So again, this is the second part of a two-part series on neurocognitive and brain disorders. In this module, we are talking about neurodegenerative disorders that are marked by a progressive loss of brain structure and a progressive loss of brain function. We'll be talking about Parkinson's and Alzheimer's, but there are other diseases that also fit in this neurodegenerative category including Huntington's disease and ALS, but we will not have time to talk about those two. So this diseases, it's important to know these are basically incurable. They are progressive and degenerative, and what that means is over time things get worse. Sometimes they get worse more quickly and sometimes the progression is slower, but it is inexorable that things get worse over time. There are also some commonalities across these different disease states, that is between Parkinson's and Alzheimer's. We'll touch more on that later, but basically, the commonalities are a typical protein formations and cell death in the brain. So let's start with Alzheimer's. Alzheimer's disease is an age-related irreversible brain disorder that develops over a period of years. It accounts for about 60-70 percent of the cases of dementia. The most common early symptom is difficulty in remembering recent events. Later symptoms include problems with language and disorientation. So you'll often hear about people with Alzheimer's later in the disease how they leave the house and get lost or can't find their way back. Also mood swings can be a problem. Lack of motivation, poor self-care, and behavioral issues including agitation and aggression can be big issues later on in the disease as well. Gradually, what happens is you also begin to lose bodily functions and eventually all of this leads to death. Typically, the life expectancy after diagnosis is about three to nine years. This is a nice cell graphic. You can follow the link at the bottom if you're interested in looking at it more, but basically shows you the difference between a healthy neuron and a diseased neuron. What you see here at this healthy neurons, you see little microtubules inside the neuron there, and then there's a stabilization provided by these tau molecules, what you see in the top part of the slide. Then in the diseased neuron, what happens is you begin to get the disintegration of these microtubules, and you see here how they're falling apart and there's tangled clumps of tau proteins, and wants to talk about beta-amyloid formation as well. So that basically, you see this process of disintegration of falling apart. So there are three pieces or hallmark pieces to these beta-amyloid plaques. Basically, are comprised of fragments of beta-amyloid peptides, but also mixed with other proteins and some leftover bits and pieces of damaged neurons. So again, amyloid plaques one of the hallmarks, neurofibrillary tangles or NFTs also hallmark. These are found inside the neurons, and basically, it's an abnormal collection of tau proteins. Now normally, tau is required for healthy neurons, but in Alzheimer's disease, these proteins clump together and are part of the mechanism that causes neurons to fail to function normally. Another key piece here is loss of connections between neurons, especially those neurons responsible for learning and memory. So neurons can't survive, and when they lose connections to other neurons, and because of these first two pieces, basically these connections are lost and the neurons die. You also see then regions shrink and in the brain, if you're looking at brain structure, the way it looks in terms of MRI scans is you see a larger ventricle space. So let's talk some more about Alzheimer's. So it's rare, but it does happen that people can develop early onset Alzheimer's as early as they're 30s and 40s and 50s, and part of that we know is related to genetic mechanisms. There's specific gene that we'll talk about that's been identified as playing a causal role in terms of early onset Alzheimer's disease. But 90 percent of Alzheimer's develops after the age of 65 and is probably due to a combination of genetic risk, as well as environmental factors and lifestyle factors. Development pattern of damage in the brain is also different depending on whether the case is an early onset case versus a late onset case. So this is for breaking it down in terms of the progression in different stages. So pre-dementia. A lot of times very early symptoms people might think it's aging or stress, when in fact it's very early signs of Alzheimer's. Here we're talking about mild cognitive difficulties that can begin as early as eight years prior to diagnosis. That involves little deficits or changes in attention and planning and abstract thinking and memory. Sometimes also you'll see depressive symptoms and irritability early on. In the next stage is the early Alzheimer's disease stage. Here we're seeing increasing impairments and the doctor is able to make a more definitive diagnosis regarding Alzheimer's. So in this early stage their older memories and implicit memories like how to do things, those are not yet affected by the disease. When you reach the more moderate stage, you see it more progressive deterioration and it makes it difficult for these patients to be independent. You might see speech difficulties, declining vocabulary, less coordination, increased risk of falling, and long-term memory becomes impaired, and then in the advanced stages basically, these patients are completely dependent on others to take care of them. So diagnosis is