What is Atrophic Alzheimer's Disease?

As we age, many of our hormones begin to decline. While this is the natural course of aging, these are the same molecules that feed and nourish our brains when we are young and healthy. When certain hormones and other trophic factors slip out of range, this can lead to atrophic Alzheimer’s.

So, what is atrophic Alzheimer’s? Atrophic Alzheimer’s is the second subtype of Alzheimer’s disease wherein the brain begins to downsize in response to a lack of hormonal and trophic support. Atrophic Alzheimer’s is correlated with a positive ApoE4 status and often presents with low levels of inflammation.

Atrophic Alzheimer’s can be a complex and very unique presentation of Alzheimer’s disease. For this reason, this post will cover the causes, signs, symptoms, and treatment of atrophic Alzheimer’s in detail. 

What Causes Atrophic Alzheimer’s?

Unlike some other subtypes of Alzheimer’s disease, there is no clear answer as to what causes atrophic Alzheimer’s. As it stands, we know that there are certain trophic factors (a combination of hormones and other molecules) that are important for the health and maintenance of a healthy brain. These are sometimes referred to as fertilizer for the brain. This fertilizer tells our neurons to build new connections, maintain old connections, and to create new memories. In individuals with atrophic Alzheimer’s, these trophic factors, or fertilizer, have become depleted and the brain cells begin to downsize as a response [1].

So, what are these trophic factors that are important to brain health?

Vitamin D

In the brain, vitamin D activates the DNA of neurons and stimulates the support of synapses (connection points between two neurons). We know that vitamin D levels tend to be lower in people with atrophic Alzheimer’s [1]. 

Adrenal Hormones

The adrenal glands are where we create hormones like DHEA, cortisol, and pregnenolone. Both cortisol and pregnenolone are made from DHEA. While pregnenolone goes on to become important hormones like testosterone and estrogen, cortisol sends the message to our body and brain that we are under some form of stress. When cortisol is chronically elevated, we can no longer create as many sex hormones and begin to lose another source of trophic support to the brain.  

Thyroid Hormones

The thyroid gland is what sets the metabolic rate for the rest of the body. When thyroid hormones dip low, the entire body slows down. This, of course, includes the brain. 

Sex Hormones

Sex hormones are often the first thing people think about when hearing the word “hormones”. Generally speaking, sex hormones refer to testosterone, estrogen, and progesterone. Though these sex hormones are most famous for their effects on the reproductive system, most are unaware of their roles in cognitive health. In fact, it is not uncommon for women to experience cognitive difficulties at the onset of menopause when sex hormones drop [2]. Similarly, it was found that men with low testosterone levels are more likely to experience cognitive decline as they age [3]. This is because sex hormones promote the growth of nerve cells and increase other trophic factors.

Brain Derived Neurotrophic Factor

BDNF is the molecule that the body uses to learn new things and create new memories. The idea of the brain being able to adapt to take new information, create new thought patterns, and create new memories is called plasticity. Healthy brains should be relatively plastic. BDNF is what allows our brains to do this [4]. It is common for individuals with atrophic Alzheimer’s disease to have lower levels of BDNF [5]. 

Nerve Growth Factor

NGF is one of the main chemicals that our brains use to promote the growth, development, and overall health of our neurons [6]. Unlike some of the other trophic factors listed above, NGF does not predictably go up or down during the progression of atrophic Alzheimer’s. Rather, we find that the system by which NGF usually keeps our brain cells healthy does not work as it is supposed to. This means that total NGF levels may go up, down, or not change at all [6]. 

Signs and Symptoms of Atrophic Alzheimer’s

• Like inflammatory Alzheimer’s, atrophic Alzheimer’s tends to be more common in those with one or two copies of the ApoE4 allele
• Symptoms tend to develop in the late sixties to seventies in those with an ApoE4 allele
• The most common type of memory loss is the difficulty to store new information
• Inflammation is typically not present or sometimes lower than normal
• Hormones tend to be out of the optimal range which are written below:
• • TSH: less than 2.0 mIU/L
  • Free T3: 3.2-4.2 pg/mL
  • Free T4: 1.3-1.8 ng/dL
  • Reverse T3: less than 20 ng/dL
  • AM Cortisol: 10-18 mcg/dL
  • Pregnenolone: 100-250 ng/dL
  • Estradiol: 50– 250 pg/ mL (women, age dependent)
  • Progesterone: 1-20 ng/mL (women, age dependent)
  • Testosterone: 500-1,000 ng/dL (men) 25-70 ng/dL (women)
  • Vitamin D: 50-80 ng/mL
  • Homocysteine: ≤7 μmol/ L

Treatment of Atrophic Alzheimer’s

In terms of treatment, there is no silver bullet solution that will work for everyone. As pointed out previously, there are many different trophic factors that are important to cognitive health. For each person, there will be a different emphasis on one factor versus another. This is why it is important to work with a functionally certified practitioner who can help to find the root cause of trophic dysfunction. Generally speaking, a thorough treatment will include finding the root cause, addressing dietary and lifestyle factors, and in some cases, supplementation.

Root Causes of Atrophic Alzheimer’s

Since we live distinctly different lives, our bodies all undergo different stresses and develop diseases differently. This means that low trophic support may be caused by adrenal fatigue in one person, and thyroid dysfunction in another. Identifying the root cause will allow for a successful intervention.

Diet and Lifestyle

As with everything else, this comes down to the individual. However, interventions will be aimed at improving the body’s innate capacity to produce trophic support for the brain. This typically requires a nutrient rich diet, moderate exercise, and stress reduction. Specific food plans and exercise recommendations should be tailored to the individual.

Supplementation

This is the largest gray area in the treatment of atrophic Alzheimer’s. As of right now, we know that simply replacing the trophic factors via supplementation does not solve the problem [7][8]. In some cases, blindly supplementing can cause harm [9]. The best supplements for atrophic Alzheimer’s as of right now are those that support the underlying mechanism of dysfunction (AKA the root cause). This must be determined by a professional.

Conclusion

Atrophic Alzheimer’s is a complicated disease and we still have a lot to learn in regards to its complexity. If you are worried that you may be at risk of atrophic Alzheimer’s, it is important to work with a doctor and dietitian who are trained in both the Bredesen protocol and functional medicine to find the root cause for a loss of trophic support. Contact the Amos Institute today to make an appointment with a dietitian trained in the Bredesen Protocol and functional medicine.

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References:

1. Bredesen, D. E. (2017). The end of Alzheimer's: The first program to prevent and reverse cognitive decline. Avery, an imprint of Penguin Random House.
2. Jaff & Maki, 2021, 10.1080/13697137.2021.1942700
3. Moffat et al., 2002, 10.1210/jc.2002-020419
4. Jiao et al., 2016, 10.1038/tp.2016.186
5. Spudic et al., 2022, 10.1016/j.psychres.2022.114772
6. Mufson et al., 2019, 10.1016/B978-0-08-021345-3.50024-1
7. Resnick et al., 2017, 10.1001/jama.2016.21044
8. Jett et al,, 2022, 10.3389/fnagi.2022.948219
9. Lai et al., 2022, 10.1111/acel.13670