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
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
23rd Meeting of the European Society of Neurology (ENS) 2013.
ENS  Abstract  127:  The  patient  with  advanced  Parkinson’s  Disease  
European Neurological Society
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