Alzheimer’s Disease: The Great Morbidity of the 21st Century
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The role of diet, B vitamins, and omega-3 fatty acids in cognitive health
Alzheimer’s disease is one of the illnesses Americans fear most, affecting one in nine people over the age of 65.[1],[2],[3] The disease causes a gradual loss of memory, orientation, and reasoning, creating great difficulties for both the affected individual and for their family members.
American Scientist magazine calls Alzheimer’s “The Great Morbidity of the 21st Century,” noting that “Alzheimer’s disease bids to become in its own way as devastating in the foreseeable future as any of the great plagues of the past.”[4]
The brain damage associated with Alzheimer’s may begin a decade or more before memory problems appear.
The brain damage associated with Alzheimer’s may begin a decade or more before memory problems appear.[5] These changes include the accumulation of toxic beta-amyloid proteins, which form plaques that disrupt neural communication.[6],[7]
Researchers are beginning to unravel the steps involved in the onset and progression of Alzheimer’s disease. Although genetics plays a role, studies also suggest that one’s diet and lifestyle influence the risk of cognitive decline.[8] Today we’ll focus on the importance of omega-3 fatty acids and B vitamins in the maintenance of cognitive health.
The importance of omega-3 fatty acids
Omega-3 polyunsaturated fatty acids, which are associated with heart health,[9] also support brain health during aging.[10] People who consume diets enriched with omega-3 fatty acids have been shown to have a reduced risk of Alzheimer’s disease.[11]
Scientists at the National Institutes of Health recently evaluated the lifestyles and cognitive performance of more than 7,750 adults who were followed for five to 10 years.[12] The consumption of fish, the main dietary source of omega-3 fatty acids, was the most important dietary factor in lowering the risk of cognitive impairment.[13]
In another study, healthy postmenopausal women were first evaluated for omega-3 levels in the blood, and then they were followed up with a brain MRI scan eight years later.[14] Higher initial blood levels of omega-3s were associated with larger brain volumes after eight years, suggesting that omega-3s may protect against brain atrophy. The changes were especially pronounced in the hippocampus, a region associated with long-term memory.
Even in healthy young women aged 18 to 35, low DHA levels were associated with lower cognitive scores in the attention domain.
Docosahexaenoic acid (DHA) is the longest-chain omega-3 fatty acid in human diets.[11],[15] Individuals with Alzheimer’s disease have significantly less DHA in their blood and brain than those without the disease.[16],[17] Even in healthy young women, aged 18 to 35, low DHA levels were associated with lower cognitive scores in the attention domain.[18] Attention is the ability to actively process specific information in the environment while tuning out other details.
DHA has a direct effect on the preservation of brain neurons, since it serves as a precursor to neuroprotectin D1, a bioactive molecule that keeps brain cells healthy.[19],[20],[21],[22] Studies suggest that both DHA and neuroprotectin D1 inhibit beta-amyloid accumulation.[23],[24],[25]
A placebo-controlled clinical trial evaluated the effects of DHA supplementation in adults age 55 and older with age-related cognitive decline.[26] Supplementation with 900 mg of DHA per day for six months doubled plasma DHA levels and significantly improved memory and learning scores.[26]
The importance of B vitamins
Low levels of B vitamins (folate, vitamins B12, B6) also contribute to the risk of Alzheimer’s disease.[27],[28],[29]
B vitamin deficiencies cause an increase in blood homocysteine, an amino acid that becomes toxic at high levels.[28] When B vitamin levels are low, homocysteine cannot be properly metabolized and thus builds up in the blood and brain.[30]
Homocysteine harms the vascular and nervous systems, causing damage that is visible upon microscopic examination of the brain.[31],[32],[33] Even moderately raised homocysteine can double the risk of dementia.[28]
Green leafy vegetable consumption may actually help turn back the clock on aging.
Leafy greens are a good dietary source of folate, antioxidants, and other micronutrients. A prospective study of 960 adults, ages 58-99 years, showed that consumption of green leafy vegetables was associated with slower cognitive decline.[34] When comparing the highest daily consumption (median 1.3 servings a day) with the lowest (median 0.09 servings a day), the rate of cognitive decline among those who consumed the most vegetables was equivalent to being 11 years younger cognitively.[34] In short, green leafy vegetable consumption may help turn back the clock on aging.
