Nutrition and cognition
Relatively speaking, the brain consumes an immense amount of energy in comparison to the rest of the body. The mechanisms involved in the transfer of energy from foods to neurons are likely to be fundamental to the control of brain function. Human bodily processes, including the brain, all require both macronutrients, as well as micronutrients.
Insufficient intake of selected vitamins, or certain metabolic disorders, may affect cognitive processes by disrupting the nutrient-dependent processes within the body that are associated with the management of energy in neurons, which can subsequently affect synaptic plasticity, or the ability to encode new memories.
Nutrients needed for memory development
Choline is an essential nutrient and its primary function within the human body is the synthesis of cellular membranes, although it serves other functions as well. It is a precursor molecule to the neurotransmitter Acetylcholine which serves a wide range of functions including motor control and memory. Choline deficiencies may be related to some liver and neurological disorders. Because of its role in cellular synthesis, choline is an important nutrient during the prenatal and early postnatal development of offspring as it contributes to brain development. Choline intakes from food for men, women and children may be below the Adequate Intake levels. Women, especially when pregnant or lactating, the elderly, and infants, are at risk for choline deficiency. Beef liver, wheat germ, and egg yolks are common foods providing choline.
Lutein and Zeaxanthin
Lutein and zeaxanthin are carotenoids that contain very strong antioxidants. Most of the research thus far has focused on the effect that these carotenoids have on vision and increased processing speeds of the eye. In recent years, scientists have shifted their focus to their contribution to brain development and cognition due to newly found bio-accumulation of lutein and zeaxanthin in the brain. These nutrients can be found mostly in dark, leafy greens. Some other foods include eggs, broccoli, zucchini, corn, and brussels sprouts. These foods should be raw or steamed in order to get the most nutrients out of them.
Omega 3 fatty acids
Omega 3 fatty acids are essential for brain development and support cognition. These acids affect how the cell receptors react inside of the cell membranes. The human body is not able to make, or synthesize, omega 3 or DHA acids on its own. This means that the only source we have for these vital fatty acids comes directly form the food that we eat. Many studies have shown that people who consume larger amounts of fish in their diet are less likely to suffer from depression. Fish, especially salmon, have large amounts of omega 3 fatty acids and docosahexaonic acid (DHA). In the last 100 years, the western civilizations have shown a significant decrease in DHA and omega 3 intake, and increase in saturated and trans fats. Comparatively, locations like the United States and Germany have dramatically more cases of major depression than locations like Japan, where their main food source comes from their fishing industry.
Foods for healthy brain development in children
There are many foods that support healthy brain development. Many experts recommend fitting some of the following foods into your everyday diet:
Salmon is very high in omega 3 acids and DHA. There are other lean "white" fish meats, like albacore white tuna, that are a good source of protein but because they are more lean they are not high in fats. Salmon salad sandwiches, instead of tuna salad, will provide both protein and omega 3 fatty acids.
Aside from many other nutrients contained in flax seeds, just one tablespoon of flax seeds contains 1,597 mg of omega 3 fatty acids.
Blueberries and Strawberries
Many dark, rich colored berries are shown to improve memory.
Peanuts are a very good source of vitamin E which is an antioxidant. They also contains thiamin that helps support the brain and nervous systems. Nuts are also a very good source of protein for providing energy and increased concentration.
Whole Grains and Lean Beef
Whole grains provide a lot of glucose and fiber. The fiber from the grains helps to regulate the release of glucose into the body. Glucose sugars are used by your body for energy. Higher levels of energy are shown to improve concentration levels of the brain. Lean beef is an excellent source of iron which is also shown to provide energy levels and increase concentration. a
These types of foods are rich with antioxidants needed to cleanse the blood stream and help to keep brain cells strong.
Dairy foods provide the body with Vitamins B and D. Vitamin B is essential for brain tissue growth and also provides the body with enzymes.
Leafy greens such as collard greens, spinach, cabbage, romaine lettuce, and kale are a good source of folate and very rich in vitamins.
