Basal ganglia amyloid beta accumulation and cognitive dysfunction in Parkinson disease

Introduction: Cognitive dysfunction is a significant sign of Parkinson disease (PD) and the pathophysiology is not well understood. Deposition of amyloid beta (Aβ) is necessary in the pathology of cognitive impairment in Alzheimer’s disease, and there is accumulating evidence suggesting that Aβ may also play a role in PD. However, findings are mixed. While several studies agree that Aβ deposition affects cognitive function in PD, there are mixed findings about cortical and striatal staging of amyloidosis. Furthermore, while the importance of striatal Aβ deposition and its role in PD associated dementia is well described; the pattern of regional deposition in mild cognitive impairment is understudied. Therefore, we tested the hypothesis that regional amyloidosis was associated with domain specific mild cognitive impairment in PD. Fourteen patients diagnosed with PD ages 54 to 77 received a battery of neuropsychological tests surveying attention, working memory, switching, inhibition, verbal fluency and processing speed. They also underwent 3T magnetic resonance imaging and Positron Emission Tomography (PET) with the Aβ radioligand florbetapir F18 (Avid Radiopharmaceuticals, Philadelphia PA). Aβ was quantified using FreeSurfer’s PetSurfer pipeline which provided 100 regions of segmentation with signal output normalized to the pons. Basal ganglia regions were matched for side of disease onset. Aβ accumulation in basal ganglia and prefrontal cortex (middle and superior frontal gyrus) were correlate with cognitive performance using Pearson’s correlation (p<0.005). Bilateral Aβ deposition in the Putamen was correlated with semantic fluency (ipsilateral R² = 0.59, p = 0.001; contralateral R² = 0.45, p = 0.009 (trend)), semantic switch (ipsilateral R² = 0.59, p = 0.001; contralateral R² = 0.64, p = 0.001), switch accuracy (ipsilateral R² = 0.57, p = 0.002; contralateral R² = 0.59, p = 0.001), and processing speed (ipsilateral R² = 0.71, p < 0.001; contralateral R² = 0.69, p < 0.001). Aβ deposition in the contralateral caudate was associated with processing speed (R² = 0.53, p = 0.003). Aβ measures from cortical regions of interest were not consistently correlated with cognitive function. Our findings support previous work showing that Aβ accumulation in the basal ganglia is significantly associated with global cognitive dysfunction and dementia in PD. We extend previous work by describing the relationship between domain specific deficits and regional deposition. While PD associated cognitive dysfunction is generally associated with disruptions in basal ganglia-thalamocortical circuits as a result of dopamine depletion, our findings suggest even sub-clinical Aβ accumulation is another factor potentially contributing to PD associated cognitive dysfunction. Funding for this project was provided by Avid Radiopharmaceuticals, the Biomedical Research Foundation of North Louisiana, and the LSU Health Sciences Center Shreveport Grant in Aid program.