What does dementia mean?
Historically, the term dementia meant “being out of one’s mind.” Dementia is now more precisely defined, and serves as an umbrella term for numerous conditions that can lead to dementia. The most common cause of dementia is Alzheimer’s disease. Other causes of dementia include vascular dementia, frontotemporal dementia (FTD), Diffuse Lewy Body Disease (DLB), Parkinson’s dementia, to name a few. The term dementia is also known as “Major Neurocognitive Disorder,” and they mean the same thing.
So to say that a person has dementia only tells part of the story. It implies some level of decline in brain function, but it doesn’t say anything about which functions are impaired which would point to a more accurate diagnosis. An analogy would be a say a person has heart disease, which does not tell you the type of heart the disease such as a heart attack, congestive heart failure, or something else. The treatment for different types of heart disease is obviously not the same, and this is also the case for the the different types of dementia.
How is dementia diagnosed?
When you see a dementia expert, brain function is assessed by so-called cognitive domains. They all represent routine activities that we all do every day, but what you might not know is that these routine activities are performed by very distinct regions of the brain. They include:
- Complex attention (multitasking, paying attention to details in a conversation)
- Executive function (planning activities, abstract thinking)
- Memory (short-term and long-term memory function)
- Language (speech fluency, comprehension, word-finding)
- Visual and so-called praxis (navigating familiar and novel environments, using familiar tools)
- Social cognition (out ability to inhibit impulses, following social norms)
Remarkably, each of these complex areas of brain function is located in a fairly unique and well defined area of the brain. For example, a famous patient known as H.M. had severe seizures that could not be controlled with medication, and he therefore underwent surgery where a piece of brain where the seizures originated was removed. This piece happened to be a structure known as the hippocampus, where all our memories are initially formed, which is often severely affected in Alzheimer’s disease. Following surgery, H.M. went to see his doctor for a follow-up, and they had a nice chat. He left the room for a few minutes, and when he returned, H.M. had no recollection of ever seeing his doctor before. The loss of his hippocampus had rendered him incapable of forming new memories. However, he still had vivid memories of his childhood and events before the surgery since long-term memories no longer rely on the hippocampus. This is why someone with Alzheimer’s disease often has excellent long-term memory, but cannot remember a conversation from earlier in the day. As you will learn later, different types of dementia affect different cognitive domains, and this is the way a more specific diagnosis is made in the clinic.
To have a diagnosis of dementia, a person must have a “substantial” decline in cognitive function from a previous level of performance in at least one of the domains listed above. Usually this is a combination of reports from the patient and family as well as more formal testing in the clinic. In addition, the deficits must be severe enough to interfere with independence, for example needing help with finances or grocery shopping when this was not problematic before.
What about mild symptoms (or no symptoms)?
The more we learn about different dementia syndromes, the more we learn that it is more of a spectrum rather than an illness with a distinct onset. You should be familiar with the term “Mild Cognitive Impairment (MCI),” also known as “Minor Neurocognitive Syndrome,” which is essentially a diagnostic category for individuals with noticeable decline in at least one cognitive domain listed above, but the individual is still able to manage finances and taking medications on time without difficulty. As with dementia, MCI is a nonspecific diagnostic category, and only by defining the type of dementia is it possible to predict future progression and start a treatment, if available.
But there is more to the story. In Alzheimer’s disease, we now know that the changes in the brain leading to this illness starts at least 20-30 years before any symptoms, such as memory problems, occur! Hence, I encourage you to look at dementia as a spectrum, with one end being asymptomatic, but with changes in the brain that can eventually lead to symptoms, and, on the other end of the spectrum, severe dementia which may require a care home. Most research you will learn about in future blog posts targets a specific disease stage along this spectrum.
A brief description of the most common types of dementia
Alzheimer’s Disease (AD)
Let’s start with the elephant in the room. Approximately 60% of all dementia is due to AD. The most common, early symptom of AD is forgetfulness, such as forgetting appointments or details of conversations the day before. By far the most typical report from family members is that they have to answer the same question over and over throughout the day. But other cognitive domains can also be the first to cause problems, including language, visual, dysfunction, or changes in social cognition. The main findings in the brain is AD are deposits of amyloid-beta (amyloid plaques), and tau (neurofibrillary tangles). Both of these pathologies can now be identified by spinal fluid testing or brain imaging (PET) to aid diagnosis. You can learn more about AD in a separate blog post.
Vascular dementia
This is a broad category of cognitive impairment due to lack of blood flow to the brain. This can involve a frank stroke, or a slow accumulation of very minor slowing of blood flow due to clogging of the smallest arteries to the brain. The symptoms relate to the location of the stroke, or often impact how quickly a person can process information. AD and vascular changes in the brain often co-exist. It is often distinguished from AD in that while a person might be forgetful, giving small cues, for example reminding the person of the general theme of a conversation will often help with recall.
Frontotemporal dementia (FTD)
The clinical hallmark of FTD is a dramatic change in socially inappropriate behaviour. A few examples would be someone suddenly starting to shoplift, a notable lack of empathy for emotionally charged events, such as a death, or lack f social decorum such as eating off another person’s plate at the dinner table. While AD can rarely present in a similar fashion, these behaviours are most often associated with FTD. But there are also subtypes of FTD which primarily involves language, termed primary progressive aphasias. One especially dramatic variant, known as semantic dementia, leads to the loss of meaning of words. A person with semantic dementia might be presented with a banana, but unable to identify it nor know what to do with it.
Lewy Body and Parkinson’s Dementia
Many years ago a saw a patient in the clinic who was experiencing some unusual symptoms. Over the last several months he had started seeing outlines little animals running in the corner of his eyes. He was aware that these signing were not real, which is what we call visual hallucinations, but they nevertheless seemed real to him. He had also noted a slower gait, and his wife said his posture was more stooped. This would be a typical presentation for Dementia with Lewy Bodies (DLB). It gets its name from so-called Lewy Bodies that are identified in the brain. It is closely related to Parkinson’s Dementia, with the timing of the onset of Parkinson’s symptoms being important. There is ongoing work to develop a diagnostic test measuring Lewy Bodies in the brain or spinal fluid.
The Research Road to a cure
Dementia research is divided into 2 major stages – the preclinical stage, which means work in the lab and prior to testing in humans, and the clinical stage which means human clinical trials. A lot of very exciting work is being done in the preclinical space, and every new drug starts its journey here. Clinical research is divided into 3 stages, or phases, each with a specific purpose:
Phase I: Test for safety and tolerability in humans, test whether drug works as expected
Phase II: Expanded safety and tolerability, start exploring drug mechanisms and treatment effect in more detail
Phase III: This is the crown jewel in clinical drug research. It is a large study to show a drug can treat a specific disease. A positive Phase III trial usually means the drug is headed for approval for human use.