usually based on medical history. What the patient's relatives and family members can tell the physician as well as behavioral observations. Sometimes medical imaging, so MRI scans, for example, can exclude other explanations, other pathologies or other forms of dementia. So there were criteria that were established in 1984 for diagnosing Alzheimer's, which involves the presence of cognitive impairment. It's important to note here though that despite having ways to diagnose Alzheimer's disease, a definitive diagnosis to really know it's Alzheimer's requires an examination of brain tissue to actually look at those biological mechanisms that we talked about in the beginning. Another way to diagnose Alzheimer's is DSM 5, actually it's criteria for probable or possible Alzheimer's, and here the criteria is evidence of an Alzheimer's disease gene or family history. All three of the following need to be present which is clear evidence of decline memory/learning, steady progression, gradual decline in cognition, and no evidence of mixed etiology. Then finally, the piece here's the disturbance is not better explained by other diseased states, either cerebrovascular or neurodegenerative or the effects of a drug or other mental neurological or systemic disorders. So this is an important piece especially as it pertains to cannabis and cannabinoids. So agitation and aggression can be an important part of this disease. So as the disease progresses, patients can basically become more agitated and aggressive. What that looks like with agitation is restlessness, and sleeplessness, and pacing, and being worried. The aggressiveness may involve a mashing out verbally or physically like, for example, trying to hit somebody, and obviously when patients are agitated and aggressive, it makes it very difficult for people trying to take care of them. So the goal here is to try and figure out what is the underlying cause of that agitation and aggression and remove it. So sometimes they can be related to being in pain. Depression can be important, anxiety, lack of sleep, and the goal is to try and target these underlying causes. Environmental conditions can lead to agitation and aggressiveness. Serving soiled underwear, sometimes a change in the surroundings will set off the agitation and aggression. Sometimes medications with interaction medications can contribute to agitation and aggression. We're going to switch gears now and talk about what is Parkinson's disease. Parkinson's diseases is a motor system disorder, and the primary symptoms that go on Parkinson's are tremor or trembling in hands, arms, legs, and face, rigidity or stiffness of the limbs and trunk, bradykinesia or slowness of movement, postural instability or impaired balance and coordination, and the symptoms may cause difficulty. You can imagine how they would even with simple tasks. Usually, Parkinson's affects people over the age of 60, but certainly people under the age of 60 also can feel Parkinson's just not as common. Obviously, these symptoms interfere with daily activities, but another piece of this is that depression, other emotional changes often also co-occur with the onset and progression of Parkinson's. So diagnosis is based with a medical history and examinations. If you want to read more about Parkinson's, you can see this link down here at the bottom of the page and get more information about Parkinson's. So it's both chronic and progressive that persists over a long period of time, and what that means is every time syndromes get worse. Sometimes again the progression can be slow. Sometimes the progression can be faster. Obviously, one of the goals here is to slow down the progression of these diseases. So some people can become severely disabled, and others may only experience minor motor disruptions. Again, tremors are major symptom for a lot of these individuals. So the thing here is that even though there's a good deal of variability in terms of the progression, how fast it happens and how some people may experience more symptoms, some less, we would like to have a way to predict how that works but we don't. It's just not possible really yet to predict the trajectory for each individual and not really possible to predict which symptoms they'll have or the intensity of their symptoms. So the process of diagnosing is somewhat similar to Alzheimer's as I alluded to earlier, involves medical history, neurological examination, and the other pieces here too that can be looked at. There are different organizations that have created diagnostic criteria. For example, United Kingdom Queens Square Brain Bank requires slowness of movement plus rigidity, resting tremor, or postural instability, and three or more of the following during onset which is unilateral onset, tremor at rest, progression in time, asymmetry of motor symptoms, and response to levodopa for at least five years. So conclusions. Alzheimer's, it's a progressively neurodegenerative disease that impacts neurocognitive function. As the disease worsens, patients need more and more care and will end up being basically requiring full-time care. Agitation and aggression are commonly related or like issues with depression anxiety, loss of sleep, and the underlying website on. The agitation and aggression that can make caring for these patients difficult. Parkinson's on the hand is characterized by progressive neurological change in the motor system. That typically does involve dopamine, and their primary symptoms here are tremor, stiffness, and loss of balance.