Objective: To investigate cognitive performance across the Parkinson-Alzheimer’s spectrum and its association with plasma biomarkers and regional CT.

Background: While PD and AD are neurodegenerative syndromes with distinct clinical features, overlap exists in terms of their cognitive presentation. This is particularly the case in late-onset, sporadic cases where co-pathologies of α-synuclein, β-amyloid, and tau have been commonly identified in autopsy cohorts. We investigate how plasma biomarkers of AD, astrocytosis and axonal damage and CT impact cognitive performance across the AD-PD spectrum.

Method: 289 participants diagnosed with PD +/- mild cognitive impairment or dementia (PDMCI/PDD; N=77), PD-normal cognition (PD-NC; N=48), ADMCI/AD dementia (ADMCI/ADD; N=121) and healthy controls (HC; N=44) were included. Plasma measures of p-tau181, Neurofilament Light chain (NfL) and glial fibrillary acidic protein (GFAP) together with FreeSurfer-derived CT were ascertained. Data from a comprehensive neuropsychological battery was also included. Depending on data type, appropriate statistical models were performed with relevant covariates.

Results: Global CT was reduced in all patient groups relative to controls [Figure 1 A]. A similar pattern of regional CT reduction relative to HC was identified across the PDMCI/PDD and ADMCI/ADD groups [Figure 1 B]. Across all groups, p-tau181, GFAP and NfL were associated with CT reductions, particularly in lateral temporal and medial parietal regions [Figure 2 A]. Reduced CT was seen in the regions associated with plasma biomarkers in the ADMCI/ADD and PDMCI groups, but not in the PD-NC or HC groups [Figure 2 B]. In those with MCI/dementia due to PD or AD, [Figure 3] demonstrates that CT mediated the relationship of p-tau181 and GFAP with both delayed recall and executive functions.

Conclusion: There are similar patterns of regional CT reductions across the spectrum of MCI/dementia associated with PD and AD. Elevated plasma p-tau181 and GFAP are associated with worse memory and executive functions and are mediated through reductions in CT. This suggests that cognitive impairment in both PD and AD may be related to the deposition of β-amyloid, and tau, as well as astrogliosis explaining clinical and neuropathological overlap between these neurodegenerative diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-overlap-between-parkinson-disease-pd-and-alzheimers-disease-ad-is-associated-with-plasma-biomarkers-and-their-impact-on-regional-cortical-thickness-ct-an-ondri-study/