Amy Savagian MD
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My hope with these posts is to empower others.  I  want to share my interests: those things that enthrall me and I think will interest you.  The posts are not meant to give medical advice, but is meant simply to share the information related to health, wellness and longevity that I find fascinating right now. The first four posts starting October 2019 are the foundation for my lifestyle medicine practice.

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Cognitive Health & Prevention of Dementia

2/4/2023

 
Cognitive health is one of our most valuable assets, and a large part of improving healthspan is staving off cognitive decline. The majority of my patients have normal cognitive function and would like to prevent cognitive decline.

Why is cognitive health an important focus? Approximately one-third of individuals 65 years and older had dementia or mild cognitive impairment (MCI) [Jama]. According to Alzu.org, a website put together by doctors at Weill-Cornell, up to 40% of MCI and dementia cases are preventable. Interestingly even in those whose dementia may not be entirely preventable, it may be possible to delay the onset symptoms. 

The area of risk reduction or preventing cognitive decline is very new and it is changing quickly.  At our practice we start by taking a good clinical history and looking at the ABC’s (Anthropometrics, blood biomarkers and cognitive functioning. This allows us to do a risk assessment and early intervention.  

Examples of anthropometrics include BMI, muscle and body fat evaluations. Blood biomarkers include markers of metabolism such as hemoglobin A1c and cholesterol, markers of inflammation such as hs-crp and genetics such as APOe4. The cognitive testing that we perform is using a platform called CNS Vital Signs. This tests areas of cognition such as processing speed, motor speed, memory and executive function. Below is a sample report of this testing.

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What can we do to optimize cognitive health? We first need to generally understand the mechanisms that are believed to contribute to cognitive decline.  These include: abnormal glucose metabolism, inflammation, oxidative stress, poor trophic factor signaling, and dysfunctional calcium flux (Isaacson et al 2018). In the section below I will discuss each of these and then lifestyle factors that may modulate the mechanisms contributing to cognitive decline.

Abnormal glucose metabolism:
Poor glucose metabolism, as seen in diabetes and overfed states such as obesity are known to contribute to insulin resistance at the level of the neuron. Type 2 diabetes is generally a state of hyperinsulinemia (high insulin). This state promotes neuronal inflammation and amyloid deposition. Interestingly, a high-fat, low-carbohydrate ketogenic diet, which is known to limit insulin production, in mice that genetically over-express amyloid beta resulted in a 25% reduction of amyloid burden compared to mice on a standard diet (Van der Auwera et al., 2005).

Inflammation:
Inflammation is also thought to worsen cognitive function. Studies have shown elevated inflammatory markers in patients with Alzheimer's Disease (AD). To modulate this inflammation, we can consider decreasing dietary sugars, adding in medications or supplements to decrease inflammation and assuring adequate sleep (as sleep deprivation increases biomarkers of inflammation) (Irwin et al., 2006). Social engagement may also play a role in decreasing the risk of AD by improving immune function (Bower et al., 2003, Friedman et al., 2007).

Oxidative stress: 
Patients with AD show many signs of oxidative stress including protein and DNA oxidation as well as lipid peroxidation. The increased oxidation comes from reactive oxygen species (ROS). ROS is important for normal cellular activity, but when there is an imbalance between the production and clearance of ROS the cell undergoes oxidative stress. People with APOe4 have increased markers of oxidative stress (Jofre-Monseny et al., 2008). To decrease oxidative stress, we need to increase the clearance of ROS or decrease the production.  

Trophic Factors: 
Trophic factors are basically growth factors. They include molecules such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) that are responsible for brain plasticity and improving cellular survival by preventing activation of the caspase system. BDNF is particularly important in the hippocampus (where  memory consolidation occurs). In AD, people have less trophic factors, which in the presence of increased amyloid can lead to neuronal death. (Guo et al., 1997)

Amyloid burden:
In AD, patients are known to have increased extracellular amyloid.  The role of amyloid is not fully understood–some people liken it to scar tissue, but as it accumulates, it causes more inflammation and increases oxidative stress. Interestingly, the oxidative stress, impaired glucose metabolism and inflammation can also lead to more amyloid deposition.

Dysfunctional calcium signaling:
In AD we see increased intracellular and mitochondrial calcium. These elevated levels can increase ROS, leading to increased oxidative stress, inflammation and amyloid production. Together this leads to increased rates of cell (neuronal) death. 

