Parkinson disease and dementia with Lewy bodies: Clinical sciences

Parkinson disease and dementia with Lewy bodies are two related neurodegenerative conditions due to an abnormal accumulation of alpha-synuclein protein and neuronal loss. Both conditions are characterized by motor symptoms known as parkinsonism, and cognitive decline. Clinically, you can differentiate these conditions based on the timing of onset and severity of motor and cognitive symptoms. Keep in mind that Lewy body dementia is not the same thing, and is a broader term that includes Parkinson disease dementia and dementia with Lewy bodies.

Now, if your patient presents with a chief concern suggesting Parkinson disease or dementia with Lewy bodies, you should first obtain a focused history and physical examination. History typically reveals a recent onset of slowness of movement, shakiness of the patient’s hands at rest, and in some cases, frequent falls. The physical exam reveals bradykinesia, which refers to slowness of movement as well as a decrease in amplitude or speed with continued movement. Additionally, you will notice a pill-rolling tremor, which is a hand tremor at rest with movements that look like the patient is rolling a pill between their thumb and index finger. Finally, the physical exam will reveal rigidity. Moreover, you may find cogwheeling or cog-wheel rigidity, which is shown if you passively move the patient’s limb and feel a series of stops or stalls.

Now, based on findings of bradykinesia, tremor at rest, and rigidity, you can diagnose parkinsonism, so your next step is to assess the underlying cause. First, you should assess your patient for early-onset dementia, which can help you differentiate Parkinson disease from Parkinson-like syndromes, such as dementia with Lewy bodies.

If you rule out early-onset dementia, suspect Parkinson disease. Next, initiate a trial of dopaminergic therapy, more specifically levodopa and carbidopa. Levodopa is a precursor of dopamine that can cross the blood-brain barrier. Once it reaches the brain, the enzyme DOPA decarboxylase converts levodopa into dopamine, eventually replenishing dopamine levels in the CNS and relieving motor symptoms.

However, DOPA decarboxylase exists almost everywhere in the body, meaning that levodopa can be metabolized into dopamine outside the brain as well. There’s a catch though. Dopamine cannot cross the blood-brain barrier, so the level of levodopa that eventually reaches the brain drops, causing inadequate treatment response.

You can avoid this by giving your patient carbidopa, which is a DOPA decarboxylase inhibitor that doesn’t cross the blood-brain barrier. In other words, carbidopa prevents the conversion of levodopa into dopamine outside the CNS, enabling more levodopa to cross the blood-brain barrier.

Now, some important side effects of levodopa include nausea, orthostatic hypotension, and confusion. Additionally, long-term use of levodopa is associated with levodopa-induced dyskinesias and motor fluctuations. Levodopa-induced dyskinesias refer to uncomfortable hyperkinetic involuntary movements that can affect daily activities. They can look like writhing movements, head bobbing, fidgeting, and arm flailing. On the flip side, motor fluctuations are also known as an on-off phenomenon. The “On” phenomenon refers to the improved functioning of the patient once they take the medication, while the “off” phenomenon refers to the reappearance and worsening of bradykinesia and rigidity.

Once you initiate the trial of levodopa and carbidopa, assess supportive criteria for clinical diagnosis of Parkinson disease. The first two include adequate response to dopaminergic therapy and levodopa-induced dyskinesias. The third one is the presence of a rest tremor of a limb. Finally, the last one includes olfactory loss, such as complete loss or reduction of smell, or cardiac sympathetic denervation documented on nuclear imaging. If your patient meets at least two supportive criteria, you can diagnose Parkinson disease.

Okay, let’s talk about the management of Parkinson disease, which relies on supportive care, including counseling, advance care planning, and caregiver education, but also the management of motor and non-motor symptoms.

First, let’s focus on the treatment of motor features, which can be further subdivided into non-pharmacologic, pharmacologic, and surgical management. Nonpharmacologic management includes physical, occupational, and speech-language pathology therapy. You should also encourage exercising because it might slow down the decline in quality of life and might have both motor and cognitive benefits.

Next up is the pharmacologic management. The first-line treatment includes the combination of levodopa and carbidopa. In younger individuals, you could also consider dopamine agonists as a monotherapy, which work by directly stimulating dopamine receptors in the brain. Some examples include pramipexole and ropinirole. Using dopamine agonists, you can delay the use of levodopa-carbidopa and the development of levodopa-induced dyskinesia. However, dopamine agonists have a higher risk of causing impulse control issues, such as gambling, excessive shopping, and hypersexuality, as well as hallucinations and excessive daytime sleepiness.