Precision medicine has emerged as a central element of healthcare science and is beginning to change the way we view, diagnose, and treat many diseases and disorders. Precision medicine has already made its mark in several branches of medicine, including oncology, endocrinology, and psychiatry. Neurology is not far behind.

Like many diseases, neurological diseases are not necessarily binary—in other words, we cannot encapsulate a disease like Alzheimer’s to someone either having the disease or not having the disease. Neurological diseases are complex, and their pathologies manifest themselves uniquely in each individual. 

Let’s take a deeper look into how precision medicine fits into the neurology space, including the concept of disease continuums, current and future applications of precision medicine in neurology, and the world’s leading Precision Neurology platform and app-based medical device.

Precision Medicine in Neurology: Disease Continuums

Similar to cancer, many neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia, can be thought of as continuums in which the presence and manifestations of the diseases are different depending on the stage of the disease. Because neurological diseases have so many mixed etiologies, understanding this continuum can be quite challenging. 

For example, one of the underlying pathological mechanisms of Alzheimer’s disease is the aggregation of amyloid. In Alzheimer’s disease, a mechanism such as amyloid may be present in both preclinical and moderate Alzheimer’s patients; however, in the preclinical stage, it is characterized by a smaller aggregation of amyloid compared to in the moderate stage.

However, protein levels in the brain may not be the best indicator of precisely where an individual lies on the disease continuum. It isn’t clear if the development and progression of beta-amyloid plaques accurately and consistently correlate with neurocognitive decline.

Current Applications of Precision Medicine in Neurology

Taking a more precise, personalized approach to neurological diseases will give rise to a breadth of targeted drugs and therapies that can be effectively used in combination to treat specific neurocognitive impairments that present uniquely in neurological disease patients.

Currently, we are seeing a definite shift towards the incorporation of precision medicine in neurology. Data from multiple sources are being combined to create more personalized neurological disease diagnoses and prognoses. These data sources range anywhere from family history and whole genome sequencing to the whole body and brain magnetic resonance imaging and computed tomography imaging. The use and understanding of highly personalized data allow healthcare providers to move away from a “one size fits all” approach and move towards a precise, personalized, and more effective treatment and care planning approach.

Today, utilizing this precision approach in neurology is not feasible at scale due to the inaccessibility and cost of obtaining such large quantities of personalized data, often through costly imaging and diagnostic procedures. 

Future Applications of Precision Medicine in Neurology

This is where digital tools such as portables and wearables will come into play—the future of precision medicine in neurology lies in multimodal digital data, enabling the principles of precision medicine to be applied in neurological disease diagnostics, treatment, and monitoring at scale, expanding the benefits to everyone. 

When large quantities of digital neurocognitive function data sets from healthy individuals and those impacted by specific neurological diseases are combined with strong analytical tools, we can determine new links, patterns, and complex disease signatures associated with a breadth of neurological diseases. This method offers a highly accessible, cost-efficient, and non-invasive approach for diagnosing neurological diseases early, placing an individual precisely along a disease continuum, and providing the most effective possible treatment pathway.

Sleep is a crucial, yet often neglected, factor for overall health and well-being. According to a CDC study, more than a third of American adults are regularly not getting enough sleep. Many know that consistently getting a good night’s sleep can help us be more alert, concentrate on tasks, and increase our productivity, but research has also unveiled a clear connection between sleep and brain health.

In the short term, lack of adequate sleep can affect our judgment, mood, and ability to learn and retain information. In the long term, chronic sleep deprivation may increase the risk of developing dementia later in life.

However, there is plenty we can do to improve our sleep and brain health. Let’s take a look into some simple changes you can make that may improve your sleep, increase focus and productivity, and reduce the risk of developing dementia.

Habits for Improved Sleep and Brain Health

Having good sleep habits, or “sleep hygiene,” to incorporate into your daily routine can help you sleep better, improve your day-to-day brain function, and reduce the risk of developing dementia later in life. 

