Alzheimer’s Disease – Another Manifestation of Metabolic Disease

Alzheimer’s Disease – Another Manifestation of Metabolic Disease


Neurodegenerative disease (dementia, etc.) is arguably the area of greatest failure in medicine. There have been billions of dollars spent on over 400 failed clinical trials in Alzheimer’s Disease, and the best drugs that emerge from the rubble fail to show any improvement.  Alzheimer’s drug trials have a 99.6% failure rate.

Alzheimer’s Disease is not a normal part of aging.

Alzheimer’s Disease is increasingly common, estimated to impact at least 1/3 of Americans – whether affecting individuals

directly or friends/family as caregivers.  Traditionally thought of as a disease that affects the elderly, it is increasingly common in younger ages, such as in 50 year-olds.

The majority of dementia is due to poor metabolic health

There are many factors that may contribute to the development of dementia.  Alzheimer’s Disease is a specific type of dementia that accounts for 60-80% of dementia, whereas other major causes of dementia include cerebrovascular disease (aka vascular dementia), Lewy Body Disease, Parkinson’s Disease, etc.

In Alzheimer’s Disease, the links to poor metabolic health, via Insulin Resistance, are so well documented that it is often referred to as “Type 3 Diabetes”.   Also, note that vascular dementia – a consequence of strokes, usually a history of small (sometimes imperceptible) strokes over time that have a cumulative negative impact on global brain functioning – is usually a complication of metabolic disease.

What causes Alzheimer’s Disease?

Alzheimer’s Disease is a result of the body’s protective response to metabolic and toxic disturbances: inflammation, insulin resistance and glucose toxicity, nutrient withdrawal, and specific toxins.  There are dozens of things that contribute to this response.

In health care, we treat without knowing the cause of dementia.  There has been a search for “the cause” of Alzheimer’s, but it is becoming evident that there is actually a multitude of factors, as identified by Dale Bredesen, MD, a physician researcher focused on Alzheimer’s Disease.

His lab hasn’t seen a single patient without at least 10 factors known to contribute to Alzheimer’s.

ApoE4 is the most common genetic association with Alzheimer’s.  About 65% of Alzheimer’s patients are ApoE4-positive; only 25% in general population.  If you have the ApoE4 gene, it is not inherently bad; it’s just that your optimal diet and optimal lifestyle is different from someone with ApoE3 instead.  ApoE4 directs more resources into pro-inflammatory processes; it makes one very good at fighting off pathogens, whereas ApoE3 makes one good at recycling and longevity and not very good at fighting off pathogens.  However, the long-term inflammatory state of ApoE4 puts one at more risk for developing Alzheimer’s.

Amyloid appears to be a mediator of disease, not a causative agent.  Note: There was a recent reveal of fraudulent research from 2006 that had claimed amyloid to be causative of Alzheimer’s Disease.

Metabolic Health and Alzheimer’s Disease

Several metabolic factors are also implicated in Alzheimer’s Disease (note: there may not be an established cause-effect relationship):

Insulin resistance – A 2004 study of autopsy data revealed that 81% of patients with Alzheimer’s had either Type 2 Diabetes or pre-diabetes.  Note, however, that referring to Alzheimer’s as “type 3 diabetes” is an oversimplification. Insulin resistance and glucose toxicity contribute to the inflammatory type of Alzheimer’s, and alteration of insulin signaling contributes to the atrophic type of Alzheimer’s. Thus, it is more appropriate to say that a subset of Alzheimer’s could be thought of as “Type 3 Diabetes”.


Hemoglobin A1c

Carbohydrate intake


Visceral fat

Mitochondrial dysfunction

Circadian dysregulation

Vegetable oil

Sleep deprivation

How is Alzheimer’s Disease diagnosed?

The criteria used to establish a diagnosis of Alzheimer’s Disease are established by consensus opinion, i.e. a panel of physicians, and the criteria are subject to change over time.  The original criteria were established in 1984 defined Alzheimer’s as a single stage of disease – dementia.  Diagnosis could only be confirmed at autopsy by the presence of the typical findings of amyloid plaques and tau tangles in the brain.  Later research determined that symptoms of Alzheimer’s often appear many years before the symptom of dementia and that the brain changes do not necessarily correlate with the disease.

The criteria were modified in 2011 to reflect this new knowledge and now define 3 stages of Alzheimer’s Disease:

  • Pre-clinical: relevant to research settings only, where amyloid plaques and nerve cell changes are evident.
  • Mild Cognitive Impairment: memory problems, but not enough to compromise an individual’s function.
  • Alzheimer’s Dementia: the final stage of the disease, where one’s cognitive decline has negative impact on function. In addition to memory loss, may also be evident as word-finding difficulty, visual/spatial issues, impaired reasoning, or impaired judgment.


The spectrum of cognitive impairment

Just as most things in life exist on a continuum, so does cognitive impairment.  The brain changes that characterize Alzheimer’s Disease start long before one meets the formal criteria of dementia – decades before, even.

In one study of individuals genetically susceptible to Alzheimer’s Disease, levels of amyloid were significantly increased 22 years before symptom onset, glucose metabolism began to decrease 18 years before onset, and brain atrophy (shrinkage) began 13 years before onset.

spectrum of cognitive impairment

Furthermore, an individual’s baseline level of cognition may greatly impact the time of diagnosis.  For example, cognitive impairment in a high-functioning individual may not be evident until it has become quite severe, whereas a smaller degree of impairment may trigger alarm in someone on the other extreme.  This discrepancy has significant implications in terms of how soon the disease is recognized and interventions can be implemented.

Consistent with the ambiguous definitions of Alzheimer’s Disease, 90% of primary care physicians acknowledge that it is hard to know where Mild Cognitive Impairment ends and dementia begins.


Alzheimer’s Disease, the most common form of dementia, is not a normal part of the aging process.

The majority of Alzheimer’s Disease is a consequence of poor metabolic health.

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