In volunteers aged 70 and older with mild cognitive impairment, daily supplementation with B vitamins (folic acid, vitamin B12 and B6) reduced the rate of brain atrophy by 53% over a two-year period.[35] A 2018 report concludes: “Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline.”[28]
Clinical studies of folic acid and docosahexaenoic acid (DHA)
A series of eight randomized controlled clinical trials conducted by Tianjin Medical University (China) from 2016 to 2021, and published in peer-reviewed journals, evaluated the effects of supplemental folic acid and/or DHA in adults suffering from mild cognitive impairment.[36],[37],[38],[39],[40],[41],[42],[43]
Cognitive performance was assessed with the Full-Scale Intelligence Quotient (IQ), a summary score derived from an individual’s performance on a variety of tasks that measure acquired knowledge, verbal reasoning, attention to verbal materials, fluid reasoning, spatial processing, attentiveness to details, and visual-motor integration.
Six of the eight studies looked at the effects of supplemental folic acid (either 400 or 800 mcg per day, which was provided for six months to a year).[36],[37],[40],[41],[42],[43] In every study, folic acid supplementation improved the Full Scale IQ compared to the placebo. The increase in cognitive performance was associated with a reduction in homocysteine levels, confirming that folate produced a biochemical effect.[36],[37],[40] One study showed that a combination of folic acid and vitamin B12 was superior to either folic acid or B12 alone in improving cognition.[41]
The researchers also found that supplemental DHA (800 mg or 2 grams per day, for six months to two years) significantly improved cognitive function.[38],[39],[42],[43] Compared to the placebo groups, those who took DHA had lower circulating levels of beta-amyloid protein and a slowing of brain atrophy.[38],[39],[42]
Combined DHA and folate supplementation appeared to be more beneficial than either folate or DHA alone.
Combined DHA and folate supplementation appeared to be more beneficial in reducing beta-amyloid levels,[42] and slowing cognitive decline,[43] than either folate or DHA alone.
The benefits of dual supplementation with DHA and B vitamins have also been seen in European and Australian studies of individuals with mild cognitive impairment and elevated blood homocysteine levels.[44],[45],[46] B vitamin supplementation helped slow the rate of cognitive decline, but only when DHA levels were in the upper normal range.[45],[46] In patients with high levels of omega-3 fatty acids at baseline, B vitamins reduced the mean atrophy rate by 40% compared to placebo.[46]
Healthy diets support healthy aging
Vegetables, fruits, legumes, nuts, whole grains and fish, are considered the best foods for our brains.
Ideally, consuming a balanced diet containing a multitude of fresh foods including fish, vegetables, fruits, and nuts is the best way to meet our nutritional requirements.[47] Plant-based dietary patterns such as the Mediterranean diet, which includes plenty of vegetables, fruits, legumes, nuts, whole grains and fish, are considered the best for our brains and for overall health.[48],[49],[50],[51]
A buildup of beta-amyloid can begin decades before the clinical symptoms of Alzheimer’s disease become apparent, so it is important to consume enough omega-3s throughout life.[52],[53],[54],[55] Fish intake of equivalent to two four-ounce portions per week (eight ounces per week altogether) is associated with a 30% reduction in Alzheimer’s disease risk.[56]
Supplemental omega-3s, particularly DHA, may help fill in the gaps when fish intake is inadequate.[11],[57],[58] A 2021 review concludes that “individuals consuming higher amounts of long chain omega-3s are less likely to develop cognitive impairment, and it is most effective when dietary omega-3s are consumed prior to or in the early stages of cognitive decline.”[57]
As shown in clinical trials, B vitamins are also strongly linked with healthy aging. Healthy seniors who had daily helpings of leafy green vegetables, such as spinach and kale, exhibited a slower rate of cognitive decline, compared to those who tended to eat little or no greens.[34]
The use of a B vitamin supplement or a multivitamin and mineral supplement can help ensure sufficient folate as well as vitamin B12. “The compiled information supports the potential benefits of vitamin supplementation, especially relevant to the aging process and quality of life,” according to a 2021 review.[59]
Last but not least, there are significant associations between vitamin D deficiency and Alzheimer’s disease.[60],[61] Since vitamin D is also closely linked to immune support and healthy bones, and since most people do not get enough vitamin D, supplementation with this vitamin is strongly advised.
In sum, Alzheimer’s disease may be “the great morbidity of the 21st century,” but there is much we can do now to reduce its potential impact for ourselves and for family members. In addition to eating a balanced diet and continued physical activity, supplementing with DHA, B vitamins, and vitamin D, may further support cognitive health as we age.
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[30] Wolters M, et al. Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years. Eur J Nutr. 2005 Mar;44(3):183-92.
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[32] de S Moreira D, et al. Chronic mild hyperhomocysteinemia alters inflammatory and oxidative/nitrative status and causes protein/DNA damage, as well as ultrastructural changes in cerebral cortex: is acetylsalicylic acid neuroprotective? Neurotox Res. 2018 Apr;33(3):580-92.
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The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
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Marina MacDonald, MS, PhD
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