Here are our top five tips for better sleep.

1. Be Consistent: Stick to a Sleep Schedule

For adults aged 18-60, the CDC recommends seven or more hours of sleep per night. For adults aged 61-64, seven to nine hours are recommended, and for adults aged 65 and older, seven to eight hours are recommended.

Try to go to bed and wake up at the same time every day—yes, even during the weekend. Being consistent reinforces your body’s sleep-wake cycle, making it easier to go to sleep at your normal bedtime and wake up at the time you normally rise.

Lying in bed for hours on end without being able to sleep can be frustrating. If you are unable to fall asleep within 20 minutes, leave your bedroom and do a relaxing activity, such as reading a book, listening to music, or meditating.

2. Set Yourself Up for Success: Limit Your Daytime Naps

Long naps during the day can interfere with nighttime sleep. We all love and deserve an occasional nap, so when you do nap, try to keep it to 30 minutes or less earlier in the day. If you find yourself in an afternoon energy slump and are gravitating towards your bed, consider taking a walk outside, having a glass of ice water, or a phone call with a friend.

3. Stay Active: Incorporate Physical Activity in Your Daily Routine

Regular physical activity during the day can promote restful sleep. In the past, experts have recommended not exercising at night as part of good sleep hygiene; however, newer studies suggest you can exercise in the evening so long as you avoid vigorous activity for at least one hour before bed.

4. Set the Mood: Create a Restful Sleep Environment

When it’s time for bed, make sure your bedroom is quiet, dark, relaxing, and at a comfortable temperature. Exposure to light can make it more difficult to fall asleep, so be sure to close the curtains, put away your cell phone and computer, and turn off the TV. If you’re bothered by noise, consider using some earplugs. You can also turn on a fan or white noise machine if this helps you sleep.

5. Be Mindful: Pay Attention to What You Eat and Drink

Avoid large or heavy meals within a couple of hours of your bedtime. Be mindful of how caffeine affects you—while some can drink coffee throughout the evening, others are more strongly affected and may need to stop drinking caffeinated beverages in the afternoon. Nicotine and alcohol can also impact your ability to fall asleep and get a restful night’s sleep. The stimulating effects of nicotine can take hours to wear off and can impact your quality of sleep. While alcohol can initially make you feel sleepy, it can disrupt your sleep later in the night.

Tracking Your Sleep and Monitoring Your Brain Health

While making changes to improve sleep and brain health, you will likely want a way to quantitatively track and monitor your sleep patterns as well as your brain health. For tracking sleep, there are a wide variety of sleep trackers available, including those integrated into some smartwatches. At a minimum, you’ll want to look at your sleep duration as well as the time you fell asleep and the time you woke up to make sure you’re sticking to your sleep schedule. Some sleep trackers will even track the phases of your sleep cycle.

For monitoring how these changes are affecting your brain function and brain health, consider using a digital brain health assessment tool. 

Around the globe, there has been increased awareness surrounding health and wellness as consumers begin to take their health into their own hands and embrace digital health technologies. With recent advancements in brain disease diagnostics, treatments, and therapies, more individuals are starting to think about their brain health and dementia prevention at a younger age.

Historically, dementia has been perceived as a devastating condition, but this perception is beginning to shift. Our knowledge of dementia prevention and the range of modifiable risk factors has grown immensely.

For example, research has not only continued to further our understanding of the link between the brain and the heart but it’s also advanced our interventions for at-risk patients. By living a healthier lifestyle, modifying many of the risk factors for dementia and cardiovascular diseases, such as stroke, can aid in the prevention of such diseases. However, is stroke a risk factor for dementia?

Below we detail everything you need to know about stroke and dementia, including how to reduce risk factors for stroke and dementia and the best way to understand your risk and monitor your brain health.

