The Latest Advances in Treating Major Neurocognitive Disorder

What is major neurocognitive disorder?

Major Neurocognitive Disorder (NCD), also known as dementia, is a condition marked by a significant decline in cognitive functioning that impairs daily activities and independent living. The term “Major Neurocognitive Disorder” was first used in the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) to describe a wide range of cognitive impairments, including Alzheimer’s disease, vascular dementia, frontotemporal dementia, and Lewy body dementia, among others.

People with Major NCD have problems with memory, executive function, language, attention, and social cognition. As the disease progresses, cognitive deficits can make it difficult to perform basic daily tasks like money management, cooking, and personal hygiene. Major NCDs are most commonly diagnosed in older adults, with age being the primary risk factor, but they can also occur in younger people due to genetic factors, traumatic brain injury, or neurodegenerative diseases.

The underlying causes of Major NCDs vary. The most common cause is Alzheimer’s disease, which causes the brain to accumulate amyloid plaques and tau tangles. Vascular dementia is caused by a reduction in blood flow to the brain as a result of a stroke or chronic cardiovascular disease. Despite the disorder’s complexity and variability, advances in research are paving the way for novel treatment strategies aimed at slowing cognitive decline and improving quality of life for people with Major NCD.

Traditional Treatments for Major Neurocognitive Disorder

Traditionally, the treatment of Major Neurocognitive Disorder has been multifaceted, with emphasis on pharmacological interventions, behavioral therapies, and lifestyle changes. The primary goal of these treatments is to reduce symptoms, slow the progression of cognitive decline, and improve the patient’s ability to remain independent for as long as possible. Here’s a detailed look at the established methods for treating Major NCD.

1. Pharmacological Treatment

Pharmacotherapy remains a cornerstone in the treatment of Major NCD, especially for people with Alzheimer’s disease and related dementias. The medications used are divided into two categories: cholinesterase inhibitors and NMDA receptor antagonists.

• Cholinesterase Inhibitors: These medications are frequently prescribed to people in the early to moderate stages of Alzheimer’s disease. They work by preventing the breakdown of acetylcholine, a neurotransmitter that is essential for learning and memory. Increasing acetylcholine levels in the brain can help to stabilize or improve cognitive function. Some of the most commonly prescribed cholinesterase inhibitors are:
• Donepezil (Aricept): Approved for all stages of Alzheimer’s, donepezil has been shown to slow cognitive decline in some patients while also improving daily functioning and behavior.
• Rivastigmine (Exelon): Available as a pill or patch, rivastigmine is used to treat mild to moderate dementia caused by Alzheimer’s and Parkinson’s disease.
• Galantamine (Razadyne): Typically used in the mild to moderate stages of Alzheimer’s, galantamine improves nerve cell communication by increasing acetylcholine levels.
• NMDA Receptor Antagonists: These medications regulate the activity of glutamate, a neurotransmitter that, in excess, can cause neurodegeneration. The best-known drug in this category is:
• Memantine (Namenda): Memantine is approved for moderate to severe Alzheimer’s disease and is frequently used in conjunction with cholinesterase inhibitors. It assists patients with advanced dementia in maintaining their ability to perform simple tasks such as dressing and bathing.

While these medications can provide symptom relief, they do not cure Major NCD or slow its progression. The benefits are typically modest, and some people may experience side effects such as nausea, diarrhea, or dizziness.

2. Behavioral and Cognitive Therapy

Behavioral interventions are essential in managing the cognitive and psychological symptoms associated with Major NCD. These therapies are designed to help patients maintain cognitive function as long as possible while also addressing mood-related symptoms such as depression, anxiety, and aggression.

• Cognitive Stimulation Therapy (CST) is a structured program in which patients participate in mentally stimulating activities such as puzzles, discussions, and memory exercises. CST has been shown to improve cognitive function, specifically memory, language, and executive function. It can also improve one’s mood and overall well-being.
• Reminiscence Therapy: This type of therapy encourages patients to recall past events, usually through the use of photographs, music, or personal mementos. Reminiscence therapy can help dementia patients strengthen emotional connections, boost self-esteem, and relieve depression symptoms.
• Reality Orientation Therapy: This intervention helps patients stay oriented to their surroundings by reinforcing basic information like the date, time, and location. Reality orientation therapy is frequently used in conjunction with environmental cues, such as calendars, clocks, and personalized signs, to foster familiarity and reduce confusion.

