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Hippocampal and entorhinal cortex atrophy across the Parkinson’s disease cognitive impairment spectrum (S39.004)

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... Treatment options for dementia in PD are limited (16,23) but dementia is associated with decreased quality of life (44,45), increased incidence of nursing home admissions (67), increased carer burden (50) and increased mortality (46) in this disorder. The etiology of cognitive decline in PD is incompletely understood but is reported to be associated with proteinopathology (42), dopaminergic dysfunction (30), cholinergic dysfunction (26,64) and atrophy within the hippocampus (19,60). This widely varying pathology suggests that endogenous factors which maintain hippocampal function may be altered in PD. ...
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Growth factors can facilitate hippocampus‐based learning and memory and are potential targets for treatment of cognitive dysfunction via their neuroprotective and neurorestorative effects. Dementia is common in Parkinson's disease (PD), but treatment options are limited. We aimed to determine if levels of growth factors are altered in the hippocampus of patients with PD, and if such alterations are associated with PD pathology. Enzyme‐linked immunoassays were used to quantify seven growth factors in fresh frozen hippocampus from ten PD and nine age‐matched control brains. Western blotting and immunohistochemistry were used to explore cellular and inflammatory changes that may be associated with growth factor alterations. In the PD hippocampus, protein levels of the glial cell line‐derived neurotrophic factor (GDNF) were significantly decreased, despite no evidence of neuronal loss. In contrast, protein levels of fibroblast growth factor 2 (FGF2) and cerebral dopamine neurotrophic factor (CDNF) were significantly increased in PD compared to controls. Levels of the growth factors epidermal growth factor (EGF), heparin binding epidermal growth factor (HB‐EGF), brain‐derived neurotrophic factor (BDNF) and mesencephalic astrocyte‐derived neurotrophic factor (MANF) did not differ between groups. Our data demonstrate changes in specific growth factors in the hippocampus of the PD brain, which potentially represent targets for modification to help attenuate cognitive decline in PD. This data also suggests that multiple growth factors and direction of change needs to be considered when approaching growth factors as a potential treatment for cognitive decline. This article is protected by copyright. All rights reserved.
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