Yes, Stroke is a Risk Factor for Dementia

Research shows that stroke is a risk factor for dementia—more specifically, it is a risk factor for vascular dementia. In addition to conditions that reduce blood flow to the brain, such as brain hemorrhages and chronically damaged or narrowed blood vessels, stroke can cause vascular dementia. Depending on the severity of the stroke and the location of damage or tissue death, the degree and range of symptoms of vascular dementia can widely vary. Both cognitive and functional impairments may be present depending on what regions of the brain are affected.

It’s important to note not everyone who has a stroke will later develop dementia. Approximately 20% of individuals who have a stroke develop post-stroke dementia within the following six months. Individuals who have multiple strokes may be at higher risk for developing dementia.

Vascular dementia related to stroke includes stroke-related dementia, post-stroke dementia, single-infarct dementia, and multi-infarct dementia.

Stroke-Related Dementia

When the blood supply to a portion of the brain is abruptly cut off, this is known as a stroke. Typically, a narrowed blood vessel in the brain is blocked by a clot that formed in the brain or the heart of an individual with heart disease. Strokes can vary in severity depending on the location of the blocked vessel and the duration of interrupted blood flow.

Post-Stroke Dementia

When blood flow in a large vessel in the brain is abruptly and permanently cut off, this is known as a major stroke. Major strokes most commonly occur when the vessel is blocked by a clot (ischemic stroke) but can also occur due to the vessel bursting and bleeding into the brain (hemorrhagic stroke). The interruption of blood supply to the brain deprives the brain of oxygen and results in the death of a large amount of brain tissue.

Single-Infarct and Multi-Infarct Dementia

When a medium or large blood vessel is blocked by a clot, a small stroke can occur, causing single-infarct dementia. Often, these strokes are so small that affected individuals may not even notice symptoms or be aware that they occurred. 

Multi-infarct dementia is caused by two or more small strokes. When medium or large blood vessels become blocked with clots, blood supply may be cut off for several minutes, leading to an infarct, or small area of dead tissue, within the brain. 

Reducing Risk Factors for Stroke

While stroke is a risk factor for dementia, it is a potentially modifiable risk factor. The following elements of healthy living may improve heart health, reduce the risk of stroke, and consequently, may help protect the brain:

• Quitting smoking
• Maintaining blood pressure, cholesterol, and blood sugar within recommended ranges
• Eating a healthy and balanced diet
• Exercising regularly 
• Limiting alcohol consumption

Understand Your Risk and Monitor Your Brain Health

When taking steps to modify risk factors to improve brain health and prevent the future development of dementia, you will likely want to measure and monitor your overall health and brain health over time. This will help you understand how your changes are affecting your brain health.

The heart pumps approximately 20 to 25 percent of the blood in your body to your head with every beat. From here, your brain cells use at least 20 percent of the oxygen and food carried by the blood. Your brain relies heavily on your heart to function properly—a healthy heart ensures that a sufficient amount of blood is pumped to the brain, while healthy blood vessels ensure the oxygen-rich blood reaches the brain.

Research has continued to further our understanding of the connection between the cardiovascular system and the brain. This link, known as the brain-heart connection, has deepened our knowledge of how to reduce the risk of developing dementia and neurological diseases, provide early intervention for at-risk individuals, and improve the clinical management of patients.

Let’s take a closer look into the brain-heart connection, heart health and dementia risk, and positive lifestyle changes you can make today to promote heart and brain health.

The Brain-Heart Connection and Dementia

The risk of developing several causes of dementia, such as vascular dementia and Alzheimer’s disease, is believed to be increased by several conditions that damage the heart and blood vessels. 

Alzheimer’s disease and vascular dementia are the two most common causes of dementia, both of which can be linked back to poor heart health, in addition to several other risk factors. In general, vascular dementia is caused by conditions that reduce blood flow to the brain, such as stroke, brain hemorrhages, or chronically damaged or narrowed blood vessels in the brain or at any location in the body. 

Alzheimer’s disease, on the other hand, has a more complex pathology and is believed to be multifactorial, meaning it is not caused by a single factor, but rather develops from a combination of several factors, such as genetics, environment, and lifestyle. However, vascular conditions, as well as risk factors for vascular conditions, have been identified as risk factors for developing Alzheimer’s disease.

