Other Dementia: Lewy Body Dementia

00:00 Now, let's talk about the alpha synucleinopathies. This is that 2nd group of disorders that can present with dementia of the non-Alzheimer's type. And there are 3 conditions that I want you to think about that result from deposition of alpha synuclein or Lewy bodies. The first is Parkinson's disease which can cause a Parkinson's disease dementia late in the course of the illness as a result of deposition of Lewy bodies or alpha synuclein within the brain and cortex. Dementia with Lewy bodies, it's early onset dementia and results from deposition of alpha synuclein primarily starting in the cortex then extending down into subcortical structures. And then multiple system atrophy is an alpha synucleinopathy. So again, there is deposition of alpha synuclein in various regions of the brain including the brainstem cerebellum as well as various areas of cortex depending on the MSA subtype. So let's walk through the spectrum of alpha synucleinopathies and these are Lewy body disorders. That's what we're seeing on the brain and that's the family of disorders that we evaluate in these patients.

01:10 The first is Parkinson's disease dementia, dementia with Lewy bodies, and frank Parkinson's disease. It's important to evaluate in patients who may be presenting with an alpha synucleinopathy whether the cause of that is Lewy body dementia or dementia from Parkinson's disease. And the time course of the onset of their cognitive dysfunction and Parkinsonian symptoms is important. In Parkinson's disease, we see early onset of Parkinson's disease, bradykinesia, rigidity, postural instability, and often tremor and following that over time years later, the development of mild cognitive impairment and then Parkinson's disease dementia.

01:47 So dementia is a late finding in PDD. In contrast, in dementia with Lewy body disease, patients develop early cognitive dysfunction typically within the first 6 months of the onset of their Parkinsonian symptoms and this is critical historical information that differentiates these 2 disorders. This is important because Parkinson's disease is responsive to a number of disease modifying therapies that we may consider not using or patients would be less responsive with dementia with Lewy bodies. Let's talk a little bit more about DLB or dementia with Lewy bodies.

02:22 In terms of epidemiology, this is common, commonly occurs in onsets before the age of 65 so it's younger in onset than what we typically see with Alzheimer's dementia.

02:33 What's going on in the brain? Well here, Lewy bodies are thought to be responsible for impaired mental function related to thinking, movement, behavior, and mood.

02:44 There's abnormal aggregation of protein alpha synuclein within the nerves and that's the chief component of what makes a Lewy body. Lewy bodies are found abundantly in multiple brain areas of people suffering from dementia with Lewy bodies and Parkinson's disease dementia, but the time course of this deposition is different.

03:05 In dementia with Lewy bodies, we see early cortical involvement and then subcortical involvement and the opposite is true with PDD. The presence of Lewy bodies alters the level of neurotransmitter and neuromodulation that occurs and contributes to patient's symptoms. Here, we're looking at what happens both in the brain and histopathologically in patients with dementia with Lewy bodies. We see prominent atrophy late in the disease in several areas; one, the occipital lobe and second is the parietal more than temporal and frontal lobes. This presents with early visual hallucinations, early mood changes and visual spatial dysfunction owing from where the Lewy bodies deposit on the brain. And on the right, we're looking at Lewy bodies. These are these cortical Lewy bodies composed of alpha synuclein that we can demonstrate on this ubiquitin stain. How about the clinical presentation? That's what's happening in the brain. How do patients present? Well, in DLB, we see early onset of hallucinations, sometimes visual hallucinations, sometimes these maybe threatening but often they're non-threatening. They're just there, not bothering the patient or caregiver but may indicate underlying disease pathology.

04:20 Resting tremor is uncommon. We see that commonly in Parkinson's disease or idiopathic Parkinson's disease but much less commonly in patients with dementia with Lewy bodies. We can see REM behavior disorder where patients act out their dreams at night as a result of loss of REM atonia.