Many Parkinson's Patients Also Affected By Depression Or Dementia
11 Jun 2013 "More than a third of Parkinson's patients suffer from dementia," Prof Dr Heinz Reichmann told more than 3,000 experts gathered at the 23rd Meeting of the European Neurological Society (ENS) in Barcelona to discuss the latest developments in the field. Prof Reichmann (University Hospital Carl Gustav Carus, Dresden Technical University), Past President of the ENS, based his figures on a study involving 1,331 German Parkinson's disease patients. 15% of Parkinson's patients suffer collaterally from dementia, 11% from both dementia and depression, and 9% from dementia and psychosis. Virtually all Parkinson's sufferers are affected by dementia if they live long enough. Depression, "although mostly mild to moderate," is yet another fate awaiting at least 40 to 50% of Parkinson's patients, according to Prof Reichmann. Research reveals that cognitive decline and depression often worsen the quality of life more than the movement disorder itself and further inhibit the progress of therapy. This largely applies to other Parkinson-associated symptoms as well, such as constipation, which occurs in 45% of all Parkinson's patients, olfactory loss (90%), double vision (10%) or urinary incontinence (50%). Novel therapeutic approaches According to recent research, dementia in Parkinson's can be traced back to neuronal cytoplasmic inclusions - the so-called "Lewy bodies" - found not only in the substantia nigra, as is usual in PD, but also in the brain stem and the cerebral cortex. Then again, a large part of the nerve cells in these patients dwindle away, cells in the nucleus basalis of the central nervous system that respond to the neurotransmitter acetylcholine. While in many European countries currently only Rivastigmine is approved for the
treatment of Parkinson's dementia other treatments are currently being tested, reported Prof Reichmann. "Several studies are examining the effectiveness of cholinesterase inhibitors in Parkinson's dementia. A recently published study has demonstrated somewhat the effectiveness of Donepezil, while Memantine hardly brings significant benefits." Depression: Wide spectrum of possible treatments Depression, likewise very commonly connected to Parkinson's disease, is mainly caused by the dismantling of those systems which release the monoamine neurotransmitters, as well as from malfunctioning of the frontal lobe and the cerebral cortex. Neuropathology research shows a loss of neurons in the nucleus coeruleus, in some patients also in the raphe nuclei, whereby depression is clearly not just a consequence of reactive behaviour. Parkinson's depression furthermore differs significantly from other forms in that it becomes noticeable in every third Parkinson patient prior to the primary disease symptoms - the motor function - through loss of entrepreneurship and self-esteem, for instance, or through other early symptoms. At later stages, panic attacks and anxiety are common, though mood swings correlate only slightly with the severity of motor impairment. So far, psychosocial support, behavioural therapy, psychotherapy, drug therapy as well as electroconvulsive therapy have proven useful in treating this particular depression variant. ENS Past President Reichmann also suggested, however, that it might be worth considering whether D3 dopamine agonists could positively affect depression: "Ultimately, those circuits connecting the basal ganglia to the frontal regions use D3 dopaminergic receptors." There is, however, not much evidence available yet: Only three randomized control studies devote themselves to those dopamine agonists that respond to D3 receptors. Balancing dopamine levels Motor impairments in Parkinson's are often associated with an incorrect concentration of dopamine in the blood plasma, which is why the attention here should be on continuous dopamine replacement, Prof Reichmann said. Constipation can not only be difficult for patients, but also detrimental to effective therapy: "Blocked bowel movements either delay or completely inhibit the body from absorbing the oral therapy," said the expert.
A triple therapy combining levodopa, carbidopa and entacapone helps encounter the decline of effectiveness at the start of treatment, but the latest studies recommend adding a MAO-B inhibitor or long-acting dopamine agonists to the ongoing levodopa therapy. "That reduces side effects and allows good control of motor impairments," the expert emphasised. However, in an advanced stage of the disease involving alternating periods of good mobility and total rigidity ("on-off phenomenon"), more elaborate treatment is required. Deep brain stimulation and pumps for dyskinesias Deep brain stimulation of the subthalamic nucleus, and more rarely the pallidum, have proven effective in dealing with movement disorders (dyskinesia) that some patients develop as a result of taking levodopa. Most of the results here, according to Prof Reichmann, are "very satisfactory" and initial additional studies also indicate good long-term prognosis, although patients need ever more additional medications over time. Deep brain stimulation, however, should not be applied in cases of severe cerebral blood vessel disease, or of depression, dementia or coagulation disorders. An alternative are pumps - such as Duodopa - whereby a levodopa and carbidopa mixture is introduced directly into the small intestine through a small implanted tube according to a programmable time. Another involves a needle placed under the skin that continuously releases dopamine agonist apomorphine into the blood stream. Both systems also significantly improve motor function and provide steady dopamine replacement. References: 23rd Meeting of the European Society of Neurology (ENS) 2013. ENS Abstract 127: The patient with advanced Parkinson’s Disease European Neurological Society Citations:
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Many Parkinson's Patients Also Affected By Depression Or Dementia 
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