3. Lifestyle modifications

Several lifestyle changes can help slow cognitive decline and improve overall brain health in people with Major NCD. These changes promote cardiovascular health, reduce inflammation, and improve cognitive reserve.

• Physical Activity: Regular exercise is one of the most effective non-pharmacological ways to slow cognitive decline. Aerobic exercise, such as walking, swimming, or cycling, has been shown to increase blood flow to the brain, reduce inflammation, and promote the growth of new neurons.
• Diet: The Mediterranean diet, which includes fruits, vegetables, whole grains, and healthy fats, has been linked to a lower risk of developing dementia. Foods high in antioxidants, such as berries and leafy greens, can help protect the brain from oxidative stress, whereas omega-3 fatty acids found in fish can reduce inflammation and improve cognitive function.
• Social Engagement: Maintaining strong social connections is critical to brain health. Social isolation has been linked to accelerated cognitive decline, whereas meaningful social interactions can stimulate the brain and improve mental health.
• Cognitive Training: Activities that challenge the brain, such as crossword puzzles, reading, or learning new skills, can improve cognitive reserve and delay the onset of symptoms in people at risk of dementia.

4. Environmental adaptations

Creating a supportive environment, in addition to pharmacological and lifestyle interventions, is essential for managing Major NCD. Modifications in the home or care facility can help reduce confusion, improve safety, and foster independence.

• Memory Aids: Using memory aids like labeled drawers, visual cues, and reminder systems can help people with dementia keep their daily routines and reduce frustration.
• Safety Measures: Installing grab bars in the bathroom, eliminating tripping hazards, and providing adequate lighting can help prevent falls and injuries in people with cognitive impairments.
• Routine and Structure: Having a consistent daily routine for meals, medications, and activities can help people with Major NCD feel more secure.

New Innovations in Major Neurocognitive Disorder Treatment

Advances in neuroscience, pharmacology, and technology are changing the treatment options for Major Neurocognitive Disorder. These innovations provide new hope for patients and caregivers, as they have the potential to not only alleviate symptoms but also change the underlying disease process. The following are some of the most promising advances in the treatment of major NCDs.

1. Monoclonal Antibodies and Amyloid Targeted Therapies

One of the most significant breakthroughs in Alzheimer’s disease research has been the development of monoclonal antibodies that target amyloid-beta plaques, which are thought to play an important role in disease progression.

• Aducanumab (Aduhelm): The FDA approved aducanumab in 2021 as the first disease-modifying therapy for Alzheimer’s disease. It works by binding to amyloid-beta plaques in the brain, allowing the immune system to eliminate these harmful proteins. Clinical trials have demonstrated that aducanumab can reduce the accumulation of amyloid plaques, potentially slowing the progression of cognitive decline. However, its approval has been contentious, and its clinical benefits in improving cognitive function are still being debated.
• Lecanemab: Lecanemab, a promising amyloid-targeted therapy, is currently in clinical trials. Lecanemab, like aducanumab, is intended to clear amyloid-beta plaques from the brain, slowing cognitive decline in patients with early-stage Alzheimer’s disease. Preliminary data indicate that lecanemab may be more effective than previous amyloid-targeting drugs, providing hope for better outcomes.

2. Tau-Targeted Therapies

Tau tangles, in addition to amyloid plaques, accumulate in the brain and are associated with Alzheimer’s disease and other neurodegenerative conditions. Emerging therapies are aimed at reducing tau pathology in order to slow or prevent cognitive decline.

• Anti-Tau Vaccines: Scientists are creating vaccines that target abnormal tau proteins, preventing them from forming tangles and spreading throughout the brain. Early-stage clinical trials have yielded promising results, with some vaccines able to reduce tau buildup while preserving cognitive function in animal models.
• Tau Inhibitors: Small molecules that prevent tau aggregation are being studied as a treatment for Alzheimer’s disease and other types of dementia. These medications are designed to prevent the formation of tau tangles and stabilize the brain’s microtubule structures, which are critical for neuronal function and communication.

