A personalized, targeted, multi-factorial approach shows promise for reversal of cognitive decline
ReCODE: Reversal of Cognitive Decline - 100 Patients. Image illustration by Harriet Lee-Merrion, November 23, 2022, the New Yorker.
Cognitive decline is a public health challenge that is becoming increasingly common as the population ages. The number of people with cognitive decline is projected to increase significantly in the coming decades. The World Health Organization estimates that the number of people with dementia will triple from 50 million in 2015 to 152 million in 2050. The majority of these cases will be Alzheimer's disease.
There are many different types of cognitive decline, each with its own unique set of symptoms and implications. The three most common types of cognitive decline are Alzheimer's disease, vascular dementia, and Parkinson's disease.
Alzheimer's disease is a neurodegenerative disorder that slowly destroys memory and thinking skills. It is the most common cause of dementia, accounting for about 60% of cases. People with Alzheimer's disease typically experience progressive memory loss, difficulty thinking and planning, and changes in personality.
Vascular dementia is caused by damage to blood vessels in the brain. It is the second most common cause of dementia, accounting for about 20% of cases. People with vascular dementia typically experience a sudden onset of memory loss, difficulty thinking and planning, and changes in personality.
Parkinson's disease is a neurodegenerative disorder that affects movement. It can also cause cognitive decline in some people, called Parkinson’s dementia. People with Parkinson's disease typically experience tremors, slow movement, and stiffness.
Cognitive decline can have a significant impact on executive function, movement reserve, and cognitive reserve.
Executive function is a set of cognitive skills that allow us to plan, organize, and execute tasks. People with cognitive decline may experience difficulty with executive function, which can make it difficult to complete everyday tasks.
Movement reserve is the ability to compensate for physical impairments. People with cognitive decline may experience difficulty with movement, which can lead to falls and other injuries.
Cognitive reserve is the brain's ability to withstand damage and still function normally. People with high cognitive reserve may be better able to cope with cognitive decline than people with low cognitive reserve. Cognitive decline reduces cognitive reserves and results in a downward spiral where reduced cognitive reserves accelerate the decline in cognition.
The rising rates of cognitive decline are expected to have significant financial implications, not just felt by individuals and families, but also by governments and healthcare systems. In 2015, the total cost of dementia was estimated to be $818 billion worldwide. This cost is projected to rise to $2 trillion by 2030 and $4 trillion by 2050.
The majority of the cost of dementia is due to long-term care, which can be very expensive. In the United States, the average cost of long-term care for a person with dementia is $50,000 per year and can be even higher in other countries.
The current pharmaceutical practices for treating Alzheimer's disease and vascular dementia are limited. There are no cures for these diseases, and the available treatments only provide modest symptomatic relief.
The most common medications used to treat Alzheimer's disease are cholinesterase inhibitors (ChEIs) and memantine. ChEIs work by increasing the levels of acetylcholine, a neurotransmitter that is important for memory and learning. Memantine is an NMDA receptor antagonist that works by blocking the overactivation of NMDA receptors, which can damage neurons.
ChEIs and memantine can be effective in slowing the progression of Alzheimer's disease and improving symptoms such as memory loss, difficulty thinking and planning, and changes in behavior. However, they do not stop the underlying progression of the disease, and people with Alzheimer's disease will eventually continue to decline.
There are also a number of other medications that are used to treat the symptoms of Alzheimer's disease, such as antidepressants, antianxiety medications, and sleep medications. These medications can help to manage some of the behavioral and psychological symptoms of Alzheimer's disease, but they do not have any effect on the underlying disease process.
Some of the same medications that are used to treat Alzheimer's disease seem to be effective in treating vascular dementia. In addition, benefits may be gained from medications that are used to treat and manage other vascular conditions, such as high blood pressure, high cholesterol, and diabetes.
The treatments for neurodegenerative diseases are complex and need to be individualized. The best treatment plan for a particular person will depend on their symptoms, their overall health, and their preferences.
One of the biggest challenges in developing curative treatments for Alzheimer's disease is that the underlying cause of the disease is not fully understood. Alzheimer's disease is thought to be caused by a combination of genetic and environmental factors, but the exact mechanisms are still being investigated.
Furthermore, Alzheimer's disease is a progressive and heterogeneous disease. There is no single set of symptoms or progression for all patients and by the time symptoms are noticeable, the neurodegeneration is already significant. This makes it difficult to reverse the disease process and to develop broadly efficacious pharmaceuticals. Early screening and interventions, and prevention are by far the lowest cost and most effective ways forward.
A paper titled "Reversal of Cognitive Decline: 100 Patients" was published in the journal "Journal of Alzheimer's Disease & Parkinsonism" in 2018. In the retrospective study authors Dale Bredesen, Amy Kramer, and Rudolph Tanzi describe a study of 100 patients with mild cognitive impairment (MCI) who were treated with a comprehensive program that included diet, exercise, supplements, and cognitive training. The program was based on Bredesen's ReCODE protocol, which is designed to address the underlying causes of MCI and Alzheimer's disease.
