Alzheimer’s disease and other dementias are truly heartbreaking for patients and their families. Drug trials target amyloid-beta plaques in a bottom-level approach that has yet to be successful. In contrast, Functional Medicine offers a top-level approach that addresses the many underlying causes of dementia. Read on to learn about the lesser-known causes of Alzheimer’s disease, what nutrients support brain function, and what a Functional Medicine approach to dementia looks like.
More than 30 million Americans suffer from some type of dementia. Alzheimer’s disease (AD) in particular affects more than five million Americans, and its associated healthcare costs surpass $200 billion each year (1). Considering genetics and other risk factors, up to 45 million currently living Americans may develop AD within their lifetimes (2).
The hallmarks of AD are extracellular amyloid-beta plaques, intracellular neurofibrillary tangles, and activated glial cells in the brain. The conventional approach views amyloid-beta plaques as the enemy: the plaques build up, destroy synapses between nerve cells, and promote neuronal cell death, eventually leading to cognitive impairment. But conventional medicine fails to address what is causing and contributing to plaque build-up.
Nutritional deficiencies are associated with and sometimes can predict severity of Alzheimer’s disease and cognitive decline in the elderly. Learn which dietary patterns support dementia and brain health.
Alzheimer’s Is a Multifactor Pathological Condition
Dr. Dale Bredesen, a renowned AD researcher, challenges the mainstream view. I have interviewed him on my podcast and written about his work in this article. He argues that AD is a multifactor pathological condition. Amyloid-beta is not the main problem, but rather the brain’s response to one (or more than one) insult (3). By removing the insults and optimizing health, he has reversed AD in many cases. Through years of work, he has identified several types of AD, each with unique causes (4, 5):
- Type 1 (“inflammatory”) is due to an antimicrobial response to pathogens or other inflammatory causes.
- Type 2 (“atrophic”) is associated with reductions in factors that support brain health, like estradiol, progesterone, testosterone, insulin, and vitamin D.
- Type 1.5 (“glycotoxic”) is a composite of types 1 and 2. Inflammation from high blood glucose levels combines with a trophic loss of insulin sensitivity.
- Type 3 (“toxic” or “cortical”) is associated with exposure to toxins such as heavy metals, insecticides/pesticides, antimicrobials, and commercial/industrial toxins.
- Type 4 (“vascular”) is associated with reduced vascular support.
- Type 5 (“traumatic”) is associated with previous head trauma.
Monotherapy Isn’t the Answer
The quest for a miracle AD pharmaceutical has been expensive and fruitless. Most AD drug trials have targeted amyloid-beta itself or BACE1, the protease that catalyzes the rate-limited step in synthesizing amyloid-beta from amyloid precursor protein (APP). By treating a symptom and failing to address the underlying problem(s), more than 99 percent of monotherapy trials to halt or reverse AD have been unsuccessful (6).
In contrast, a Functional Medicine approach to AD identifies the underlying insults—inflammation, oxidative stress, nutrient deficiencies, atrophy, toxins, pathogens, or some combination—and treats them on an individualized basis. Using this method, Dr. Bredesen has seen dramatic improvements in AD. One patient’s hippocampal volume increased from the 17th percentile to the 75th percentile after 10 months of treatment (2). In several cases, his patients have been able to return to work following treatment (7). This article will focus on the nutritional strategies for managing cognitive decline, and in particular, AD.
Nutritional and Dietary Strategies for AD
Malnutrition affects the elderly disproportionately, varying from up to 10 percent for independently living people to up to 60 percent of institutionalized patients (8). Nutritional deficiencies are associated with and sometimes can predict severity of AD and cognitive decline in the elderly (9, 10, 11). Below I’ll explore dietary patterns that support dementia and brain health.
Nutrient-Dense, Paleo Diet
If patients are not already eating a Paleo diet, it is never too late to start. The Standard American Diet, full of processed grains, refined sugars, and industrial seed oils, doesn’t provide many nutrient-dense foods. A Paleo diet is rich in meats and organ meats, bone broth, fermented foods, vegetables, and other nutrient-dense foods. A Paleo diet also offers sufficient protein required for brain health. Amino acids, the building blocks of proteins, provide the precursors for neurotransmitters (norepinephrine, epinephrine, dopamine, serotonin, acetylcholine, etc.).
Because oxidative stress contributes to the pathogenesis of AD, diets rich in antioxidants like vitamin C, vitamin E, and beta-carotene are beneficial for preventing and supporting AD. A Paleo diet offers a large variety of fruits and vegetables replete with antioxidants. Whenever possible, obtain nutrients from whole foods, where synergistic cofactors and enzymes are also present.
