Experts estimate that up to 40% of people living with Alzheimer’s disease suffer from significant depression. Mental health conditions commonly coexist in people living with cognitive disorders such as Alzheimer’s disease and Parkinson’s disease, but the connection appears to be even stronger than this.

Let’s take a closer look at the link between cognitive disorders and mental health and methods for better patient care and support.

The Link Between Cognitive Disorders and Mental Health

Depression—as well as the isolation and reduced mental and social activity that often accompany depression—appears to be a risk factor for developing several cognitive disorders. On the other hand, cognitive and neurological impairments can be present in many mental illnesses.

Depression as a Risk Factor for Alzheimer’s and Parkinson’s Disease

It is widely recognized that the onset of Alzheimer’s and other causes of dementia may be modifiable through the management of risk factors and incorporation of lifestyle changes. It appears that depression and its associated lifestyle impacts may be a modifiable risk factor for Alzheimer’s disease. 

Studies continue to demonstrate the significant association between depression symptoms and Alzheimer’s disease. 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. 

Similar to Alzheimer’s disease, depression is more common in individuals with Parkinson’s disease than in the general population. It’s believed that depression is either a causal risk factor for Parkinson’s or may be a very early prodromal symptom of Parkinson’s.

Cognitive Impairment in Mood Disorders

The link between cognitive disorders and mental health is also demonstrated by the presence of cognitive impairments in several mood disorders. 

Cognitive deficits in mood disorders have been studied at length, and impairments across several cognitive domains, including attention, executive function, and recall memory, have been observed in mood disorders.

One study comparing depressed and euthymic individuals with healthy controls found that euthymic individuals did not show signs of significant impairment in the domain of attention and working memory, while depressed and manic individuals in the acute phases of their illnesses produced more errors of attention in comparison to matched controls. Increased severity of mental illness correlated with larger cognitive performance deficits. 

They also found that when compared with healthy controls, those with euthymic bipolar I showed executive functioning impairment while acutely ill, with improvements when retested during subacute phases.

The study also revealed that individuals who were acutely depressed showed signs of nonverbal memory impairment, while the nonverbal memory of euthymic individuals was similar to that of the control group.

Methods for Better Patient Care and Support

There is a clear connection between cognitive disorders and mental health—but how does this impact our approach to providing better support to patients? 

Cognitive disorder prevention and treatment lies in the early detection of cognitive impairment. Additionally, the assessment and management of cognitive impairments in mood disorders are important for providing optimal treatment.

We are experiencing a shift in the world of healthcare towards a more personalized, holistic approach to medicine. When paired with mental health screening and patient monitoring, regular cognitive testing allows providers to understand the cognitive and mental states of their patients and rapidly inform care when changes are detected, providing the opportunity for early intervention and better health outcomes.

Understanding dementia’s impact on Activities of Daily Living (ADLs) is critical for informing providers, caregivers, and families on how to best care for and support dementia patients. 

Impairments in Activities of Daily Living, including the ability to complete basic ADLs such as eating, bathing, and dressing, accompany the cognitive, functional, and behavioral changes in dementia patients.

Below we detail several aspects of dementia’s impact on neurocognitive function, traditional methods for assessing dementia’s impact on Activities of Daily Living, their limitations, and how to bridge the gap to better patient care and support.

Dementia’s Impact on Activities of Daily Living

There are several cognitive and functional aspects of brain function that can hinder a patient’s ability to perform Activities of Daily Living, including executive functioning, memory, judgment, attention, and spatial memory.

Executive Functioning

Executive functioning refers to the high-level cognitive abilities required to control and coordinate other cognitive abilities and behaviors. The executive functioning of dementia patients can be affected in a number of ways, including in the ability to pay attention, organize and prioritize, focus on tasks, and self-monitor. Dementia patients often struggle with sequencing, planning, and organizing a set of tasks. For example, this may become apparent when performing multi-step activities such as washing their hair or getting dressed.

Memory 

Many dementia patients, particularly in the later stages, experience memory loss. Symptoms of memory loss may include forgetting recently learned information, repeating the same question, and forgetting birthdays or other important dates and events and being unable to remember them later. Patients with memory loss may also struggle with remembering to change into clean clothes in the morning or brush their teeth and hair.