Vascular-Related Risk Factors for Dementia

Vascular conditions, including stroke and heart disease, and other health problems known to increase the risk of developing vascular conditions, including high blood pressure, high cholesterol, type 2 diabetes, and obesity, have been linked to an increased risk of cognitive decline and dementia.

Modifiable risk factors for Alzheimer’s disease, including diabetes, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and low educational attainment, contribute to up to half of Alzheimer’s cases globally (17.2 million) and in the U.S. (2.9 million). Researchers projected that if a 10 to 25 percent reduction in all seven risk factors were to take place, it could potentially prevent as many as 1.1 to 3 million cases worldwide and 184,000 to 492,000 cases in the U.S.

Recognizing and addressing risk factors at a young age can greatly reduce the risk of developing dementia later in life. 

Lifestyle Changes to Promote Heart and Brain Health

What is good for your heart is good for your brain—making positive lifestyle changes that improve heart health can also improve brain health. It’s never too early or too late to make meaningful changes. Here’s what you can do to control vascular risk factors and promote brain health:

• Control your blood pressure and cholesterol.
• Eat a heart-healthy diet.
• Limit alcohol consumption.
• Stop smoking and avoid secondhand smoke.
• Stay active and exercise daily for 30 to 60 minutes.
• Get diabetes under control.
• Find ways to manage your stress.

Our brains are incredible and complex organs that control virtually every aspect of our existence, from how we process information to how we move, yet the brain is often looked at solely as the center of memory. This is why neurological diseases, like Alzheimer’s disease, are often perceived as diseases of memory. While memory is an important part of cognitive function and plays an essential role in our everyday lives, this is just one aspect of the brain’s functionality that neurological diseases impact.

The brain controls much more than just our memory; it controls both cognitive and functional aspects of our brain, meaning it controls how we think and move. Due to the high complexity of the brain, there are many different ways to categorize its functions. However, the functions are most commonly split into six categories. While this framework is not absolute, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines six key domains of cognitive function.

Below we detail each of these six key domains, how they play into how we assess brain health and diagnose neurological diseases, and how diagnosis and, consequently, patient treatment and care can be improved.

Defining the Six Key Domains of Cognitive Function

The DSM-5 defines six key domains of cognitive function: complex attention, executive function, learning and memory, language, perceptual-motor control, and social cognition. Below we provide simple explanations of each key domain.

Image courtesy of Jane S Paulsen

Complex Attention

Complex attention is our ability to focus on multiple things at once and our ability to choose what to pay attention to and what to ignore. We don’t think about it very often, but our capacity to remain focused, particularly when there are distractions and parallel tasks involved, requires significant effort from our brains.

Executive Function

Executive functions refer to high-level cognitive abilities required to control and coordinate other cognitive abilities and behaviors. In other words, these are the functions we need to plan, prioritize, make decisions, respond to our environments, and move between tasks. This includes all the sequencing, planning, and organization of sets of tasks. 

Learning and Memory

Learning and memory, which is the most well-known aspect of cognitive function, is our ability to record information, such as facts or events, and retrieve it when needed. Memory functioning is one of the most complex and multifaceted cognitive domains and is composed of many subdomains, including working memory, procedural memory, and prospective memory, among others.

Language

Language links strongly with our ability to communicate, whether through writing, reading, or speaking. Language abilities include things like naming objects, finding the right words, the fluidity and flow of our speech patterns, grammar and syntax, as well as receptive language.

Perceptual-Motor Control

Perceptual-motor control is our ability to coordinate our bodies’ movements in response to what is happening around us. In other words, it is our ability to interact with the environment around us by combining the use of our senses, like vision and touch, and motor skills.

Social Cognition

Social cognition is how we process, remember, and use information in social contexts to explain and predict our behavior as well as the behavior of others. This includes our ability to control our desires to act on impulses, express empathy, recognize social cues, read facial expressions, and motivate ourselves. 