B-Vitamin deficiencies and cognition
B vitamins, also known as the B-complex, are an interrelated group of nutrients which often co-occur in food. The complex consists of: thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxin (B6), folic acid (B9), cobalamin (B12), and biotin. B vitamins are not synthesized in the body, and thus need to be obtained from food. B-complex vitamins are water-soluble vitamins, which means that they are not stored within the body. In consequence, the B vitamins need ongoing replenishment. It is possible to identify broad cognitive effects of certain B vitamins, as they are involved in many significant metabolic processes within the brain.
In a study done by a group of researchers in 2012, vitamin levels were measured in the subjects' blood and compared to the results from memory tests that they were given. The study showed that people with higher vitamin levels, mainly Vitamin B, had higher scores on their memory tests. The study was conducted at the Oregon Health & Science University and although it may still need official confirmation, there is sufficient evidence to support the fact that improving your diet can significantly increase the sharpness of your brain.
Vitamin B1 (thiamine)
This vitamin is important for the facilitation of glucose use, thus ensuring the production of energy for the brain, and normal functioning of the nervous system, muscles and heart. Thiamine is found throughout mammalian nervous tissue, including the brain and spinal cord. Metabolism and coenzyme function of the vitamin suggest a distinctive function for thiamine within the nervous system. The brain retains its thiamine content in the face of a vitamin-deficient diet with great tenacity, as it is the last of all nervous tissues studied to become depleted.
Lack of thiamin causes the disease known as beriberi. There are two forms of beriberi: "wet", and "dry". Dry beriberi is also known as cerebral beriberi and characterized by peripheral neuropathy. Thiamine deficiency has been reported in up to 80% of people who are alcoholic due to inadequate nutritional intake, reduced absorption, and impaired utilization of thiamine. Clinical signs of B1 deficiency include mental changes such as apathy, decrease in short-term memory, confusion, and irritability; also increased rates of depression, dementia, falls, and fractures in old age.
The lingering symptoms of neuropathy associated with cerebral beriberi are known as Korsakoff's syndrome, or the chronic phase of Wernicke-Korsakoff's. Wernicke encephalopathy is characterized by ocular abnormalities, ataxia of gait, a global state of confusion, and neuropathy. The state of confusion associated with Wernicke's may consist of apathy, inattention, spatial disorientation, inability to concentrate, and mental sluggishness or restlessness. Clinical diagnosis of Wernicke's disease cannot be made without evidence of ocular disturbance, yet these criteria may be too rigid. Korsakoff's syndrome likely represents a variation in the clinical manifestation of Wernicke encephalophathy, as they both share similar pathological origin. It is often characterized by confabulation, disorientation, and profound amnesia. Characteristics of the neuropathology are varied, but generally consist of bilaterally symmetrical midline lesions of brainstem areas, including the mammillary bodies, thalamus, periaqueductal region, hypothalamus, and the cerebellar vermis. Immediate treatment of Wernicke encephalopathy involves the administration of intravenous thiamine, followed with long-term treatment and prevention of the disorder through oral thiamine supplements, alcohol abstinence, and a balanced diet. Improvements in brain functioning of chronic alcoholics may occur with abstinence-related treatment, involving the discontinuation of alcohol consumption and improved nutrition.
Vitamin B3 (niacin)
Vitamin B3, also known as niacin, includes both nicotinamide as well as nicotinic acid, both of which function in many biological oxidization and reduction reactions within the body. Niacin is involved in the synthesis of fatty acids and cholesterol, known mediators of brain biochemistry, and in effect, of cognitive function. Pellagra is a niacin deficiency disease. Pellagra is classically characterized by four 4 "D's": diarrhea, dermatitis, dementia, and death. Neuropsychiatric manifestations of pellagra include headache, irritability, poor concentration, anxiety, hallucinations, stupor, apathy, psychomotor unrest, photophobia, tremor, ataxia, spastic paresis, fatigue, and depression. Symptoms of fatigue and insomnia may progress to encephalophathy characterized by confusion, memory loss, and psychosis. Those afflicted with pellagra may undergo pathological alterations in the nervous system. Findings may include demylenation and degeneration of various affected parts of the brain, spinal cord, and peripheral nerves.