Judgment

Judgment and decision-making skills are often impacted in dementia patients, as the parts of the brain involved in remembering, understanding, and processing information may be affected. Dementia patients may make inappropriate decisions such as wearing shorts and a t-shirt when it’s snowing outside, giving away money, or deciding that bathing is unnecessary.

Attention

Dementia patients may become easily distracted, struggle with concentrating, or have a short attention span, potentially impacting their ability to complete normal tasks. This may make starting and completing tasks like dressing, bathing, or eating more difficult.

Spatial Memory

Spatial memory is the ability to recall the locations of objects, places, or events. A patient in the early stages of dementia may forget where they placed objects in their environment and may even place objects in abnormal locations. When looking for misplaced objects, patients may have difficulty retracing their steps.

Traditional Methods for Assessing Dementia’s Impact on Activities of Daily Living

To assess a dementia patient’s ability to perform Activities of Daily Living, the Alzheimer’s Association recommends the use of the Katz ADL and Lawton-Brody Instrumental ADL (IADL). Both assessments aim to assess a patient’s ability to perform Activities of Daily Living or tasks necessary to live independently in a community. 

The Katz ADL is typically administered by a caregiver and assesses the following activities:

• Bathing
• Dressing
• Toileting
• Transferring
• Continence
• Feeding

The Lawton-Brody IADL is similar but is considered to assess Activities of Daily Living of higher complexity by evaluating the following activities:

• Ability to Use Telephone
• Shopping
• Food Preparation
• Housekeeping
• Laundry
• Mode of Transportation
• Responsibility for Own Medications
• Ability to Handle Finances

While both assessments can provide a decent understanding of a patient’s function, they may not be sensitive to small, incremental, intra-individual change—in other words, they don’t sufficiently capture enough detail to ensure the patient is receiving proper care and support for their current neurocognitive functioning abilities.

Additionally, assessing a patient's ability to complete the six to eight types of activities through a demonstration of each task is very time-consuming and can often lead to self-reporting or surrogate reporting methods, resulting in significant inaccuracies such as the overestimation or underestimation of functional abilities. Due to the administrative needs of these assessments, it becomes difficult to assess the abilities of patients regularly, which is necessary to effectively update care plans and evaluate the changing needs of patients.

Simulating Activities of Daily Living to Drive Better Patient Care and Support

Assessing the changes in a patient's ability to complete ADLs longitudinally at a granular level is arguably the best measure of how a dementia patient’s brain and abilities are changing over time; however, this is often not feasible through traditional assessments.

According to the Alzheimer’s Association, in 2021, Alzheimer’s disease and other forms of dementia will cost the nation $355 billion, including $239 billion in Medicare and Medicaid payments combined. Without reliable, accessible, and cost-efficient cognitive function assessment tools to provide early diagnosis and treatments to slow, stop, or prevent Alzheimer’s, the projected cost from Alzheimer’s alone is projected to reach $1.1 trillion in 2050.

The prevention and treatment of neurological diseases, including Alzheimer’s, depends heavily on early detection, but historically, there has been a lack of proper diagnostic tools. The limitations of existing cognitive and functional assessments have led to inadequate cognitive screening in older adults. Only half of all seniors are being assessed for cognitive impairment, and only one in seven seniors are receiving regular brief cognitive assessments.

Below we detail the need to refine cognitive function assessment tools, the limitations of traditional tools, and the shift towards multimodal assessments.

The Need to Refine Cognitive Function Assessment Tools

There is an overwhelming need to refine cognitive function assessment tools to better support physicians in their efforts to detect cognitive and functional impairment before the clinical onset of neurological diseases. Early detection means early intervention and treatment, which ultimately leads to better health outcomes.

An immense amount of research has expanded our understanding of neurological diseases like Alzheimer’s disease and Parkinson's disease, providing a better understanding of disease signatures, yet providers are still left with tools that are outdated, narrow, and produce highly variable results.

