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Brain Amyloid Contribution to Cognitive Dysfunction in Early-Stage Parkinson's Disease: The PPMI Dataset
Eleonora Fiorenzato1, Roberta Biundo1, Diego Cecchin2,3
1Fondazione Ospedale San Camillo IRCCS, Venezia, Italia.
Background:
The pathological processes underlying cognitive impairment in Parkinson's disease (PD) are heterogeneous and the contribution of cerebral amyloid deposits is poorly defined, particularly in the early stages of the disease.
Objective:
To investigate regional [18F]florbetaben binding to amyloid-β (Aβ) and its contribution to cognitive dysfunction in early stage PD.
Methods:
A multicenter cohort of 48 PD patients from the Parkinson's Progression Marker Initiative (PPMI) underwent [18F]florbetaben positron emission tomography (PET) scanning. Clinical features, including demographic characteristics, motor severity, cerebrospinal fluid (CSF), and cognitive testing were systematically assessed according to the PPMI study protocol. For the purpose of this study, we analyzed various neuropsychological tests assessing all cognitive functions.
Results:
There were 10/48 (21%) amyloid positive PD patients (PDAβ+). Increased [18F]florbetaben uptake in widespread cortical and subcortical regions was associated with poorer performance on global cognition, as assessed by Montreal Cognitive Assessment (MoCA), and impaired performance on Symbol Digit Modality test (SDMT). Further, we found that PDAβ+ patients had higher CSF total-tau/Aβ1 - 42 (p = 0.001) and phosphorylated-tau/Aβ1 - 42 in (p = 0.002) compared to amyloid-negative PD.
Conclusion:
These findings suggest that multiple disease processes are associated with PD cognitive impairment and amyloid deposits may be observed already in early stages. However, prevalence of amyloid positivity is in the range of literature age-matched control population. Increased cortical and subcortical amyloid is associated with poor performance in attentive-executive domains while cognitive deficits at MoCA and SDMT may identify amyloid-related dysfunction in early PD.
Insights
Cerebral amyloid deposits are present in early Parkinson's disease (PD) and linked to cognitive decline. Cognitive tests like MoCA and SDMT may help identify amyloid-related dysfunction in PD patients.
Area of Science:
- Neurology
- Neuroimaging
- Biomarkers
Background:
- Cognitive impairment in Parkinson's disease (PD) has heterogeneous pathological causes.
- The role of cerebral amyloid deposits in early PD cognitive dysfunction is not well understood.
Purpose of the Study:
- To investigate amyloid-beta (Aβ) deposition using [18F]florbetaben PET in early PD.
- To determine the contribution of Aβ to cognitive impairment in early PD.
Main Methods:
- Utilized [18F]florbetaben PET imaging in 48 early PD patients from the Parkinson's Progression Marker Initiative (PPMI) cohort.
- Assessed cognitive function through comprehensive neuropsychological testing, including MoCA and SDMT.
- Analyzed cerebrospinal fluid (CSF) biomarkers, including tau and Aβ levels.
Main Results:
- 21% of PD patients showed amyloid positivity (PDAβ+).
- Increased [18F]florbetaben uptake correlated with poorer performance on global cognition (MoCA) and executive function (SDMT).
- PDAβ+ patients exhibited higher CSF total-tau/Aβ1-42 and phosphorylated-tau/Aβ1-42 ratios.
Conclusions:
- Amyloid deposits are detectable in early PD and contribute to cognitive impairment, particularly affecting attention and executive functions.
- Cognitive deficits identified by MoCA and SDMT may indicate amyloid-related dysfunction in early PD.
- The findings highlight the multifactorial nature of cognitive impairment in PD.