• Dr. Rana Mafee

Conquering Cognitive Decline


Cognitive decline is a growing issue, but new therapies are promising to slow the trend.

Chronic illness is on the rise: diabetes, autoimmune diseases, allergies, autism and developmental disorders to name a few.  Arguably the most devastating and burdensome on patients and families are cognitive decline and dementia.  

Currently, Alzheimer’s Disease affects 33 million people worldwide. Some forecasts estimate 45 million Americans alive right now will develop Alzheimer’s Disease during their lifetime.

Disregarding the extreme emotional cost dementia extracts, this level of illness will wreak havoc on our health systems. The U.S. already spends $300 billion annually fighting Alzheimer’s, and the current growth rates of the disease and its costs would bankrupt Medicare in the 1-2 decades.

The good news is this doesn’t have to be our future.  

In just the last two decades, research has unlocked new insights to the various causes underpinning cognitive decline, as well as tools to offer patients.  Whether you or a loved one are suffering from mild or marked cognitive decline, we now have tremendous hope for not only a brighter future, but for frank reversal of cognitive decline.   

If you’ve been diagnosed with Alzheimer’s or some other form of dementia, read on and know that hope exists. If you are middle age and starting to notice brain fog, forgetfulness, or a lack of sharpness, read on and know that early intervention can help prevent cognitive decline and enhance your focus and mental capacity. If you have a strong family history of dementia and want to take every measure to protect yourself from this devastating fate, read on and be empowered that you can ensure decades of vitality and preservation of your cognitive faculties, despite your genetic footprint.   

Changing Views:

Our current challenges in reversing dementia aren’t for lack of trying.  

Miracle drug cures for dementia remain elusive.

Researchers have conducted over 400 clinical trials on therapies for dementia in the last several decades- all unsuccessful.  Pharma companies launched 244 trials in one decade alone.  243 of the trials failed (the one drug that passed – memantine – is now commercially available and indicated for Alzheimer’s dementia, but has very minimal clinical effects).   

The common methodology of all of these trials is a focus on monotherapy: one drug for one disease. 


What have we learned from our research, besides more proof to Einstein's quotation “the definition of insanity is doing the same thing over and over again and expecting a different result”?  We’ve learned that we need a paradigm shift.  Luckily, as research gets more sophisticated and nuanced, we are heading in that direction.   

The (short) Medical Stuff:

Amyloid beta (a protein) has been the focus of reaserch.

While the exact cause of dementia or Alzheimer’s Disease are not fully understood, the prevailing theory and focus of research has been on a key protein: amyloid beta. Excessive amyloid appears to be toxic to neurons. While researchers originally looked for ways to eliminate amyloid from brains, we now have a more nuanced view of their function. Amyloid, in particular, actually has a responsive and protective effect, acting as a potent anti-microbial agent while binding and removing toxic metals.  Amyloid is a potent pathogen fighter, but if things go haywire, the results can include destroying healthy synapses in addition to pathogens.  (This is part of the reason drug therapies have proven elusive – we're trying to balance amyloid beta correctly, not accelerate or eliminate them completely, This sweet spot is different in every individual).   

So, if it’s not amyloid beta, then what else could cause cognitive decline?  

The ReCode Approach 

As a pioneer in the research on the prevention and reversal of cognitive decline, we owe a debt of gratitude to Dr. Dale Bredesen and the ReCODE protocol he has developed.  Earning his medical degree from Duke University and training in neurology at the elite University of California San Francisco, Dr. Bredesen has dedicated his life to the study of aging and cognitive decline.  He is now an internationally recognized expert on neurodegenerative diseases and their mechanisms, and he has opened doors to new treatment approaches.   


There may be up to 36 factors that lead to dementia.

Dr. Bredesen’s decades of research have uncovered not one, but at least thirty six contributors to cognitive decline. Think of these like holes in the roof of your house.  For some, one big enough leak may be all it takes to notice changes.  For others, it is the combination of small leaks over time that accumulates into a large problem.  As with roof repair, the key is to identify ALL the leaks, patch each of them, then get to work on repairing other damage.   