Limitations of Traditional Cognitive Function Assessment Tools

Traditional cognitive function assessment tools have a multitude of limitations that may be contributing factors to the inadequate cognitive screening of older adults. Limitations and challenges include the following:

• Administration challenges: A healthcare professional is required to administer and interpret the results of traditional assessments, introducing the risk of bias or human-to-human variability as well as prolonging diagnostic timelines.
• Lack of ecological validity: Traditional cognitive function assessment tools are not ecologically valid, meaning the design of the evaluation does not match and align with neurocognitive states representative of Activities of Daily Living (ADLs).
• Language bias: Tools like the Mini-Mental State Exam (MMSE) and Montreal Cognitive Assessment (MoCA) are highly variable from one subject to another, as they introduce language and cultural bias. 
• The ceiling effect: The ceiling effect present in assessments such as the MMSE and MoCA can cause highly educated impaired individuals to score high, thus overestimating their neurocognitive abilities and contributing to missed diagnoses.
• Variable results: Results from traditional assessments become even more variable beyond language, education, and cultural bias, as the patient’s performance is highly subject to their “good” and “bad” days.

A Shift Towards Multimodal Assessments

Within our industry, we are beginning to see a shift towards multimodal assessments. Multimodal neurocognitive assessments that require patients to use more than one modality are the future of truly assessing their abilities to complete complex ADLs. 

By requiring patients to complete tasks while using multiple modalities such as visual, auditory, and spatial to track aspects like eye movement, speech, and gait, we can paint a full and detailed picture of a patient’s true neurocognitive abilities. This will allow providers to detect signs of cognitive or functional impairments early on, before the clinical onset of neurological disease symptoms.

Have you ever had an instinctual sense about something that seemed to originate from your gut, or have you ever felt butterflies in your stomach? These feelings indicate that your brain and gut are connected.

Concealed within the walls of your digestive system is your enteric nervous system, or your “second brain.” Your brain and gut communicate with each other through a system called the gut-brain axis. This knowledge is transforming our perception of the connections between gut health and several aspects of overall health, such as brain function, the immune system, and mood.

Disturbances along the gut-brain axis may heavily contribute to the pathogenesis, or manner of disease development, of many neurodegenerative diseases, such as Alzheimer’s disease. This not only deepens our understanding of Alzheimer’s disease but also provides a potential avenue for novel therapeutic approaches.

Let’s explore the link between the gut-brain health connection and Alzheimer’s disease as well as how this concept may pave the way to future Alzheimer’s treatments.

Understanding the Gut-Brain Health Connection

The gut microbiome is the collection of microorganisms living in your digestive tract, including bacteria, archaea, viruses, and fungi. Researchers have discovered that the gut microbiome and the brain communicate with each other bidirectionally. In other words, your gut microbiome can affect brain functions, and brain functions can affect your microbiome.

In vitro, in vivo, and human studies found links between changes in the gut microbiome and functional changes in the brain. This suggests that the microbiome impacts aspects such as stress, anxiety, depression, and cognitive function.

Based on the concept that the gut microbiome and cognitive function are connected, studies are being conducted that specifically assess how the gut-brain health connection and Alzheimer’s disease may be linked.

The Gut-Brain Health Connection and Alzheimer’s Disease

The gut-brain axis involves pathways, such as metabolic, immune, endocrine, and neural, that are essential for maintaining brain homeostasis. It’s believed that gut dysbiosis plays a part in the development of Alzheimer’s disease and other conditions such as cardiovascular disease and type 2 diabetes mellitus. Gut dysbiosis refers to abnormal changes and reductions in microbial diversity in the composition of microorganisms living in the digestive tract.

An increasing amount of experimental and clinical data confirms that gut dysbiosis plays a key role in neurodegeneration. More specifically, in Alzheimer’s disease, gut dysbiosis may promote beta-amyloid aggregation, neuroinflammation, and oxidative stress, all of which contribute to the development of Alzheimer’s disease. Simply put, dysregulation of the gut microbiome causes imbalances in the community of microorganisms in the gastrointestinal tract.

Additionally, alterations in the gut microbiome composition may lead to increased permeability of the gut barrier and immune activation, causing systemic inflammation. This inflammation may impair the blood-brain barrier, thereby promoting neuroinflammation and neural injury. This can ultimately lead to neurodegeneration.