Oral nicotinamide has been promoted as an over-the-counter drug for the treatment of Alzheimer's dementia. Conversely, no clinically significant effect has been found for the drug, as nicotinamide administration has not been found to promote memory functions in people with mild to moderate dementia of either Alzheimers', vascular, or fronto-temporal types. This evidence suggests that nicotinamide may treat dementia as related to pellegra, but administration does not effectively treat other types of dementia. Though treatment with niacin does little to alter the effects of Alzheimer's dementia, niacin intake from foods is inversely associated with the disease.
Vitamin B9 (folic acid)
Folate and vitamin B12 play a vital role in the synthesis of S-adenosylmethionine, which is of key importance in the maintenance and repair of all cells, including neurons. In addition, folate has been linked to the maintenance of adequate brain levels of cofactors necessary for chemicals reactions that lead to the synthesis of serotonin and catecholamine neurotransmitters. Concentrations of blood plasma folate and homocysteine concentrations are inversely related, such that an increase in dietary folate decreases homocysteine concentration. Thus, dietary intake of folate is a major determinant of homocysteine levels within the body. The relationship between folate and B12 is so interdependent that deficiency in either vitamin can result in megaloblastic anemia, characterized by organic mental change.
The link between levels of folate and altered mental function is not large, but is sufficient enough to suggest a causal association. Deficiency in folate can cause an elevation of homocysteine within the blood, as the clearance of homocysteine requires enzymatic action dependent on folate, and to a lesser extent, vitamins B6 and B12. Elevated homocysteine has been associated with increased risk of vascular events, as well as dementia.
Differences lie in the presentation of megaloblastic anemia induced by either folate or B12 deficiency. Megaloblastic anemia related to deficiency in B12 generally results in peripheral neuropathy, whereas folate-related anemia often results in affective, or mood disorders. Neurological effects are not often associated with folate-related megaloblastic anemia, although demyelinating disorders may eventually present. In one study, mood disturbances were recorded for the majority of people with megaloblastic anemia in the absence of B12 deficiency. In addition, folate concentrations within blood plasma have been found to be lower in people with both unipolar and bipolar depressive disorders when compared with control groups. In addition, depressive groups with low folate concentrations responded less well to standard antidepressant therapy than did those with normal levels within plasma. However, replication of these findings are less robust.
Intake of the vitamin has been linked to deficits in learning and memory, particularly within the elderly population. Elderly people deficient in folate may present with deficits in free recall and recognition, which suggests that levels of folate may be related to efficacy of episodic memory. Lack of adequate folate may produce a form of dementia considered to be reversible with administration of the vitamin. Indeed, there is a degree of improvement in memory associated with folate treatment. In a 3-year longitudinal study of men and women aged 50–70 years with elevated homocysteine plasma concentration, researchers found that a daily oral folic acid supplementation of 800μg resulted in an increase in folate levels and a decrease in homocysteine levels within blood plasma. In addition to these results, improvements of memory, and information-processing speed, as well as slight improvements of sensorimotor speed were observed, which suggests there is a link between homocysteine and cognitive performance. However, while the amount of cognitive improvement after treatment with folate is correlated with the severity of folate deficiency, the severity of cognitive decline is independent of the severity of folate deficiency. This suggests that the dementia observed may not be entirely related to levels folate, as there could be additional factors that were not accounted for which might have an effect.
Because neurulation may be completed before pregnancy is recognized, it is recommended that women capable of becoming pregnant take about 400μg of folic acid from fortified foods, supplements, or a combination of the two in order to reduce the risk of neural tube defects. These major anomalies in the nervous system can be reduced by 85% with systematic folate supplementation occurring before the onset of pregnancy. The incidence of Alzheimer's and other cognitive diseases has been loosely connected to deficiencies in folate. It is recommended for the elderly to consume folate through food, fortified or not, and supplements in order to reduce risk of developing the disease.