Reducing risk should have a multi-factorial approach.  Each approach may reduce risk across several domains. For example treating insulin resistance may help with glucose metabolism and downstream effects of inflammation and oxidative stress. Watson and Craft (2003) demonstrated that treating insulin resistance may reduce the risk of AD.

Targeted nutrition can reduce the risk of AD through mechanisms of insulin resistance, inflammation and oxidative stress. We can improve insulin resistance by reducing processed sugars and the overfed state. Diets such as a mediterranean or low carb diet have been shown to be helpful.  (Scarmeas et al., 2009, Volek et al., 2004).

Sleep deprivation has been shown to increase inflammatory cytokines. Assuring adequate sleep will decrease inflammation, improve insulin resistance and help with calcium toxicity. 

Stress management can help reduce cortisol levels that impact insulin resistance, oxidative stress, trophic factors, calcium toxicity and amyloid burden.

Exercise both resistance and aerobic helps with glucose metabolism, insulin resistance, oxidative stress and trophic factors.

Hormone replacement may lower amyloid burden and improve trophic factors. 

Drugs can target inflammation, oxidative stress and amyloid.  

Supplements may also play a role as it relates to insulin resistance, inflammation, oxidative stress and calcium toxicity.

Based on cognitive testing results we may also consider specific interventions that engage executive planning, motor speed, processing speed and more.

Alzheimer’s and mild cognitive impairment has a long window of brain changes before any symptoms arise. With monitoring and a targeted lifestyle plan, we can significantly reduce the risk of dementia.

References:
Alzheimer's Universe. Weill Cornell Medicine. Retrieved November 30, 2022, from https://www.alzu.org/.
 
Bower, J. E., Kemeny, M. E., Taylor, S. E., and Fahey, J. L. (2003). Finding positive meaning and its association with natural killer cell cytotoxicity among participants in a bereavement-related disclosure intervention. Ann. Behav. Med. 25, 146–155. doi: 10.1207/S15324796ABM2502_11
Google Scholar

Friedman, E. M., Hayney, M., Love, G. D., Singer, B. H., and Ryff, C. D. (2007). Plasma interleukin-6 and soluble IL-6 receptors are associated with psychological well-being in aging women. Health Psychol. 26, 305–313. doi: 10.1037/0278-6133.26.3.305
Google Scholar

Guo, Q., Sopher, B. L., Furukawa, K., Pham, D. G., Robinson, N., Martin, G. M., et al. (1997). Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid β-peptide: involvement of calcium and oxyradicals. J. Neurosci. 17, 4212–4222.
Google Scholar

Isaacson et al. Mechanisms of Risk Reduction in the CLinical PRactice of Alzheimer’s Disease Prevention. Front. Aging Neurosci., 10 April 2018.doi: 10.3389/fnagi.2018.00096
Google Scholar

Irwin, M. R., Wang, M., Campomayor, C. O., Collado-Hidalgo, A., and Cole, S. (2006). Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch. Intern. Med. 166, 1756–1762. doi: 10.1001/archinte.166.16.1756
Google Scholar

Jofre-Monseny, L., Minihane, A. M., and Rimbach, G. (2008). Impact of apoE genotype on oxidative stress, inflammation and disease risk. Mol. Nutr. Food Res. 52, 131–145. doi: 10.1002/mnfr.200700322
Google Scholar

Manly JJ, Jones RN, Langa KM, et al. Estimating the Prevalence of Dementia and Mild Cognitive Impairment in the US: The 2016 Health and Retirement Study Harmonized Cognitive Assessment Protocol Project. JAMA Neurol. 2022;79(12):1242–1249. doi:10.1001/jamaneurol.2022.3543
Google Scholar

Van der Auwera, I., Wera, S., Van Leuven, F., and Henderson, S. T. (2005). A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr. Metab. 2:28.
Google Scholar

Volek, J. S., Sharman, M. J., Gómez, A. L., DiPasquale, C., Roti, M., Pumerantz, A., et al. (2004). Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women. J. Am. Coll. Nutr. 23, 177–184. doi: 10.1080/07315724.2004.10719359
Google Scholar
​

Watson, G. S., and Craft, S. (2003). The role of insulin resistance in the pathogenesis of Alzheimer’s disease. CNS Drugs 17, 27–45. doi: 10.2165/00023210-200317010-00003
Google Scholar

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