However, some patients with PD and memory decline also have changes that are more consistent with neuropathological findings seen in AD. Many PD patients have a mix of the two types of pathology.68, 69 Deficits in the dopaminergic system contribute to cognitive decline, but involvement of the cholinergic and adrenergic systems is also likely. PD autopsy studies have shown significant reductions in neocortical cholinergic neurons.70

Although functional imaging has been used to study motor changes in PD, little work has been done to examine cognitive deficits, despite the high frequency of this symptom in PD. As discussed above, executive dysfunction, Inhibitors,research,lifescience,medical including problems Inhibitors,research,lifescience,medical with planning and set. switching, are common in PD. Some groups have used modified versions of the Tower of London, a planning task, to examine executive performance with functional imaging, and found variable

dorsolateral prefrontal activation changes in PD.71, 72 Lewis et al73 examined early cognitive changes in PD and found reduced activity in frontostriatal circuits during performance of a working memory task. Cholinesterase inhibitors have received the most attention as potential PLK inhibition agents to treat PD dementia. The medications discussed below, donepczil, rivastigminc, galantamine, and memantine (an N-methyl-D-aspartate [NMDA] antagonist), are all approved for use in treatment of AD in the US, but Inhibitors,research,lifescience,medical not for Inhibitors,research,lifescience,medical use in other types of dementia, including that associated with PD. Donepezil has received the most extensive study as a potential therapeutic agent for dementia in PD. Aarsland et al74 performed a double-blind, placebo-controlled, crossover study and found that this medication

was well tolerated in PD patients and did not worsen motor symptoms. Significant positive Inhibitors,research,lifescience,medical effects of donepezil treatment on cognition were seen on objective memory testing and on clinician and caregiver ratings. Open-label studies also suggest, donepczil may be useful in the treatment of hallucinations in PD, but worsening of motor symptoms and delusions have been reported in these studies.75, 76 In addition to possibly improving cognition, rivastigminc has also been found to ameliorate hallucinations and improve behavioral problems. 77, 78 Galantamine, a cholinesterase the inhibitor with additional nicotinic activity approved for use in AD, has been investigated for use in PD dementia, with some positive preliminary results, but. variable effects on motor function.79 Donepezil, rivastigmine, and galantamine may all potentially worsen motor function in PD. Behavioral symptoms, such as hallucinations, may improve with cholinesterase inhibitor treatment, as has been reported in some AD cases treated with these agents. Contraindications to acetylcholinesterase inhibitor use include a history of bleeding gastric ulcers, since these medications will increase gastric secretions.