Vitamin B12 (cobalamin)
Also known as cobalamin, B12 is important for the maintenance of neurological function and psychiatric health. B12 deficiency, also known as hypocobalaminemia, often results from complications involving absorption into the body. An assortment of neurological effects can be observed in 75–90% of individuals of any age with clinically observable B12 deficiency. Cobalamin deficiency manifestations are apparent in the abnormalities of the spinal cord, peripheral nerves, optic nerves, and cerebrum. These abnormalities involve a progressive degeneration of myelin, and may be expressed behaviorally through reports of sensory disturbances in the extremities, or motor disturbances, such as gait ataxia. Combined myelopathy and neuropathy are prevalent within a large percentage of cases. Cognitive changes may range from loss of concentration to memory loss, disorientation, and dementia. All of these symptoms may present with or without additional mood changes. Mental symptoms are extremely variable, and include mild disorders of mood, mental slowness, and memory defect. Memory defect encompasses symptoms of confusion, severe agitation and depression, delusions and paranoid behavior, visual and auditory hallucinations, dysphasia, violent maniacal behavior and epilepsy. It has been suggested that mental symptoms could be related to a decrease in cerebral metabolism, as caused by the state of deficiency.
Mild to moderate cases of pernicious anemia may show poor concentration. In severe cases of pernicious anemia, individuals may present with various cognitive problems such as dementia, and memory loss. It is not always easy to determine whether B12 deficiency is present, especially within older adults. People may present with violent behavior or more subtle personality changes. They may also present with vague complaints, such as fatigue or memory loss, that may be attributed to normative aging processes. Cognitive symptoms may mimic behavior in Alzheimer's and other dementias as well.
People who are deficient in B12 despite normal absorption functionality may be treated through oral administration of at least 6 µg/day of the vitamin in pill form. People who suffer from irreversible causes of deficiency, such as pernicious anemia or old age, will need lifelong treatment with pharmacological doses of B12. Strategy for treatment is dependent on the person's level of deficiency as well as their level of cognitive functioning. Treatment for those with severe deficiency involves 1000 µg of B12 administered intramuscularly daily for one week, weekly for one month, then monthly for the rest of the person's life. The progression of neurological manifestations of cobalamin deficiency is generally gradual. As a result, early diagnosis is important or else irreversible damage may occur. People who become demented usually show little to no cognitive improvement with the administration of B12. There is risk that folic acid administered to those with B12 deficiency may mask anemic symptoms without solving the issue at hand. In this case, peoplewould still be at risk for neurological deficits associated with B12 deficiency-related anemia, which are not associated with anemia related to folate deficiency.
Vitamin A deficiency and impaired memory
Vitamin A is an essential nutrient for mammals which takes form in either retinol or the provitamin beta-Carotene. It helps regulation of cell division, cell function, genetic regulation, helps enhance the immune system, and is required for brain function, chemical balance, growth and development of the central nervous system and vision.
Aging and cognitive disease
Foods that are rich in omega-3 fatty acids have been shown to decrease risk of getting Alzheimer's disease. Omega-3 fatty acids, primarily docosahexaenoic acid (DHA), which is the most prevalent omega-3 fatty acid found in neurons, have been studied extensively for use in possible prevention and therapy of Alzheimer's disease. Some studies (cross-sectional) suggest that reduced intake or low brain levels of DHA are associated with earlier development of cognitive deficits or development of dementia, including Alzheimer's disease. Several clinical trials suggest that omega-3 fatty acid supplementation does not have significant effects in the treatment of Alzheimer's disease—which in turn may suggest that the protective benefits of omega-3 fatty acid supplementation could depend on the scope of the disease and other confounding factors. A diet that is rich in antioxidants will also help get rid of free radicals in the body, which could be a cause for Alzheimer's. The buildup of Beta Amyloid plaques, a marker highly associated with Alzheimer's disease, generates cell damaging free radicals. Therefore, the role of antioxidants as protectants against Alzheimer's disease has become a hot topic of study. Simple dietary modification, towards fewer highly processed carbohydrates and relatively more fats ad cholesterol, is likely a protective measure against Alzheimer's disease.
