Read Time 5 Minutes
As life expectancy lengthens for most of the world, the incidence of dementia and cognitive decline is also increasing. The number of people affected by dementia is growing exponentially, with an estimated 55 million people diagnosed worldwide today and 139 million predicted to be diagnosed by 2050.1 In the United States, an estimated 6.07 million adults 65 years or older were living with clinical Alzheimer’s Disease in 2020,2 and US-based studies continue to report a disproportionate burden of dementia and mild cognitive impairment among older Black and Hispanic adults.2,3
Age-related cognitive decline may be a health concern for some patients, especially those with a family history or increased genetic risk for neurodegenerative disease. Multi-pronged lifestyle interventions offer promise for the prevention and delay of cognitive decline.4,5 For example, personalized dietary plans that include neuroprotective foods provide nutrients for optimal cognitive functioning and potentially reduce neuroinflammation, as well as improve brain plasticity.6,7
Nutrition is a key modulator of cognitive health, but what are those specific nutrients and vitamins that support cognition and reduce neurodegeneration? An important consideration is mitochondrial health. Age-related neurodegeneration has been associated with oxidative stress, flawed energy metabolism, and mitochondrial dysfunctions.8,9 In animal studies, a variety of vitamins and nutrients have demonstrated protective effects on mitochondria, including coenzyme Q10 (CoQ10),10 acetyl-L-carnitine (ALC),11 and resveratrol.11 And clinical studies have also suggested a role for ALC and resveratrol in the potential delay of cognitive decline.12,13 The coenzyme nicotinamide adenine dinucleotide (NAD) also influences many key cellular functions, including processes that are critical for maintaining metabolic homeostasis and for healthy aging.14 In the following video, IFM educator Robert Rountree, MD, explores the latest research on this coenzyme:
Whole Diet Approaches for Cognitive and Brain Health
Nutrient-dense anti-inflammatory diets have been associated with reduced risk of many chronic diseases.15 Research has also shown that healthy nutrition habits, including diets that are high in phytochemicals and antioxidants, may be neuroprotective, may support cognition, and may even slow neurodegeneration.16,17
Epidemiological and observational studies, as well as clinical trials, continue to demonstrate that higher adherence to specific diets that prioritize plant, whole grain, and healthy fat intake, such as the Mediterranean, DASH (Dietary Approaches to Stop Hypertension), and MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diets, is associated with less cognitive decline and reduced risk of dementias such as Alzheimer’s disease.18-25 For example, a 2021 observational study used questionnaires to evaluate the effect of Mediterranean diet adherence on the cognitive abilities and psychological state of 2,092 men and women (65 years or older) from seven different Greek cities.19 Results from the study indicated that higher diet adherence was significantly associated with both better cognitive status and less depression symptoms.19 In addition, a 2022 meta-analysis of 26 cohort studies found that higher adherence to the Mediterranean diet was associated with a lower risk of mild cognitive impairment (RR=0.75; CI: 0.66-0.86) and Alzheimer’s disease (RR=0.71; CI: 0.56-0.89) among healthy adults.17
Brain Structure & Function
In addition to affecting cognitive scores, nutrition also affects underlying brain structures. As one example, polyphenols in foods have anti-inflammatory effects on microglia.26 Further, poor nutrition, such as consuming a Western diet, has been correlated with reduced hippocampal volume27 while intake of fish oil has been suggested to exert beneficial effects on white matter microstructural integrity and gray matter volume.28 A 2022 observational study (n=1,412 older adults followed for a median of 9.7 years) found that higher adherence to a MIND diet was associated with lower dementia risk and with preserved white matter microstructure.29 In addition, a first-of-its-kind systematic review published in 2020 evaluated 14 cross-sectional and longitudinal studies that measured dietary patterns, neuroimaging correlates, and neurocognitive tests.30 Most of the included studies assessed adherence to the Mediterranean diet, and the following are some of the review’s results:30
- Higher adherence to the Mediterranean diet correlated with larger total and regional brain volumes and higher white matter integrity.
- High adherence to the diet was associated with lower diffusivity (markers of microstructural changes) and in turn was associated with higher cognitive scores.
- Low adherence to the diet was associated with increased beta-amyloid in the left frontal-parietal cortex.
- Total gray matter volume was positively associated with the Mediterranean diet as well as fish consumption and negatively associated with other meat intake. Total white matter volume was positively linked with the Mediterranean diet.
- Overall, the Mediterranean diet and other assessed nutrient patterns (such as intake of vitamins, antioxidants, and fiber) were associated with white matter integrity, functional connectivity, total and regional brain volumes, and glucose metabolism.
THE ROLE OF THE GUT microbiota
The effectiveness of dietary approaches that protect against age-related cognitive decline may be linked to modulation of the gut microbiota structure and function.16,31 An optimal gut microbiome potentially improves the function of an aging brain,32 but research on specific possible mechanisms is limited,33 and some studies have shown neutral results. A 2020 randomized controlled trial investigated the association between diet, intestinal microbiota, and cognition in 226 healthy adults.34 Dietary intake, cognitive functioning, and fecal samples were assessed. Plant-rich diets were positively correlated with anti-inflammatory microbial species, and animal product–rich diets were associated with a pro-inflammatory microbial profile; however, no association was found between cognition and microbiota composition.34 Research continues to explore the associations between neuroinflammation and gut dysbiosis and what role any alterations in the gut microbiota may play in cognitive health and prevention of neurodegeneration.35
Clinical understanding of how nutrition and lifestyle factors support cognition and optimal brain function continues to evolve.36 Learn more about tools and strategies to help patients achieve sustainable lifestyle change and improve their well-being through IFM’s new course Lifestyle: The Foundations of Functional Medicine.