3. Gene Therapy & Neurogenetics

Gene therapy shows great promise for treating neurodegenerative diseases by targeting the genetic mutations that cause cognitive decline. Advances in CRISPR and other gene-editing technologies are paving the way for treatments that may correct or mitigate the genetic causes of Major Neurocognitive Disorder (NCD). These advancements seek to either alter the genes responsible for the production of harmful proteins or strengthen the brain’s natural protective mechanisms.

• CRISPR-Cas9 Gene Editing: CRISPR is a revolutionary gene-editing tool that enables scientists to precisely target and modify specific genes. In the context of Major NCD, CRISPR could potentially be used to edit genes that produce amyloid-beta plaques or tau tangles, two important factors in Alzheimer’s disease. Researchers hope that modifying these genes will reduce protein buildup and slow disease progression. Although this technology is still in its early stages of development, preliminary animal studies have shown promise, and human trials may begin soon.
• Gene Therapy for APOE ε4 Carriers: Individuals with the APOE ε4 allele have a significantly higher risk of developing Alzheimer’s disease. Gene therapy could reduce APOE ε4 expression or increase protective variants like APOE ε2, providing a potential solution. Researchers are currently looking into this approach as a way to reduce the genetic risk of neurodegeneration in high-risk populations.

4. stem cell therapy

Stem cell therapy is another promising treatment for Major Neurocognitive Disorder, with the potential to replace damaged or lost neurons and promote brain regeneration.

• Neural Stem Cells: Neural stem cells can differentiate into a variety of brain cells, such as neurons and glial cells. Scientists are looking into how stem cell transplantation can repair damaged brain tissue and restore cognitive function in people with dementia. In animal models, stem cell therapies have shown promise for improving memory and learning abilities. Human clinical trials are currently underway to assess the safety and efficacy of these treatments for Alzheimer’s disease and other neurodegenerative conditions.
• Induced Pluripotent Stem Cells (iPSCs): iPSCs are adult cells that have been genetically reprogrammed to function as embryonic stem cells. They can develop into any cell type, including neurons. Researchers are looking into how iPSCs can be used to generate new neurons in the brain, potentially replacing those lost due to neurodegenerative diseases. While this approach is still in its early stages, it holds great promise for future treatments of Major NCD.

5. Neurostimulation techniques

Non-invasive brain stimulation techniques, such as Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have gained popularity as potential treatments for slowing cognitive decline in patients with Major NCD.

• Transcranial Magnetic Stimulation (TMS): Magnetic fields stimulate specific areas of the brain. Recent research suggests that TMS may improve cognitive function in people with early-stage Alzheimer’s disease by increasing neural activity in regions involved in memory and executive function. TMS is a noninvasive, low-risk treatment that has already been approved for depression. Its potential use in dementia treatment is now being actively investigated, with preliminary results showing promise.
• Transcranial Direct Current Stimulation (tDCS): A low electrical current is applied to the scalp to modulate brain activity. According to research, tDCS can improve cognitive performance in tasks such as memory, attention, and problem solving, making it a potential therapeutic option for people with mild cognitive impairment (MCI) and early-stage dementia. The treatment is non-invasive and can be easily integrated into standard therapeutic regimens, making it a safe and accessible option for patients.

6. Digital therapeutics and Artificial Intelligence (AI)

Digital therapeutics and AI-based tools are transforming how cognitive decline is monitored and managed in people with Major NCD. These innovations use technology to provide personalized treatment plans, improve patient outcomes, and provide new insights into disease progression.

• Cognitive Training Platforms: Several digital platforms offer targeted cognitive training exercises to improve memory, attention, and executive function. These platforms employ adaptive algorithms to tailor exercises to the individual’s cognitive abilities and monitor progress over time. Some examples are BrainHQ and Lumosity, which have been shown to improve cognitive function in older adults and people with mild cognitive impairment. As digital therapeutics advance, they may become a valuable tool in delaying the progression of Major NCD.
• Wearable Devices for Monitoring: Wearable devices powered by artificial intelligence, such as smartwatches and fitness trackers, are increasingly being used to track cognitive health and detect early signs of cognitive decline. These devices can monitor a variety of metrics, including sleep patterns, physical activity, and heart rate variability, which have been linked to brain health. AI algorithms can detect subtle changes that may indicate deterioration in cognitive function, allowing for early intervention and more personalized care.
• AI in Diagnostic Imaging: Artificial intelligence is being used to improve diagnostic imaging accuracy in neurodegenerative diseases. Artificial intelligence algorithms can analyze brain scans (such as MRIs or PET scans) to detect patterns of atrophy or abnormal protein accumulation that may indicate Alzheimer’s disease or other forms of dementia. AI has the potential to improve patient outcomes by guiding treatment decisions with earlier and more accurate diagnoses.