Additionally, folic acid has also been found to improve the memory of older people. There is some evidence that deficiency in folic acid may increase the risk of dementia, especially Alzheimer's disease and vascular dementia, but there is debate about whether it lowers risk of cognitive impairment in the older population. Folic acid supplementation is shown to lower blood homocysteine levels, while folic acid deficiency can lead to a condition of high levels of homocysteine (Hcy) in the bloodstream called hyperhomocysteinemia (HHcy). HHcy is related to several vascular diseases such as coronary artery disease, peripheral vascular disease, and stroke.
- Gómez-Pinilla, Fernando (2008). "Brain foods: The effects of nutrients on brain function". Nature Reviews Neuroscience. 9 (7): 568–78. doi:10.1038/nrn2421. PMC 2805706. PMID 18568016.
- Bourre, JM (2006). "Effects of nutrients (in food) on the structure and function of the nervous system: Update on dietary requirements for brain. Part 1: Micronutrients". The Journal of Nutrition, Health & Aging. 10 (5): 377–85. PMID 17066209.
- "Choline". Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 1 January 2015. Retrieved 22 October 2019.
- Zeisel, Steven H; Da Costa, Kerry-Ann (2009). "Choline: An essential nutrient for public health". Nutrition Reviews. 67 (11): 615–23. doi:10.1111/j.1753-4887.2009.00246.x. PMC 2782876. PMID 19906248.
- Zeisel, Steven H; Da Costa, Kerry-Ann (2009). "Choline: An essential nutrient for public health". Nutrition Reviews. 67 (11): 615–23. doi:10.1111/j.1753-4887.2009.00246.x. PMC 2782876. PMID 19906248.
- Foods and Raw Materials. Kemerovo State University. 2018. doi:10.12737/issn.2308-4057.
- Gómez-Pinilla, Fernando (July 2008). "Brain foods: the effects of nutrients on brain function". Nature Reviews. Neuroscience. 9 (7): 568–578. doi:10.1038/nrn2421. ISSN 1471-003X. PMC 2805706. PMID 18568016.
- Davis, Jeanie Lerche. "Top 10 Brain Foods for Children". WebMD. Retrieved 2019-10-22.
- "11 Best Foods to Boost Your Brain and Memory". Healthline. 9 May 2017. Retrieved 2019-10-22.
- Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (PDF). Washington, DC: National Academy Press. 1998. ISBN 978-0-309-06554-2. Archived from the original (PDF) on 2015-09-06. Retrieved 2012-03-21.[page needed]
- Thompson, J (2005). "Vitamins, minerals and supplements: Part two". Community Practitioner. 78 (10): 366–8. PMID 16245676.
- Cooper, Jack R.; Pincus, Jonathan H. (1979). "The role of thiamine in nervous tissue". Neurochemical Research. 4 (2): 223–39. doi:10.1007/BF00964146. PMID 37452. S2CID 22390486.
- Bond, Nigel W.; Homewood, Judi (1991). "Wernicke's encephalopathy and Korsakoff's psychosis: To fortify or not to fortify?". Neurotoxicology and Teratology. 13 (4): 353–5. doi:10.1016/0892-0362(91)90083-9. PMID 1921914.
- Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (PDF). Washington, DC: National Academy Press. 1998. ISBN 978-0-309-06554-2. Archived from the original (PDF) on 2013-06-18. Retrieved 2012-03-21.[page needed]
- Hoyumpa, Anastacio M. (1983). "Alcohol and Thiamine Metabolism". Alcoholism: Clinical and Experimental Research. 7 (1): 11–14. doi:10.1111/j.1530-0277.1983.tb05403.x. PMID 6342440.