Dr. Bredesen’s research focuses on finding interventions to trigger growth and preservation of the 500 trillion synapses between neurons – combatting the destructive forces of the different types of dementia.  The goal is to tip the balance in favor toward an environment in a patient’s brain that is synaptoblastic (productive) over synaptoclastic (or destructive).  AKA – repair the holes in the roof.


The cumulative impact of Dr. Bredesen’s work was published in the Journal of Alzeheimer’s Disease and Parkinsonism in 2014 where he discussed reversing cognitive decline across 100 patients.



Generally speaking, the 36 contributing factors group together into 6 sub-types of dementia, as defined and outlined by Dr. Bredesen. Most patients will experience a blend of these sub-types.

1) Inflammatory dementia:  Chronic inflammation is now widely understood as a root cause of most chronic illness. Those with cognitive decline commonly have some degree of chronic inflammation driving illness. Inflammatory foods, unwanted bacteria, yeast or other pathogens and toxins are drivers of inflammation, which slowly degrade your brain’s synapses.


2) Atrophic dementia stems from inadequate production of hormones and trophic factors. Deficiencies of thyroid hormone, estrogen, testosterone and several types of nerve growth trophic factors are linked with cognitive decline.

3) Glycotoxic dementia has origins in a diet of highly processed / high-sugar foods as well as resistance to insulin. There is a strong link between insulin-resistance (a cause of diabetes and pre-diabetes) and dementia.

4) Toxic dementia comes pathogens and toxins that have nestled into a patient’s brain. In fact, autopsy studies on the brains of patients with Alzheimer’s disease have shown presence of pathogens such as certain oral bacteria, Herpes Simplex type 1, Borrelia (the bacterial cause of Lyme Disease) and Candida (an immunotoxic yeast). And after 2020, we are now in uncharted territory with the emergence of COVID-19, with the noted long-term effects on cognition so far.

5) Vascular dementia: Adequate blood supply, and integrity of cerebral blood vessels, are essential for cognitive function. For those with a history of or predisposition for vascular disease, vascular dementia can be a significant player.

6) Traumatic dementia: chronic repeated traumatic brain injury is a known risk factor for dementia. Deposits of a protein called "tau" are noted to be a core feature. Often times, these patients are also low in trophic factors and hormones.

Every patient suffering from cognitive decline will have a different combination of these factors at play, so every treatment needs to be tailored to the individual case. Unfortunately, traditional evaluations and treatment plans typically do not account for all of these noted factors like nutrient deficiencies, toxic exposures, chronic infections and the inflammation they leave in their wake.

Fixing the leaks:

With roots in individual evaluation and protocols and a focus on lifestyle solutions, Integrative and Functional Medicine is tailor made to treat dementia, leveraging the work of Dr. Bredesen and his ReCode protocol.

The ReCODE protocol is rooted in lifestyle choices, identical to the foundation of care at Case Integrative Health. The fundamentals of functional medicine, diet, sleep, exercise and stress, are all key to reversing cognitive decline.

ReCode emphasizes:

A diet focused on driving ketosis (or a diet that is low-carb, high-healthy fat and protein consumption).

Ensuring adequate quantity and quality of sleep (I.e. addressing sleep apnea or other obstacles).

Exercising regularly, as this is one of the best ways to increase nerve growth factors in the brain (brain derived neurotrophic factor or BDNF). Think of BDNF like fertilizer for your brain.

And finally – try to forget stress (seriously!). Managing stress is one of the hardest lifestyle factors to address. Stress causes inflammation but also results in shrinking of brain tissues, especially in regions of the brain related to memory and cognition.

In Conclusion: We're only at the start!

Dementia is a complex illness, and hundreds of failed trials have confirmed that the one disease, one drug model is clearly insufficient to optimally prevent and reverse this condition. However, by working with a doctor trained in functional medicine, there is hope.

By building a foundation of optimal lifestyle choices, then identifying and addressing the “holes in your roof”, we can help prevent the dire outcome forecasted at the start of this blog.


As a neurologist trained in the age of little hope for dementia, I am now optimistic and thrilled to be able to offer an approach like the ReCODE program to my patients. From brain fog in your 40s, to frank dementia late in life, the ReCODE program offers extraordinary hope.








Dr. Rana Mafee

Director of Preventative Neurology

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