The Role of Key Cognitive Domains in Neurological Disease Diagnosis

Several of these key domains of cognitive function are utilized in assessments to help diagnose neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, vascular dementia, and Lewy body dementia. Conventional neuropsychological assessments, such as the Mini-Mental State Exam and the Montreal Cognitive Assessment, aim to detect the presence of impairment to determine if further testing is needed. However, these assessments only assess aspects of cognition, meaning they do not adequately assess true neurocognitive (cognitive and functional) function.

Advancing Our Understanding of Neurocognitive Function to Improve Disease Diagnostics

While the DSM-5 categorizes cognitive function into six key domains, it is important to understand that there are both cognitive and functional domains that span across them, and each of the six key domains contains subdomains. To paint a true picture of neurocognitive function, it is important to assess a breadth of both cognitive and functional domains. With a more granular and accurate depiction of an individual’s neurocognitive function, early diagnosis and more personalized patient treatment and care can be achieved.

A comorbidity is an additional or secondary disease that an individual may have. Many individuals with Alzheimer’s and other causes of dementia are living with multiple comorbidities that are often underdiagnosed. 

In a population-based study from 2017, it was found that 91.8% of individuals living with dementia also have another health condition, with 13.2% having one condition, 33.8% having two or three conditions, 27.8% having four or five conditions, and 16.9% having six or more conditions.

Both clinical and molecular studies suggest that chronic diseases may be associated with an increased risk of Alzheimer’s disease in different populations. While the causes of disease comorbidities in Alzheimer’s are not yet fully understood, disruptions such as inflammation in several shared biological pathways have been proposed to be the underlying mechanism for this occurrence.

Below, we detail four common disease comorbidities in Alzheimer’s disease and the importance of early and frequent neurocognitive testing for individuals with diseases associated with an increased risk of developing Alzheimer’s disease.

Disease Comorbidities in Alzheimer’s

Disease comorbidities in Alzheimer’s disease significantly affect the clinical management of people living with Alzheimer’s. Many disease comorbidities in Alzheimer’s are associated with poor prognosis in those with Alzheimer’s. Identifying and addressing the presence of comorbid diseases early is critical for providing robust, personalized care and treatment.

Below, we outline four common disease comorbidities in Alzheimer’s disease.

Hearing Loss

Approximately 30% of adults aged 65 and older and 55% older than 80 years show some degree of hearing loss. The number of individuals impacted by age-related hearing loss is estimated to grow to 580 million worldwide by 2050.

In a study that tracked more than 600 adults for almost 12 years, researchers found that hearing loss correlated strongly with the development of dementia. Mild hearing loss doubled dementia risk, moderate hearing loss tripled the risk, and those with severe hearing impairment were five times more likely to develop dementia.

Vision Loss

In 2020, an estimated 596 million individuals worldwide were living with an untreated distance vision impairment, 43 million of whom were blind.

Recent studies have suggested there is an association between vision loss and cognitive impairment. While findings from recent studies are currently limited by sample size, their results suggest that visual impairment may be a risk factor for dementia. In a cohort study of 1,061 women, baseline visual impairment was associated with a two- to five-fold increased risk of developing dementia over a median 3.8 years of follow-up. More severe visual impairment was associated with an increasingly elevated risk of incident dementia. 

Diabetes

According to the World Health Organization, type 2 diabetes affects 422 million individuals worldwide and is the most prevalent metabolic disease. Type 2 diabetes is a well-established risk factor for Alzheimer’s disease, and the association between the two has been studied in depth. 

One 2019 study found that diabetes was associated with a 1.25 to 1.9-fold increase in cognitive impairment and dementia. Another 2019 study suggests that diabetes and prediabetes are associated with accelerated cognitive impairment.