7. Targeting inflammation and the gut-brain axis

New research suggests that inflammation and gut health play important roles in the onset and progression of neurodegenerative diseases. Innovative treatments targeting these pathways are gaining traction as potential treatments for Major NCDs.

• Anti-Inflammatory Therapies: Chronic inflammation is thought to accelerate the progression of Alzheimer’s disease and other dementias. Researchers are looking into how anti-inflammatory drugs, such as NSAIDs and specific immune-modulating therapies, can reduce brain inflammation and slow cognitive decline. While clinical trial results have been mixed, ongoing research aims to identify specific inflammatory pathways that can be targeted more effectively.
• The Gut-Brain Axis: The gut-brain axis is the complex communication between the gastrointestinal and central nervous systems. Recent research has shown that the gut microbiome’s health can have an impact on cognitive function, mood, and neuroinflammatory responses. Probiotics and prebiotics, which promote a healthy gut microbiome, are being investigated as potential treatments for cognitive health. Early research suggests that modifying the gut microbiome may reduce inflammation and improve brain health in dementia patients.

Holistic and Alternative Therapies for Major Neurocognitive Disorder

While traditional and innovative medical treatments are critical for managing Major NCD, holistic and alternative approaches can supplement these treatments by addressing the physical, emotional, and social aspects of the disorder. These approaches emphasize overall well-being and can improve the efficacy of traditional therapies.

1. Mindfulness & Meditation

Mindfulness-based interventions, such as meditation and mindfulness-based stress reduction (MBSR), can assist people with Major NCD in managing symptoms of anxiety, depression, and agitation. These practices are aimed at increasing present-moment awareness and reducing emotional reactivity, which is frequently associated with cognitive decline.

• Cognitive Benefits: Some research suggests that mindfulness meditation can improve attention, working memory, and emotional regulation in people with mild cognitive impairment and early-stage dementia. Mindfulness practices, which promote relaxation and reduce stress, can help improve overall cognitive function and quality of life.

2. Acupuncture

Acupuncture is a traditional Chinese medicine practice in which fine needles are inserted into specific points on the body to promote healing and balance the body’s energy (Qi). Acupuncture has been investigated for its potential to alleviate agitation, anxiety, and sleep disturbances in dementia patients.

• Symptom Management: Research indicates that acupuncture may help improve cognitive function and reduce behavioral symptoms in Alzheimer’s patients. It may also improve sleep and reduce anxiety, allowing patients to manage their symptoms more effectively.

3. Herbal Remedy and Supplements

Herbal supplements have been used for centuries to promote cognitive health, and some are being investigated as potential treatments for Major NCD. However, before taking any supplements, consult a healthcare provider because they can interact with prescribed medications.

• Ginkgo Biloba: Ginkgo biloba is one of the most extensively researched herbal supplements for dementia. It is thought to improve blood flow to the brain and has been shown to have mild effects on cognitive function in people with Alzheimer’s disease.
• Curcumin: Curcumin, the active ingredient in turmeric, has powerful anti-inflammatory and antioxidant properties. Some studies indicate that curcumin may help reduce amyloid plaque buildup and improve cognitive function in Alzheimer’s patients.

4. Musical and Art Therapy

Music and art therapy are non-pharmacological interventions that can provide significant emotional and cognitive benefits to individuals with Major NCD. These therapies engage various areas of the brain, promoting emotional expression, reducing anxiety, and improving cognitive function.

• Music Therapy: Listening to music or participating in music-making activities can improve mood, reduce agitation, and improve memory in dementia patients. Music therapy has been shown to improve communication and emotional well-being, even in the later stages of the disease.
• Art Therapy: Art therapy fosters creativity and self-expression, allowing people with cognitive impairments to communicate and process their emotions. It can also improve hand-eye coordination and social interaction, which is especially beneficial for patients who are experiencing social withdrawal.