Cognitive Decline: A Deeper Dive

A Wiser Mind utilizes a Lifestyle-Based, Functional Health Approach for the Restoration and Maintenance of Brain Health and Prevention of Cognitive Decline as part of our Functional Health program for Cognitive disorders.  Where appropriate we also use talk therapy modalities delivered by Licensed Psychologists and Licensed Clinical Social Workers.  During consultations our clinical staff will help determine the types of services delivered to each individual.

Cognitive Decline

The current medical paradigm is that there is no cure for Alzheimer’s disease, and current treatments cannot stop it from progressing. But exciting new research is showing that individualized, targeted lifestyle interventions may be able to reverse the loss of cognitive function associated with subjective and mild cognitive impairment and even prevent progression to Alzheimer’s disease.

More than 16 million people in the United States are living with cognitive impairment1. An estimated 6.2 million Americans currently have Alzheimer’s disease (AD), the most well-known form of dementia. By 2050, the number of people age 65 and older with Alzheimer’s dementia is projected to reach 12.7 million. The estimated lifetime risk for Alzheimer’s dementia at age 45 is approximately 19.5%  for women and 10.3%  for men; the risk increases to 21.1% for women and 11.6% for men at age 65.2 Prior to the COVID-19 pandemic,  AD was estimated to be the third leading cause of death after heart disease and cancer and is currently considered the 7th leading cause of death in the US.3-5

Subjective Cognitive Decline (SCD)

Subjective cognitive decline (SCD), also known as subjective cognitive impairment (SCI), in older adults is increasingly recognized as a potential indicator of cognitive decline that is not associated with normal aging. There is emerging evidence of associations of SCD with brain changes characteristic of AD in the absence of measurable cognitive dysfunction. Subjective cognitive decline refers to self-perceived  worsening of memory and other thinking abilities by an individual, separate from cognitive testing, clinical diagnosis or anyone else noticing. Not all those who experience subjective cognitive decline go on to develop MCI or dementia but many do, and research suggests that SCD may be a forerunner of  eventual progression to dementia2,6,7. The conversion rate of SCD to MCI and AD in diagnosed SCD was reported to be 54.2%, of which 78.9% progressed to MCI in a 7-year follow up study8. In comparison, the risk of developing MCI or AD in the normal group was 14.9%, of which 71.4% developed to MCI. The risk for SCD group to develop to MCI or AD within 7 years was 4.5 times greater than that of no-SCD group.9

Mild Cognitive Impairment (MCI)

MCI follows SCD where testing shows deficits in

  • Memory
  • Organizing
  • Speaking
  • Calculating.

Persons with MCI are still able to perform activities of daily living (ADLs). MCI has an estimated annual conversion rate of 5%–17% to AD.10 Among those with MCI, about 15% develop dementia after two years.11 About one-third (32%) of individuals with MCI develop Alzheimer’s dementia within five years’ follow-up.12


Dementia is defined as a global cognitive decline in which many mental abilities are lost. Memory loss is one of the earliest symptoms, and difficulty with reading, writing, speaking, following a conversation, reasoning, calculating, organizing and planning and changes in personality are some of the characteristic aspects. The crucial difference between MCI and dementia consists of the presence of a significant impairment of ADLs.

There are many causes of dementia, including2:

  • Alzheimer’s disease
  • Cerebrovascular disease
  • Lewy body disease
  • Frontotemporal lobar degeneration (FTLD)
  • Parkinson’s disease (PD)
  • Hippocampal sclerosis (HS)
  • Mixed pathologies.

 Alzheimer’s disease (AD)

Alzheimer’s disease is characterized by progressive loss of memory and other cognitive functions. It is the most common form of dementia in the elderly which worsens over time and eventually leads to death. AD is characterized by two hallmark lesions: plaques which are mainly composed of amyloid beta peptides and tangles, which are composed of tau protein. The core hypothesis of the amyloid cascade model, which is critical to the current understanding of AD pathogenesis, is that accumulation of amyloid beta is an early event leading to neurodegeneration..

AD is caused when an intercellular protein named amyloid precursor protein is cut in such a way as to form amyloid beta, which is chemically sticky and eventually forms large plaques. The plaques in turn cause inflammation in the brain leading to neuron (nerve cell) degeneration. The protein tangles that are also a hallmark of AD are present inside the neurons themselves. The tangles interrupt nutrient transport up and down the neuron. Tau becomes twisted and collapses into the tangles in this process and that is what actually causes the interruption of intracellular (within the nerve cell) communication and signaling. Synapses and nerve cells in the hippocampus (the region of the brain primarily associated with memory) are destroyed impairing short‐term memory. Although plaques and tangles are regarded as the main hallmarks of AD the disease may be primarily a disorder of synaptic failure13,14. The brain changes that characterize Alzheimer’s disease is thought to begin 20 years or more before symptoms arise.2