Cardiovascular Disease 

Well-established links to the development of Alzheimer’s and other causes of dementia include cardiovascular diseases such as cerebrovascular disease as well as risk factors for cardiovascular diseases such as hypertension and diabetes. Cerebrovascular disease and Alzheimer’s disease share risk factors in addition to overlapping neuropathology.

One study found that elevated blood pressure in midlife was associated with the development of neuritic plaques and neurofibrillary tangles present in Alzheimer’s disease. Another study demonstrated that the use of antihypertensive drugs was associated with a lower incidence of Alzheimer’s disease.

Early and Frequent Neurocognitive Assessment to Drive Personalized Care

Hearing loss, vision loss, diabetes, hypertension, and cerebrovascular disease are widely prevalent diseases and conditions worldwide. As significant risk factors for developing Alzheimer’s-related dementia and other causes of dementia, individuals with these diseases must receive early and frequent neurocognitive testing. Early and frequent testing allows for the earliest possible identification of cognitive impairment, enabling early intervention and providing the ability to develop detailed, personalized care plans for those living with Alzheimer’s disease.

Historically, researchers, pharmaceutical companies, and healthcare providers alike have relied on conventional neuropsychological assessments like the Mini-Mental State Exam (MMSE) and Montreal Cognitive Assessment (MoCA) to gain insights into how an individual’s neurocognitive abilities may be changing over time. However, these assessments are subject to several biases, resulting in noisy, highly variable results.

While conventional neuropsychological assessments can provide a decent indication of overall neurocognitive function, they fail to provide the degree of data granularity, ecological validity, and infrastructure required to assess small, intraindividual changes in function longitudinally. This becomes particularly problematic for pharmaceutical companies working towards providing clear, objective evidence of drug efficacy in clinical trials for neurological diseases such as Alzheimer’s disease and Parkinson’s disease. 

Think about it like this—if you’re trying to prove a diet is effective in helping individuals lose weight, but the diet will only help someone lose five pounds and the scale you’re using always varies by +/- five pounds, you likely won’t get the evidence you’re seeking, regardless of the diet’s efficacy. The same idea applies to assessing drug efficacy in clinical trials. Without granular, accurate, and reliable data, there is no way to draw objective conclusions about the impact of the drug on clinical trial subjects.

Let’s take a deeper look into why conventional neuropsychological assessments are subject to bias and introduce an affordable yet accurate and reliable approach to assessing neurocognitive function in clinical trials.

Biases in Conventional Neuropsychological Assessments

Broadly speaking, there are two categories of biases that conventional neuropsychological assessments are subject to: administration and the assessment itself, as detailed below.

Administration Biases

Administration bias in neuropsychological assessments largely stems from the fact that the assessments require a human to coach the subject and administer and score the assessment. This introduces human-to-human bias and consequently, human-to-human variability. Additionally, these assessments must be performed in an office, introducing the risk of environmental bias and potentially influencing the results.

Assessment Biases

One of the most widely recognized challenges with conventional assessments lies in the assessments themselves. They are highly subject to education, age, language, and cultural biases. The lack of consideration of these biases and the inability to adequately adjust results accordingly makes clinical trials with diverse populations quite challenging.

The activities performed in conventional neuropsychological assessments are not ecologically valid and only exercise a narrow cross section of neurocognitive domains. Primarily, the assessments evaluate aspects of cognition as opposed to a breadth of cognitive and functional domains. In other words, normal day-to-day human variabilities within the test takers themselves can significantly bias the assessment results.

The Need for Better Neuropsychological Assessment Tools for Clinical Trials

In addition to metrics from conventional neuropsychological assessments, clinical trials often include aspects such as protein levels via scans and other procedures to assess drug efficacy—however, protein levels in the brain may not be the best indicator of whether or not subjects are improving. This further drives the need for better neuropsychological assessment tools in clinical trials. To reduce the risk of administration and assessment biases, assessments need to:

• Implement standardized instructions that are ideally delivered digitally without human intervention.
• Utilize computerized and automated scoring and reporting methods.
• Be designed in such a way that the neurocognitive evaluation matches and aligns with neurocognitive states required to complete Activities of Daily Living (ADLs).
• Exercise a breadth of both cognitive and functional domains.

