Lancet neurology
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Dementia affects about 40% of patients with Parkinson's disease; the incidence of dementia in these patients is up to six times that in healthy people. Clinically, the prototype of dementia in PD is a dysexecutive syndrome. Loss of cholinergic, dopaminergic, and noradrenergic innervation has been suggested to be the underlying neurochemical deficits. ⋯ On the basis of more recent studies, the main pathology seems to be Lewy-body-type degeneration with associated cellular and synaptic loss in cortical and limbic structures. Alzheimer's disease-type pathology is commonly associated with dementia but less predictive. Recent evidence from small studies suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.
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High iron concentrations in the brains of patients and the discovery of mutations in the genes associated with iron metabolism in the brain suggest that iron misregulation in the brain plays a part in neuronal death in some neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases and Hallervorden-Spatz syndrome. Iron misregulation in the brain may have genetic and non-genetic causes. ⋯ Increased brain iron triggers a cascade of deleterious events that lead to neurodegeneration. An understanding of the process of iron regulation in the brain, the proteins important in this process, and the effects of iron misregulation could help to treat or prevent neurodegenerative disorders.