AD is usually diagnosed15 based on person’s symptoms including memory loss and cognitive deficits so severe that person loses their ability to perform ADLs. Characteristics of AD include:

  • Memory loss that disrupts daily life
  • Challenges in planning or problem solving
  • Difficulty in completing familiar tasks at work, leisure or home
  • Confusion with time or place
  • Trouble understanding visual images or spatial relationships
  • New problems with speaking or writing
  • Misplacing things or losing the ability to retrace steps
  • Decreased or poor judgment
  • Withdrawal from work or social activities
  • Changes in mood

AD Risk Factors

  • Age2,16
    • 10 percent of persons age 65 and older have AD
    • The percentage of people with Alzheimer’s dementia increases with age:
      • 3 percent of people age 65-74
      • 17 percent of people age 75-84
      • 32 percent of people age 85
  • Genetics17,18
    • Early onset AD = 1-5% of AD patients
      • presenilin 1, presenilin 2, APP
    • Apolipoprotein E4 (ApoE4)
      • Negative, approximately 9-20% risk of AD
      • 1 copy inherited (from one parent, +/-), approximately 30-45% risk of AD, symptoms in 60’s-70’s; 75 million Americans
      • 2 copies inherited (1 from each parent, +/+), approximately 50-90% risk of AD, symptoms in late 40’s-50’s; 7 million Americans
  • Gender2
    • Two-thirds of AD patients are female
  • Head Injury19
    • Studies have shown a 51% increase in AD, comparing individuals with head injury to those without head injury
  • Neurovascular Dysfunction20,21
    • Vascular conditions such as hypertension, atherosclerosis, and high homocysteine level can contribute to dementia and influence one’s risk for AD
  • Diabetes22
    • Newly diagnosed diabetes and diabetes duration are associated with increased risk of development of AD
  • Emotional trauma/stress23
    • Studies have shown that chronic stress leads to structural degeneration and impaired functioning of the hippocampus (a brain structure that has a major role in learning and memory) which may account for the increased risk of developing dementia

The original amyloid hypothesis was defined by George Glenner, MD in 198324-25. Glenner discovered that senile plaque amyloid is made of “amyloid ẞ‐protein” and first hypothesized that Alzheimer’s is an amyloidosis, in which beta‐amyloid accumulation leads to tangles and neuronal cell death.

Amyloid Cascade

The amyloid cascade hypothesis continues to be the most widely-accepted explanation for the disease and the prevailing view in the field is still that dealing with amyloid can treat the disease. Of the 2173 clinical trials conducted for Alzheimer’s treatment through 2019 22.3% were based on the Amyloid Hypothesis.26 However, the continual failure of drug trials has led some to question the model:

“According to the amyloid hypothesis, Alzheimer’s dementia begins in the brain with amyloid beta peptides accumulation and amyloid formation. The amyloid hypothesis has dominated Alzheimer research and clinical trials in the last 25 years. However, every trial, one by one and time after time, has failed to help anybody living with Alzheimer’s. Even worse, many trials even harmed the Alzheimer’s people…ongoing preventative trials on asymptomatic people at high risk, or genetically determined, for developing Alzheimer…are going to fail too because brain Aβ amyloid is not the cause of Alzheimer’s.”27

And, “to summarize this review of the history and progress of hypotheses and clinical trials for AD, the most perplexing question is in regards to amyloid hypothesis and its failed clinical trials, which account for 22.3% of all clinical trials. The failure of these trials strongly suggests that it is better to treat Aβ deposits as a pathological feature rather than as part of a major mechanistic hypothesis.”28

After two late-stage clinical trials of the drug Aducanumab were discontinued in 2019 an article in the journal Alzheimer’s & Dementia found that “Biomarker data were consistent with target engagement, but no evidence was presented to correlate biomarker changes to cognitive benefits…Aducanumab’s efficacy as a treatment for the cognitive dysfunction in Alzheimer’s disease cannot be proven by clinical trials.” As a result, Howard Fillit, MD, Chief Science Officer of the Alzheimer’s Drug Discovery Foundation stated “At this point, we’ve done the right experiment and the hypothesis didn’t hold true.“29