- Singleton., C.K.; Martin, P.R. (2001). "Molecular Mechanisms of Thiamine Utilization". Current Molecular Medicine. 1 (2): 197–207. doi:10.2174/1566524013363870. PMID 11899071.
- Harper, C (1979). "Wernicke's encephalopathy: A more common disease than realised. A neuropathological study of 51 cases". Journal of Neurology, Neurosurgery & Psychiatry. 42 (3): 226–31. doi:10.1136/jnnp.42.3.226. PMC 490724. PMID 438830.
- Ogershok, Paul R.; Rahman, Aamer; Nestor, Scott; Brick, James (2002). "Wernicke Encephalopathy in Nonalcoholic Patients". American Journal of the Medical Sciences. 323 (2): 107–11. doi:10.1097/00000441-200202000-00010. PMID 11863078. S2CID 12996092.
- Harper, C G; Giles, M; Finlay-Jones, R (1986). "Clinical signs in the Wernicke-Korsakoff complex: A retrospective analysis of 131 cases diagnosed at necropsy". Journal of Neurology, Neurosurgery & Psychiatry. 49 (4): 341–5. doi:10.1136/jnnp.49.4.341. PMC 1028756. PMID 3701343.
- Yehuda, Shlomo; Rabinovitz, Sharon; Mostofsky, David I. (1999). "Essential fatty acids are mediators of brain biochemistry and cognitive functions". Journal of Neuroscience Research. 56 (6): 565–70. doi:10.1002/(SICI)1097-4547(19990615)56:6<565::AID-JNR2>3.0.CO;2-H. PMID 10374811.
- Zimmerman, HM (1939). "The Pathology of the Nervous System in Vitamin Deficiencies". The Yale Journal of Biology and Medicine. 12 (1): 23–28.7. PMC 2602501. PMID 21433862.
- Rainer, M.; Kraxberger, E.; Haushofer, M.; Mucke, H. A. M.; Jellinger, K. A. (2000). "No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia". Journal of Neural Transmission. 107 (12): 1475–81. doi:10.1007/s007020070011. PMID 11459000. S2CID 22789552.
- Morris, M C (2004). "Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline". Journal of Neurology, Neurosurgery & Psychiatry. 75 (8): 1093–1099. doi:10.1136/jnnp.2003.025858. PMC 1739176. PMID 15258207.
- Hauck, MR (1991). "Cognitive abilities of preschool children: Implications for nurses working with young children". Journal of Pediatric Nursing. 6 (4): 230–5. PMID 1865312.
- Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (PDF). Washington, DC: National Academy Press. 1998. ISBN 978-0-309-06554-2. Archived from the original (PDF) on 2013-05-15. Retrieved 2012-03-21.[page needed]
- Homocysteine Lowering Trialists' Collaboration (2005). "Dose-dependent effects of folic acid on blood concentrations of homocysteine: A meta-analysis of the randomized trials". The American Journal of Clinical Nutrition. 82 (4): 806–12. doi:10.1093/ajcn/82.4.806. PMID 16210710.
- Bottiglieri, T (1996). "Folate, vitamin B12, and neuropsychiatric disorders". Nutrition Reviews. 54 (12): 382–90. doi:10.1111/j.1753-4887.1996.tb03851.x. PMID 9155210.
- Quadri, P; Fragiacomo, C; Pezzati, R; Zanda, E; Forloni, G; Tettamanti, M; Lucca, U (2004). "Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia". The American Journal of Clinical Nutrition. 80 (1): 114–22. doi:10.1093/ajcn/80.1.114 (inactive 31 May 2021). PMID 15213037.CS1 maint: DOI inactive as of May 2021 (link)
- Shorvon, S D; Carney, M W; Chanarin, I; Reynolds, E H (1980). "The neuropsychiatry of megaloblastic anaemia". BMJ. 281 (6247): 1036–8. doi:10.1136/bmj.281.6247.1036. PMC 1714413. PMID 6253016.
- Bryan, J; Calvaresi, E; Hughes, D (2002). "Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages". The Journal of Nutrition. 132 (6): 1345–56. doi:10.1093/jn/132.6.1345. PMID 12042457.