Dietary antioxidants do not have the same effect as do supplementals, although a few studies have shown benefits. In the Rotterdam study, people with the highest intakes of vitamin C and vitamin E had lower risks of developing AD (12). In the Cache Country Study, which followed a population at risk for AD, supplementing with vitamins C and E in combination (but not each alone) correlated with reduced AD prevalence (13).
Folate and Other B Vitamins
Folate and other B vitamins regulate the level of homocysteine, which in excess has been associated with brain atrophy and higher risk of AD (14, 15). Likewise, lower levels of B vitamins are associated with cognitive impairment in old age and have been related to decreased brain volume (11, 16). In an elderly population followed for an average of six years, those with the highest total folate intake had a lower risk of developing AD compared to those with the lowest intake (17).
Compared to placebo, supplementing with folic acid, vitamin B6, and vitamin B12 in combination slowed the rate of brain atrophy in older patients with mild cognitive impairment (18). Overall, B vitamin supplementation trials have yielded mixed results, possibly because methylation support, often needed when patients are vitamin B-deficient, was not considered, or because the supplement formulations weren’t ideal. Additionally, it’s unlikely that B vitamin deficiency was the only contributing factor that needed to be addressed.
Ideal supplements for folate will contain a form of methylfolate and not synthetic folic acid. For vitamin B12, I prefer Trifolamin, which contains three bioavailable forms of B12 instead of the synthetic cyanocobalamin found in most supplements.
Omega-3 Fatty Acids
The human brain is 60 percent fat, and almost half of that fat is the omega-3 fatty acid DHA. A higher-fat diet in the NHANES population was associated with better processing speed, learning, and memory in healthy young and middle-aged adults (19). Higher intake of fish, of which certain varieties are rich in omega-3 fatty acids DHA and EPA, was negatively associated with dementia incidence in several studies (20, 21). One study showed decreased serum DHA levels in AD patients compared with healthy controls (22).
Clinical trials examining DHA/EPA supplementation in healthy and cognition-impaired older populations have shown mild cognitive benefits (9). A six-month clinical trial demonstrated improved cognitive performance in an elderly group following 2.2 grams per day of fish oil supplementation (23).
As always, I prefer patients to obtain nutrients from whole foods. A pound of cold-water fish per week should provide sufficient DHA and EPA. Extra virgin cod liver oil, also rich in vitamins A and D, is also an option, especially if patients aren’t getting enough sun exposure or eating vitamin A-rich liver.
Recently, I wrote an article on the undeniable link between diabetes and AD. In a study of more than 1,000 elderly men, diabetes increased the risk of any dementia by 65 percent over the 12-year average follow-up (24). Many other studies confirm this relationship (25).
Chronic hyperglycemia promotes amyloid-beta production and is associated with poorer cognitive performance (26, 27). High levels of insulin are also associated with poor cognition and increased risk of Alzheimer’s (28, 29, 30). The health benefits of optimizing insulin sensitivity and glucose levels are innumerable.
Other Supplements to Consider
The brain-boosting nutrients below are most effective as a synergistic blend. One option is Memory Pro by Pure Encapsulations.
- Curcumin: Pprotects brain cells from oxidative stress, improves memory, and decreases inflammation (31, 32)
- Phosphatidylserine: Can improve memory, learning, concentration, and coordination (33, 34)
- Acetyl-L-carnitine: Stimulates energy production in brain cells (35)
- Bacopa: Boosts memory and cognitive performance (36, 37)
A brain–gut axis has been identified in many neurological disorders, including ADHD, autism spectrum disorders, and AD (38). The central nervous system and GI tract communicate with each other and together can impact intestinal motility, the release of neurotransmitters, and the intestinal immune system (38).
Microbial complexity tends to decrease with age, and those with AD have altered microbiomes compared to healthy older adults (39, 40). Alarmingly, one study found associations between antibiotic use in infancy and neurocognitive outcomes later in life (41). This reiterates how vital it is to take steps to repopulate the gut with beneficial microbes after a course of antibiotics.
In rat and mouse models, probiotics decreased brain inflammatory markers and slowed amyloid-beta accumulation (42, 43, 44). In humans, one clinical trial demonstrated benefits of probiotic supplementation on serum hs-CRP, an inflammatory marker, and some measures of cognitive function (45). Refer to my previous article for other ways to heal the gut in addition to probiotic supplements for AD patients.
Non-Nutritional Support for AD and Dementia
- Reduce toxic exposure and burden: Toxic exposure is especially common in type 3 AD.
- Eliminate pathogens: Pathogens increase inflammation, one of the underlying triggers in AD development.
- Hormonal support: Hormonal imbalances often accompany type 2 AD.
- Exercise: Exercise stimulates brain-derived neurotrophic factor (BDNF), which plays a crucial role in learning, memory, and mood regulation.
- Optimize sleep: Sleep helps to clear amyloid-beta.
- Reduce stress: Stress is associated with poor memory and cognitive function and also increases inflammation.