With that said, assessing ADLs is arguably the most accurate and robust indicator of how a patient’s neurocognitive function is changing with drug or therapeutic intervention.

Over the last few decades, researchers have gained a much deeper understanding of Alzheimer’s disease, its pathology, and the underlying mechanisms of the disease. The growing knowledge of Alzheimer’s disease has paved the way for many promising avenues for treatments and therapies, creating a more robust and diverse pipeline of drugs to target a breadth of identified mechanisms. We have moved beyond treating the symptoms of Alzheimer's disease and are on the path to treating the disease at its core.

An incredibly promising Alzheimer’s research pipeline is emerging. Currently, there are 208 active Alzheimer’s clinical trials, including a whopping 118 trials evaluating disease-modifying therapies. However, pharmaceutical companies face many challenges and barriers that contribute to failed clinical trials. As much as 94.1% of drug-based neurological disease clinical trials fail—however, this doesn’t necessarily mean all of the failed drugs were ineffective. Many believe that failed drug-based neurological disease trials stem largely from unreliable data.

Let’s take a deeper look into pivotal clinical trials for Alzheimer’s disease drugs, common challenges with early-stage clinical trial drug development for Alzheimer’s disease, and how these challenges may be solved through a precision approach.

Pivotal Clinical Trials for Alzheimer’s Disease Drugs

Aducanumab (Aduhelm) was the first FDA-approved treatment for Alzheimer’s disease to enter the market since 2003 and is the first in the monoclonal antibody therapy class. Following the approval of Aducanumab, several other emerging amyloid-related therapies are beginning to be pushed forward. Biogen and Eisai’s treatment, Lecanebab, and Eli Lilly and Company’s treatment, Donanemab, both received the FDA’s Breakthrough Therapy designation for the treatment of Alzheimer’s.

According to the Alzheimer’s Drug Discovery Foundation’s 2021 Alzheimer’s clinical trial report, a vast range of targets, as well as a growing list of therapy types, are currently in the pipeline, and 77% of the 118 disease-modifying trials have novel targets other than amyloid or tau. New targets in disease-modifying therapies include neuroprotection, inflammation, mitochondria and metabolic dysfunction, vascular disease, synaptic activity and neurotransmitters, and genetics and epigenetics. 

The wide range of targets opens the door to a more precise, personalized approach to treating Alzheimer’s disease. Every individual’s neurocognitive domain functions are affected uniquely in the presence of Alzheimer’s, meaning the treatment pathways will also likely be unique. Utilizing multiple effective treatments personalized to an individual’s unique impairments will allow for more individualized and more effective treatment and care.

Challenges in Early Stage Clinical Trial Drug Development for Alzheimer’s Disease

While the potential of emerging drugs and therapies for Alzheimer’s disease progresses rapidly, diagnostics tools and methods for robust monitoring of neurocognitive function for clinical trials remain rather outdated, driving subject recruitment costs through the roof, prolonging timelines for early-stage clinical trial drug development for Alzheimer’s, and contributing to clinical trial failures. Common challenges in early-stage clinical trial drug development for Alzheimer’s disease occur during subject selection and longitudinal monitoring of neurocognitive changes within subjects.

Screening and Subject Selection

Subject screening and recruitment for clinical trials for Alzheimer’s disease is currently very cost-inefficient due to a lack of precision diagnosis. To determine subject eligibility, many early-stage Alzheimer’s drug clinical trials require expensive positron emission (PET) scans or invasive cerebrospinal fluid analyses as a part of the key inclusion criteria to establish protein levels, such as beta-amyloid and tau. As there can be hundreds or even thousands of potential subjects, the screening and selection process can skyrocket clinical trial expenses. 