This new understanding of the gut-brain health connection and Alzheimer’s disease may pave the way to future therapeutic approaches.

Potential Novel Therapeutic Approaches

With the understanding that alternations in the gut microbiome contribute to the pathogenesis of Alzheimer’s disease, researchers are beginning to explore potential novel therapeutic approaches.

The relationship between the gut microbiome in the development of Alzheimer’s and gut dysbiosis, increased permeability of the gut barrier, and neurological dysfunction may pave the way for new interventions. Potential therapeutic approaches include:

• Probiotic supplementation to protect against disruption of the gut barrier, reducing systemic inflammation and preventing neuroinflammation and neurodegeneration.
• Antibiotic treatment to treat small intestinal bacterial overgrowth and intestinal colonization by pathogenic strains.
• Fecal microbiota transplantation to restore gut microbiome diversity and stability.
• Dietary intervention to modulate the gut microbiome.

When implementing changes with your physician with the intent to improve your gut-brain health, you will need a way to measure how your brain health is improving or changing over time in a quantifiable manner. 

6.5 million Americans aged 65 and older are living with Alzheimer’s disease, and this number continues to grow, with 12.7 million people aged 65 and older projected to have Alzheimer’s disease by 2050 unless there are medical breakthroughs to prevent, slow the progression of, or cure Alzheimer’s disease.

Can healthy living prevent Alzheimer’s disease? While there are currently no proven strategies to prevent Alzheimer’s, strong evidence from developing research suggests that several factors of healthy living may significantly reduce the risk of developing the disease. 

Let’s take a look into how healthy living may prevent Alzheimer’s disease and actionable steps you can take to reduce the risk of developing Alzheimer’s.

Evidence Suggesting Healthy Living Can Prevent Alzheimer’s Disease 

Researchers reviewed data from two memory and aging longitudinal studies, selecting participants with data on their diets, lifestyle factors, genetics, and clinical assessments. Each of the 1,845 participants was scored based on five factors of healthy living, including the following:

• ≥ 150 minutes of moderate- to vigorous-intensity physical activity per week
• Refraining from smoking
• Light-to-moderate alcohol consumption
• Incorporation of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which is a combination of the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diet
• Engagement in late-life cognitive activities

When compared to participants with zero or one of the above lifestyle factors, the risk of developing Alzheimer’s was 37% lower in participants with two or three of the above lifestyle factors and a whopping 60% lower in participants with four or five of the above lifestyle factors.

Incorporating Lifestyle Changes to Prevent Alzheimer’s Disease

As indicated above, factors that can reduce the risk of developing Alzheimer’s disease include quitting smoking, controlling alcohol consumption, eating a healthy diet, increasing physical activity, and getting sufficient mental engagement. Other factors that may reduce the risk include protecting the brain from head trauma and protecting the ears from hearing loss. Let’s delve a little deeper into actionable steps you can take to improve brain health. 

Controlling Cardiovascular Risk Factors

Many factors of healthy living relate to a concept called the heart-head connection, meaning what is good for the heart is good for the head. Many conditions that increase the risk of cardiovascular disease also increase the risk of developing Alzheimer’s disease.

Conditions such as high cholesterol, high blood pressure, and diabetes are known to increase the risk of cardiovascular disease and thus may also increase the risk of developing Alzheimer’s.

To control cardiovascular risk factors, experts recommend the following:

• Smoking cessation: As soon as a day after quitting smoking, your risk of heart disease is reduced significantly. Cigarette smoke reduces the amount of oxygen in your blood, which in turn forces your heart to work harder and increases your blood pressure and heart rates. The chemicals in tobacco may also directly damage your blood vessels and heart.
• Controlling alcohol consumption: In addition to liver damage, the excessive consumption of alcohol can lead to several heart conditions such as high blood pressure while increasing the risk of stroke, heart attack, and arrhythmias. Light-to-moderate alcohol consumption is no more than two drinks per day for men and no more than one drink per day for women.
• Eating a healthy diet: Heart-healthy diets, such as the Mediterranean diet, the DASH diet, and the MIND diet, can protect your heart, reduce your risk of type 2 diabetes, and improve your blood pressure and cholesterol levels. These diets typically include an increased intake of fruits and vegetables, legumes, whole grains, nuts and seeds, and healthy fats such as olive oil and a reduced intake of sugar, processed carbohydrates, and saturated fats.
• Exercising daily for 30-60 minutes: Regular physical activity helps maintain a healthy weight and reduces the risk of cardiovascular conditions, including high blood pressure and high cholesterol.