- Wahlin, Åke; Hill, Robert D.; Winblad, Bengt; Bäckman, Lars (1996). "Effects of serum vitamin B-sub-1-sub-2 and folate status on episodic memory performance in very old age: A population-based study". Psychology and Aging. 11 (3): 487–96. doi:10.1037/0882-79184.108.40.2067. PMID 8893317.
- Durga, Jane; Van Boxtel, Martin PJ; Schouten, Evert G; Kok, Frans J; Jolles, Jelle; Katan, Martijn B; Verhoef, Petra (2007). "Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: A randomised, double blind, controlled trial". The Lancet (Submitted manuscript). 369 (9557): 208–216. doi:10.1016/S0140-6736(07)60109-3. PMID 17240287. S2CID 20395823.
- Fioravanti, M; Ferrario, E; Massaia, M; Cappa, G; Rivolta, G; Grossi, E; Buckley, AE (1998). "Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits". Archives of Gerontology and Geriatrics. 26 (1): 1–13. doi:10.1016/s0167-4943(97)00028-9. PMID 18653121.
- Moyers, S; Bailey, LB (2001). "Fetal malformations and folate metabolism: Review of recent evidence". Nutrition Reviews. 59 (7): 215–24. doi:10.1111/j.1753-4887.2001.tb07013.x. PMID 11475447.
- Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (PDF). Washington, DC: National Academy Press. 1998. ISBN 978-0-309-06554-2. Archived from the original (PDF) on 2012-09-12. Retrieved 2012-03-19.[page needed]
- Hvas, AM; Nexo, E (2006). "Diagnosis and treatment of vitamin B12 deficiency--an update". Haematologica. 91 (11): 1506–12. PMID 17043022.
- Holmes, J. M. (1956). "Cerebral Manifestations of Vitamin-B12 Deficiency". BMJ. 2 (5006): 1394–8. doi:10.1136/bmj.2.5006.1394. PMC 2035923. PMID 13374343.
- Malouf, Reem; Grimley Evans, John (2008-10-08). "Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people". The Cochrane Database of Systematic Reviews (4): CD004514. doi:10.1002/14651858.CD004514.pub2. ISSN 1469-493X. PMID 18843658.
- Vakhapova, Veronika; Cohen, Tzafra; Richter, Yael; Herzog, Yael; Korczyn, Amos D. (2010). "Phosphatidylserine Containing ω–3 Fatty Acids May Improve Memory Abilities in Non-Demented Elderly with Memory Complaints: A Double-Blind Placebo-Controlled Trial". Dementia and Geriatric Cognitive Disorders. 29 (5): 467–74. doi:10.1159/000310330. PMID 20523044. S2CID 34913305.
- Jicha, GA; Markesbery, WR (Apr 7, 2010). "Omega-3 fatty acids: potential role in the management of early Alzheimer's disease". Clinical Interventions in Aging. 5: 45–61. doi:10.2147/cia.s5231. PMC 2854051. PMID 20396634.
- Miranda S, Opazo C, Larrondo LF, Muñoz FJ, Ruiz F, Leighton F, Inestrosa NC (2000). "The role of oxidative stress in the toxicity induced by amyloid ß-peptide in Alzheimer's disease". Progress in Neurobiology. 62 (6): 633–648. doi:10.1016/S0301-0082(00)00015-0. hdl:10533/172411. PMID 10880853. S2CID 53185151.
- Berry, RJ; Carter, HK; Yang, Q (July 2007). "Cognitive impairment in older Americans in the age of folic acid fortification". The American Journal of Clinical Nutrition. 86 (1): 265–7, author reply 267–9. doi:10.1093/ajcn/86.1.265. PMID 17616791.
- Reynolds, EH (Jun 22, 2002). "Folic acid, ageing, depression, and dementia". BMJ (Clinical Research Ed.). 324 (7352): 1512–5. doi:10.1136/bmj.324.7352.1512. PMC 1123448. PMID 12077044.