Unfortunately, costly imaging and diagnostic procedures have been the standard for this process, as there has been a lack of reliable measurement tools available to understand precisely where potential subjects lie on a disease continuum, meaning pharmaceutical companies lack tools to narrow the subject pool before completing hundreds or thousands of costly PET scans.

Longitudinal Monitoring of Neurocognitive Changes within Subjects

Expensive imaging techniques, such as PET scans and magnetic resonance imaging, used to visualize changes within the brain are also commonly utilized as a primary outcome to assess drug efficacy. However, protein levels in the brain, for example, may not be the best indicator of whether or not an Alzheimer’s subject has improved. Neither brain imaging nor traditional neurocognitive assessments have the data granularity or ecological validity to truly understand a drug’s impact on the subject’s true brain function and ability to complete Activities of Daily Living (ADLs).

The way we view the prevention, diagnosis, and treatment of neurocognitive diseases like Alzheimer’s disease and other causes of dementia is continuously evolving, promoting a shift from a reactive to a proactive preventive approach in healthcare. While much of the research surrounding dementia has been focused on potential treatments and therapies, a significant amount of research has been dedicated to understanding the pathogenesis of disease development.

Research has revealed there is a connection between mood disorders like depression and the development and progression of dementia, giving rise to promising methods to prevent and even treat dementia. However, people can often become confused about this connection and what it means for them. Some people living with depression are worried they will inevitably develop dementia and are asking their doctors if depression can be a precursor to dementia.

To clear up any confusion, let’s take a look at the connection between depression and dementia, the risk factors involved in the development and progression of dementia, and the importance of early neurocognitive testing for those with mental health issues.

Can Depression Be a Precursor to Dementia?

It’s important to note that depression does not directly cause dementia—rather, depression may contribute to other risk factors known to increase the risk of developing dementia. In other words, depression can be a precursor to dementia, but not in the way you may think. It appears that depression and its associated lifestyle impacts may be a modifiable risk factor for Alzheimer’s disease and other causes of dementia. 

Research studies continue to demonstrate the significant association between depression symptoms and dementia. One study suggests that depression symptoms before the onset of Alzheimer’s disease are associated with the pathogenesis of Alzheimer’s, even when the first depression symptoms occurred more than 25 years before the onset of Alzheimer’s. This indicates that depression symptoms are a risk factor for the future development of Alzheimer’s.

There is a clear link between depression and dementia, but the main connection lies between the symptoms of depression and dementia. Depression symptoms, such as social isolation and lack of stimulation, have been recognized as modifiable risk factors for dementia.

Social Isolation and Lack of Stimulation as Risk Factors for Dementia

Social isolation, social withdrawal, and lack of mental and social stimulation are common lifestyle impacts that often accompany depression. 

Several studies suggest that maintaining social and mental activity throughout life may support brain health and decrease the risk of developing dementia. Meta-analyses found that social isolation or loneliness in older adults is associated with a 50% increased risk of developing dementia.

In addition to the evidence of this connection in research, emerging theories suggest that social and neurocognitive stimulation can help build up your “cognitive reserve,” where cognitive reserve refers to your brain’s ability to efficiently use networks of neuron-to-neuron connections. This enables individuals to effectively execute neurocognitive tasks, even as the brain changes over time.

Other Risk Factors Involved in the Development of Dementia

The pathology of dementia is complex. Many causes of dementia are multifactorial, meaning they are not caused by a single factor, but rather develop from some combination of several factors, such as genetics, environment, and lifestyle.

The Lancet Commission on Dementia prevention, intervention, and care identified 12 potentially modifiable risk factors that account for approximately 40% of worldwide dementias.

The Importance of Early Neurocognitive Testing

Like many other diseases and disorders, early intervention and early treatment are likely to produce better health outcomes. Early testing and monitoring of neurocognitive brain health are critical for the early identification of impairment and early intervention for all individuals, but particularly for those with risk factors like depression and other mental health issues. 

It is never too early to understand and monitor your brain health. It is a vital part of overall wellness and plays a key role in our ability to live long, healthy, and full lives.