Other Factors That May Contribute to the Development of Alzheimer’s 

Research suggests that there is a strong correlation between serious head trauma and cognitive decline. One study suggests that sustaining a moderate head injury doubles the risk of developing Alzheimer’s disease as well as other causes of dementia. While some head injuries can’t be prevented, you can take steps to avoid certain cases. For example, you can reduce the risk of head injury by taking precautions such as wearing your seatbelt or using a helmet when participating in sports.

A newly discussed factor that may contribute to developing dementias such as Alzheimer’s is hearing loss. 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.

While the specific mechanism connecting hearing loss to neurodegeneration is not yet clear, one contributing factor may be the social isolation that often comes with hearing loss. Several neurobiological changes associated with faster cognitive decline are connected to a lack of social and mental engagement.

Alzheimer’s disease is the most common cause of dementia. More than six million Americans are living with Alzheimer’s disease, and as of 2022, one in nine people aged 65 and older have been diagnosed.

Historically, Alzheimer’s has been a devastating disease, but the tides are turning. Research focused on prevention, early detection, and treatment continues to pave the way to a whole new outlook on Alzheimer’s and other neurological diseases. 

Similar to many other diseases, when Alzheimer’s disease is diagnosed early, treatment may be more effective and produce better health outcomes. Understanding and monitoring your brain health as early as possible is key to the early detection of Alzheimer’s disease.

Below we explain eight early signs of Alzheimer’s disease in young adults as well as advancements in brain health monitoring and early Alzheimer’s disease detection.

8 Early Signs of Alzheimer’s Disease in Young Adults

Aging is a natural process of human life. As we age, we experience subtle and gradual changes in our bodies and brains; however, it is important to understand which changes in your brain are not caused by normal aging. Some of these changes may be early signs of Alzheimer’s disease or other causes of dementia. Here are some of the most common early signs of Alzheimer’s disease in young adults.

1. Memory Loss

While we all have occasional memory lapses, memory loss that interferes with or disrupts your daily life is one of the most common early signs of Alzheimer’s. Signs of memory loss may include forgetting recently learned information, repeating the same question, and forgetting birthdays or other important dates and events and being unable to remember them later.

2. Difficulty with Planning or Performing Familiar Tasks

Planning is our ability to think about what tasks are required to accomplish a specific goal. Difficulties with planning may include forgetting the rules and steps to a favorite game or struggling with planning and cooking a familiar recipe or driving to a familiar place.

3. Challenges with Problem-Solving

Some people who are in the early stages of Alzheimer’s disease may have difficulty solving problems or working with numbers. This could mean taking longer to complete familiar tasks or having difficulty concentrating on the task at hand.

4. Difficulty Understanding Time or Place

We have all occasionally forgotten what day of the week it is, but regularly forgetting the date or being confused about the passage of time may be an early sign of Alzheimer’s disease. Those in the early stages of Alzheimer’s may also forget their location or how they ended up there.

5. Changes in Visual Perception

Changes in vision and visual perception are one of the least-discussed signs of Alzheimer’s. Some individuals may struggle with visualizing and interpreting their surroundings. They may have difficulty judging distances and experience challenges while driving.

6. Poor Spatial Memory

Spatial memory is our ability to recall the location of objects, places, or events. Someone in the early stages of Alzheimer’s may forget where they placed objects in their house or environment and may even place them in abnormal locations. They may also struggle to retrace their steps to find the lost object.

7. Changes in Mood

Those with Alzheimer’s disease may begin to experience a shift in mood or changes in their personality. In the early and middle stages of Alzheimer’s, many individuals struggle with depression. They may also experience mood swings, confusion, irritability, anxiety, or may withdraw from their normal social activities.