None of the pharmacologic treatments (drugs) available today for Alzheimer’s dementia slow or stop the damage and destruction of neurons that cause Alzheimer’s symptoms and make the disease fatal. The U.S. Food and Drug Administration (FDA) has approved five drugs for the treatment of Alzheimer’s through 2020— rivastigmine, galantamine, donepezil, memantine, and memantine combined with donepezil.2 A sixth drug, aducanumab, was approved by the FDA in 2021 despite many experts, including an independent panel of neurologists and biostatisticians, advising the FDA that clinical-trial data did not conclusively demonstrate that aducanumab could slow cognitive decline as noted above. 10 out of 11 panelists ultimately voted that the presented data could not be considered as evidence of aducanumab’s effectiveness; the remaining panelist was uncertain. Aducanumab clears out amyloid-β, and the FDA approved the drug on the basis of its ability to reduce the levels of these plaques in the brain. Data also showed that aducanumab has non-negligible side effects. Around 40% of treated participants in the two trials developed brain swelling. Patients taking the drug would need regular brain scans to avert dangerous complications — a burden for patients, neurologists and health-care systems. “This is going to set the research community back 10–20 years,” says George Perry, a neurobiologist at the University of Texas at San Antonio and a sceptic of the amyloid hypothesis.30

New Paradigm of Alzheimer’s disease

The work of Dale Bredesen, MD, a professor at the Easton Laboratories for Neurodegenerative Disease Research at UCLA has uncovered the biochemical mechanisms behind the erosion of memory associated with Alzheimer’s disease. In his over 30 years of study, Dr. Bredesen has found that Alzheimer’s results from an imbalance in the brain’s neuroplasticity signaling.  Dr. Bredesen’s laboratory discovered that  depending on how the amyloid precursor protein is cut, the resulting fragments will support the cellular processes associated with memory formation and maintenance, such as the maintenance of synapses (“non-Amyloidogenic”), or destroy them (“Amyloidogenic”). This research suggests that those with AD, as well as those at risk for the disease, are on the “wrong” side of this crucial balance. In addition, manipulation of the APP derivative peptide balance leads to predictable effects on learning and memory. In effect, APP signaling can be manipulated to inhibit AD pathophysiology. Dr. Bredesen discovered that there are at least 36 factors that affect whether the brain goes down a synapse-destroying pathway that ends in AD or a synapse-preserving pathway that reverses cognitive decline and maintains brain health31-33.

Dr. Bredesen developed the ReCODE (REversal of COgnitiveDEcline) program based on decades of research on the neurobiology of AD. Dr. David Ward, DC is a Certified ReCODE 2.0 practitioner of this comprehensive personalized program designed to improve cognition and support a healthy aging brain. This Functional Health approach is a targeted lifestyle modification plan designed to identify and address the underlying factors driving cognitive decline. In 2018 Dr. Bredesen published a paper in the Journal of Alzheimer’s Disease & Parkinsonism that described 100 patients with cognitive decline treated with this multi-component, precision healthcare approach, and showing documented improvement.

A recent publication provides further support for the effectiveness of this multifactorial, comprehensive and personalized therapeutic program approach for mitigating Alzheimer’s disease risk factors and restoring and maintaining cognitive function. As noted above this program for reversing symptoms of cognitive decline and optimizing brain health includes information on the metabolic factors that drive the symptoms of cognitive decline and provides detailed, personalized recommendations to address these factors, such as nutrition, exercise (physical and mental), sleep optimization, stress management, detoxification and dietary supplements. The results of an analysis of pre-and post-treatment cognitive scores of 255 individuals with cognitive impairment documented by a validated assessment tool showed that 74% of the participants’ cognition was stabilized and improved.

Where to Start the Lifestyle Intervention Process for Maintaining a Healthy Aging Brain

  • Identify Contributors – metabolic, immune, infectious, toxic, vascular, traumatic, genetic
  • Remove Contributors – insulin resistance, inflammation source(s), toxins, etc.
  • Create Resilience – optimize nutrients, hormones, trophic factors, neurotransmitters, etc.
  • Rebuild lost synapses and other structural and functional losses

Keys to Improving Cognition and Supporting a Health Aging Brain  with a Lifestyle-Based Functional Health Approach

The Functional Health approach involves developing a therapeutic partnership with your healthcare provider to develop lifestyle modifications to address identified physiological imbalances and create strategies for supporting brain health including:

  • Support balance between the parasympathetic (“rest-and-relax”) and sympathetic (“fight-or-flight”) nervous system
  • Enhance bioenergetics, including the brain’s ability to make and use energy to support synaptic growth and maintenance
  • Promote insulin sensitivity
  • Optimize trophic support, such as growth factors, hormones, nutrients
  • Optimize immune system function to promote resolution of Inflammation
  • Optimization microbiome function
  • Support synaptogenesis, neurogenesis and neuroplasticity
  • Reduce chronic toxic burden

References and Citations

At A Wiser Mind our focus is working with persons experiencing SCD and early MCI.  For more information about our program and to explore whether our lifestyle-based approach for supporting brain health is right for you, please click here, or use the scheduling widget to schedule a free discovery consultation with Dr. Ward.