Neuropsychiatry and Dementia

How much do we really know? And how much of what we know, can we use right now?

By Goldin Joghataie

This is the day and age of neuroscience, specifically, neurodegeneration and neuropsychiatry. But how much of the excitement from the progress we’re making with research impacts patients who are currently on waitlists to be treated by a clinician?

The number of people diagnosed with diseases that have dementia as a symptom is rising rapidly. It is estimated that currently, ~55 million people have dementia.1 This alarming number will grow exponentially in the next thirty years with the aging population.

These increasing numbers are not just because of better diagnostic techniques and public health literacy, but also because of an exponentially growing population of older adults who are facing many risk factors for the disease: loneliness, depression, stress-induced triggering of a hereditary gene, a suddenly activated dormant virus from a previous infection (ex. chickenpox or COVID-19), improper sleep and an unhealthy diet. With all these confounds, uncertainties, and multiple causes, it may seem easier to say that the only way to treat a neurodegenerative disease like Alzheimer’s disease (AD) is to prevent it.

However, the ironic statement of treatment is prevention cannot satisfy the immense pressure and hardship felt by Alzheimer’s patients and their families. Specifically, neuropsychiatric symptoms alone that result from AD cannot be ignored when a person has passed the initial stages of disease onset. “I hear a lot about prevention.

I think prevention is great.”, says Dr. Corinne Fischer, an associate professor in the IMS. “But the reality is that even if you do everything completely right, there is still a risk that you are going to develop dementia and behaviour sequelae of dementia. Some things you cannot prevent entirely, and often by the time we see patients with neuropsychiatric symptoms, the clock is ticking, and they are already manifesting a disorder.”

Dr. Fischer, who has been a geriatric psychiatrist for over 20 years, states that her main interest in research is identifying specific markers and finding the association between neuropsychiatric symptoms in AD and abnormalities in the brain. She finds this to be the most immediate and crucial gap in the field. Most of her work focuses on finding the neural correlates of neuropsychiatric symptoms, specifically psychosis, in dementia among older patients through analyzing brain scans, genetics, pathological markers, and clinical and cognitive markers.

Currently, there are many differing narratives about biomarkers in neurodegeneration. Alzheimer’s disease, for example, has been linked to the aggregation of the misfolded versions of the amyloid beta and tau proteins. In recent years, however, these correlations have been questioned in terms of direct impact, validity, and specificity to the disease.

“There isn’t such a good relationship between a biomarker and clinical disease,”

Dr. Fischer adds. “You can have lots of amyloid pathology and be normal. Or have a little bit and be quite impacted. Even more so with neuropsychiatric symptoms, there isn’t even a basic marker here. Does more tau and amyloid equate to more symptoms? Maybe. Maybe not. But not for sure.” Dr. Fischer also stated that there is no specific age of onset for diseases such as Alzheimer’s, and notes that demonstrable changes in memory, behaviour and general functioning should be the indicators more so than age. “Some say [at] 65 years [of age], but then there are people who are 85 years old and have absolutely no issue, and there are those who are 45 and have significant impairment. I would flag and look out for signs based on clinical symptoms.”

But diagnosing AD based on clinical symptoms isn’t always easy. Mild or common symptoms like anxiety, depression, or apathy often do not even come to clinical attention as people are usually more worried about frontal lobe symptoms such as disinhibition, aggression, and psychosis, which are fortunately not as frequent. However, symptoms of anxiety and depression can be connected to the diagnosis of mild behavioural impairment (MBI), which may suggest that the emergence of these symptoms prior to the onset of cognitive decline could be a marker of dementia. People with MBI are also at more risk for experiencing cognitive decline.

Continuing with this, another part of the puzzle is the chicken and egg situation when it comes to neuropsychiatry. How can

Associate Professor, Division of Geriatric Psychiatry and the Institute of Medical Science, University of Toronto you tell if a present issue such as anxiety or depression is the cause or the result of dementia or AD? In other words, how can one know if a symptom is a prodromal warning sign of neurodegenerative disease onset, or if it is the aftermath of already progressed brain deterioration? Dr. Fischer adds that this issue is also due to the fact that we currently do not have clear, direct, biomarkers that can be identified in brain scans or blood tests.

Dr. Fischer also highlighted that since individuals with dementia often may not recall their situation accurately, a crucial step for clinicians is to get a really good history, specifically collateral history and to ask family members about the patient’s medical background. “You want to know if this is an emergent problem, if it has been there before, or if it is an exacerbation of something that was already there.” Dr. Fischer adds that she also tries to find non-drug approaches that may be helpful to some patients such as redirection from topics that causes them distress or certain activities that will engage them. Patients and their caregivers need effective treatments now.

As students just starting research in the field, it may be useful to wonder: has sharp focus on certain proteins over the past decade, the rush and popularity of publications, somehow diverted us from other discoveries that could have had more impact in terms of finding a direct biomarker? What have we learned from all this specific research and how can we continue?

When it comes to neuropsychiatric treatment, where are we now compared to thirty years ago?

Indeed, it seems that recognizing clinical symptoms is the best bet we have. Onset and prodromal stages are identified through behaviour changes and the majority of medical treatment is for soothing or treating the symptoms. “We [have] some treatments that are actually pretty good, but we need more effective therapeutics specific to neuropsychiatric symptoms in dementia.”

These drugs in themselves have many side effects and though the suggestion is to re-evaluate use every three months, many such medications are prescribed for the long term. What’s more is that many of these drugs (such as antipsychotics) were not made for the older population. “What we typically do now is that we prescribe the same medications that we would prescribe for psychiatric symptoms in a younger person, so they don’t always translate into effectiveness in older people.” Dr. Fischer says that it is important that we tailor treatment for the older demographic with neurodegenerative diseases. We must “distinguish, what is it about these symptoms in dementia or cognitive decline that are different from the same symptoms that we see in people who are younger that have no cognitive decline?”

With this, we can conclude that new research findings need to be assessed for both validity and effectiveness. Data collected regarding dementia and AD must be translated to the clinic and be personcentred. New treatments are needed that will yield significant improvement with the utmost minimum number of side effects that can delay brain deterioration and improve quality of life.

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