8. Changes in Speech 

In the early stages, individuals with Alzheimer’s may experience changes in speech, such as difficulty recalling words or finding the right word to use, pausing while speaking, or struggling to finish a sentence.

The Importance of Early, Frequent Cognitive Testing

While it is important to understand visible symptoms and early signs of Alzheimer’s disease in young adults, the ability to provide early detection and diagnosis depends on detecting Alzheimer’s disease before the onset of noticeable symptoms.

Early detection in the pre-symptomatic phases begins with regular and frequent measurement and monitoring of brain health as early as possible to identify impairment and assess the risk of disease development.

When assessing the efficacy of a drug for neurological diseases, such as Alzheimer’s disease and Parkinson’s disease, pharmaceutical companies face several challenges with subject recruitment and the ability to get drugs to market. These challenges often result from a lack of reliable, accessible, and affordable tools for screening, subject selection, and longitudinal monitoring.

Below, we look into common clinical trial challenges, measurement scales and scoring systems for neurocognitive assessments and their limitations, and how clinical trials for neurological diseases can be streamlined.

Common Challenges in Clinical Trials

Subject recruitment for clinical trials for neurological diseases can be extremely costly. Take Alzheimer’s disease, for example—to determine subject eligibility, many Alzheimer’s clinical trials require positron emission (PET) scans as a part of the key inclusion criteria to establish protein levels, such as beta-amyloid and tau. As there can be hundreds of potential candidates, this process can cost hundreds of thousands of dollars. Historically, there has been a lack of reliable measurement tools available to narrow down the subject pool before completing hundreds of costly PET scans.

PET imaging looks for reduced beta-amyloid protein levels in the brain and is frequently utilized as a primary outcome to determine drug efficacy. However, protein levels in the brain may not be the best indicator of whether or not an Alzheimer’s subject has improved because it isn’t clear if the development and progression of beta-amyloid plaques correlate with neurocognitive decline. Neither brain imaging nor traditional neurocognitive assessments can determine the impact of the drug on the subject’s ability to function and complete Activities of Daily Living (ADLs).

Limitations of Measurement Scales and Scoring Systems for Neurocognitive Assessments

Measurement scales and scoring systems for neurocognitive assessments, such as the Mini-Mental State Exam (MMSE) and Montreal Cognitive Assessment (MoCA), are quite limited in providing meaningful measures of neurocognitive abilities. The MMSE and MoCA are both scored on a single 30-point scale, meaning they only provide a single macro-level score and low granularity analog data. 

Perhaps the biggest limitations of measurement scales and scoring systems for neurocognitive assessments are their narrowness and lack of ecological validity, or the concept of realism with which the design of neurocognitive evaluation matches and aligns with neurocognitive states required to complete ADLs.

Other limiting factors of measurement scales and scoring systems for neurocognitive assessments include the following:

• Measurement scales and scores for MMSE and MoCA only reflect a subject’s neurocognitive abilities by looking at measures such as task completion time, success, and accuracy.
• The MMSE and MoCA are highly subject to a subject’s “good” and “bad” days, which can result in variable results.
• The MMSE and MoCA require a healthcare professional to administer and interpret assessment results, introducing the risk of bias or human-to-human variability.
• Scoring of the MMSE and MoCA is highly variable from one subject to another, as they introduce education, age, language, and cultural bias. 
• The ceiling effect present with MMSE and MoCA can cause highly educated, impaired individuals to score high, thus overestimating their neurocognitive abilities.

Streamlining Clinical Trial Recruitment

The ability to simulate complex ADLs and collect highly granular data measuring a wide range of neurocognitive abilities across many domains can streamline clinical trial recruitment as well as act as a novel metric throughout clinical trials to assess drug efficacy.

The simulation of ADLs can be used as an assessment during subject recruitment to make an initial eligibility determination for the large population of potential candidates, thus narrowing the eligible subject pool. From here, the subset of subjects can receive a PET scan to confirm candidate eligibility, saving thousands of dollars on PET scans.