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.
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.
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.
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.
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.
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.
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.
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.