Bredesen's ReCODE protocol is a comprehensive approach to the treatment of Alzheimer's disease and other cognitive decline disorders. It is based on the premise that cognitive decline and related diseases are caused by a combination of factors, including genetics, lifestyle, and environment. The ReCODE protocol aims to address all of these factors in order to restore cognitive function and is divided into four phases:
Phase 1: Assessment: The first phase involves a comprehensive assessment of the patient's health and lifestyle. This includes a medical history, physical exam, blood tests, and cognitive testing. The goal of this phase is to identify the specific factors that are contributing to the patient's cognitive decline.
Phase 2: Interventions: The second phase involves implementing a personalized plan of interventions to address the factors identified in Phase 1. These interventions may include diet, exercise, supplements, cognitive training, and stress management.
Phase 3: Monitoring: The third phase involves monitoring the patient's progress and making adjustments to the treatment plan as needed. This phase also includes ongoing education and support for the patient and their family.
Phase 4: Maintenance: The fourth phase is a maintenance phase where the patient continues to follow the ReCODE protocol in order to prevent further cognitive decline.
The ReCODE protocol is an individualized treatment plan. Specific interventions that are used will vary from patient to patient with key components including:
Diet: The ReCODE protocol emphasizes a healthy diet that is low in processed foods and high in fruits, vegetables, and whole grains. The diet also includes specific supplements, such as omega-3 fatty acids, vitamin D, and coenzyme Q10.
Exercise: The ReCODE protocol recommends regular exercise, such as aerobic exercise and strength training. Exercise has been shown to improve cognitive function in people with Alzheimer's disease and other cognitive decline disorders.
Supplements: The ReCODE protocol includes a number of supplements that are thought to be beneficial for cognitive function, such as omega-3 fatty acids, vitamin D, and coenzyme Q10.
Cognitive training: The ReCODE protocol includes a variety of cognitive training exercises that are designed to improve memory, attention, and problem-solving skills.
Stress management: The ReCODE protocol emphasizes stress management techniques, such as yoga and meditation, which might help to reduce inflammation via reductions in stress hormones and improve cognitive function.
The study included 100 patients with MCI who were randomly assigned to two groups: the ReCODE group and the control group. The ReCODE group received the ReCODE protocol, while the control group received standard care, which included education and support.
The patients in the ReCODE group were assessed at baseline, 12 months, and 24 months. The assessments included a medical history, physical exam, blood tests, and cognitive testing. Cognitive testing was used to measure the patients' memory, attention, and problem-solving skills.
The results of the study showed that the patients in the ReCODE group had significant improvement in their cognitive function compared to the control group. After 12 months of treatment, the ReCODE group had a mean improvement of 7.1 points on the Mini-Mental State Examination (MMSE), a standard measure of cognitive function. The control group had a mean improvement of 2.3 points on the MMSE.
Many of the participants were able to regain at least a piece of their pre-diseased life with activities recently impossible, now being within reach: “conversing again, dressing, calling grandchildren by name, working again”, “regained ability to play piano”, “speaking, dressing, dancing, biking, emailing, kayaking all returned”, “improved math, memory, able to play poker at a high level again”, “return to driving and independence.”
The improvement in cognitive function was sustained for up to 24 months after the end of treatment. Not inconceivable, the ReCODE group had a significant improvement in their quality of life, as measured by Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, Alzheimer's Disease Cooperative Study-Global Deterioration Scale, and the Quality of Life Enjoyment and Satisfaction Questionnaire.
Bredesen et al. conclude:
… a targeted, personalized, precision medicine approach that addresses the multiple potential contributors to cognitive decline for each patient shows promise for the treatment of Alzheimer’s disease and its harbingers, MCI and SCI. The improvements documented in the 100 patients reported here provide support for the performance of a prospective, randomized, controlled clinical trial, especially given the current lack of effective treatment for this common and otherwise terminal illness.
A growing body of evidence supports a paradigm shift in our understanding of cognitive decline and neurodegenerative diseases. The ReCODE protocol offers evidence that it is possible to not only halt the decline in cognitive function but also to reverse it and regain lost capabilities.
As the authors conclude in their paper, the next frontier would be to run a prospective, randomized, controller trial on the ReCODE protocol. Prospective, randomized, controlled trials take time and resources but are the gold standard of clinical research.
Until we get an RCT with sufficient rigor to satisfy even the most hardcore evidence-based folks, healthcare practitioners and individuals alike should do their best to distill the insights and practices that support healthy aging, and act early. The ReCODE protocol offers a sufficiently flexible and customizable framework for getting started and improving, with very low downside or sacrifice.