found in clinical/sociodemographic measures. At baseline, converters showed a significant decrease of posterior-cortical GMV mostly ascribed to the bilateral inferior occipital gyrus, bilateral angular gyrus, bilateral middle and right inferior temporal and frontal gyrus. GMV values in the left angular gyrus (r=0.512;p<0.001), the right visual-association area (r=0.391;p>0.01), the right middle temporal gyrus (r=0.426;p<0.01) and the right inferior frontal gyrus (r=0.449;p<0.01) appeared strongly associated with more severe cognitive change. Increased TAU was associated with decreased GMV in left angular gyrus (r=-0.449;p<0.001), bilateral visual-association areas (r=-0.346;p<0.01), inferior (r=-0.340;p<0.01) and middle temporal gyrus (r=-0.313p<0.01) and higher rate of cognitive decline (r=-0.318;p<0.01).

Conclusions: In de-novo PD, early posterior-cortical changes and related increased TAU pathology appears predictive to rapid cognitive decline. It highlights the relevance of posterior-cortical deficits as biomarkers of more aggressive forms of cognitive deterioration in this population.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/biomarkers-of-rapid-progression-of-cognitive-decline-in-parkinsons-disease/