- World Health Organization. Dementia. Published September 20, 2022. Accessed October 25, 2022. https://www.who.int/news-room/fact-sheets/detail/dementia
- Rajan KB, Weuve J, Barnes LL, McAninch EA, Wilson RS, Evans DA. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in the United States (2020-2060). Alzheimers Dement. 2021;17(12):1966-1975. doi:1002/alz.12362
- 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. Published online October 24, 2022. doi:1001/jamaneurol.2022.3543
- Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the LancetLancet. 2020;396(10248):413-446. doi:10.1016/S0140-6736(20)30367-6
- Mamalaki E, Charisis S, Anastasiou CA, et al. The longitudinal association of lifestyle with cognitive health and dementia risk: findings from the HELIAD study. Nutrients. 2022;14(14):2818. doi:3390/nu14142818
- Poulose SM, Miller MG, Scott T, Shukitt-Hale B. Nutritional factors affecting adult neurogenesis and cognitive function. Adv Nutr. 2017;8(6):804-811. doi:3945/an.117.016261
- Di Majo D, Cacciabaudo F, Accardi G, et al. Ketogenic and modified Mediterranean diet as a tool to counteract neuroinflammation in multiple sclerosis: nutritional suggestions. Nutrients. 2022;14(12):2384. doi:3390/nu14122384
- Belenguer P, Duarte JMN, Schuck PF, Ferreira GC. Mitochondria and the brain: bioenergetics and beyond. Neurotox Res. 2019;36(2):219-238. doi:1007/s12640-019-00061-7
- Lejri I, Agapouda A, Grimm A, Eckert A. Mitochondria- and oxidative stress-targeting substances in cognitive decline-related disorders: from molecular mechanisms to clinical evidence. Oxid Med Cell Longev. 2019;2019:9695412. doi:1155/2019/9695412
- Sandhir R, Sethi N, Aggarwal A, Khera A. Coenzyme Q10 treatment ameliorates cognitive deficits by modulating mitochondrial functions in surgically induced menopause. Neurochem Int. 2014;74:16-23. doi:1016/j.neuint.2014.04.011
- Fišar Z, Hroudová J, Singh N, Koprivová A, Macecková D. Effect of simvastatin, coenzyme Q10, resveratrol, acetylcysteine and acetylcarnitine on mitochondrial respiration. Folia Biol (Praha). 2016;62(2):53-66.
- Pennisi M, Lanza G, Cantone M, et al. Acetyl-L-carnitine in dementia and other cognitive disorders: a critical update. Nutrients. 2020;12(5):1389. doi:3390/nu12051389
- Evans HM, Howe PR, Wong RH. Effects of resveratrol on cognitive performance, mood and cerebrovascular function in post-menopausal women; a 14-week randomised placebo-controlled intervention trial. Nutrients. 2017;9(1):27. doi:3390/nu9010027
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. doi:1038/s41580-020-00313-x
- Schulze MB, Martínez-González MA, Fung TT, Lichtenstein AH, Forouhi NG. Food based dietary patterns and chronic disease prevention. BMJ. 2018;361:k2396. doi:1136/bmj.k2396
- Angeloni C, Businaro R, Vauzour D. The role of diet in preventing and reducing cognitive decline. Curr Opin Psychiatry. 2020;33(4):432-438. doi:1097/YCO.0000000000000605
- Fu J, Tan LJ, Lee JE, Shin S. Association between the Mediterranean diet and cognitive health among healthy adults: a systematic review and meta-analysis. Front Nutr. 2022;9:946361. doi:3389/fnut.2022.946361
- van den Brink AC, Brouwer-Brolsma EM, Berendsen AAM, van de Rest O. The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets are associated with less cognitive decline and a lower risk of Alzheimer’s disease—a review. Adv Nutr. 2019;10(6):1040-1065. doi:1093/advances/nmz054
- Mantzorou M, Vadikolias K, Pavlidou E, et al. Mediterranean diet adherence is associated with better cognitive status and less depressive symptoms in a Greek elderly population. Aging Clin Exp Res. 2021;33(4):1033-1040. doi:1007/s40520-020-01608-x
- Barbaresko J, Lellmann AW, Schmidt A, et al. Dietary factors and neurodegenerative disorders: an umbrella review of meta-analyses of prospective studies. Adv Nutr. 2020;11(5):1161-1173. doi:1093/advances/nmaa053
- Troesch B, Eggersdorfer M, Laviano A, et al. Expert opinion on benefits of long-chain omega-3 fatty acids (DHA and EPA) in aging and clinical nutrition. Nutrients. 2020;12(9):2555. doi:3390/nu12092555
- Moustafa B, Trifan G, Isasi CR, et al. Association of Mediterranean diet with cognitive decline among diverse Hispanic or Latino adults from the Hispanic Community Health Study/Study of Latinos. JAMA Netw Open. 2022;5(7):e2221982. doi:1001/jamanetworkopen.2022.21982
- Deng Y, Rong S, Cheng G, et al. Association between adherence to three healthy dietary patterns and risk of cognitive disorders: meta-analysis. Wei Sheng Yan Jiu. 2022;51(5):725-732. doi:19813/j.cnki.weishengyanjiu.2022.05.009
- Gauci S, Young LM, Arnoldy L, Lassemillante AC, Scholey A, Pipingas A. Dietary patterns in middle age: effects on concurrent neurocognition and risk of age-related cognitive decline. Nutr Rev. 2022;80(5):1129-1159. doi:1093/nutrit/nuab047
- Andreu-Reinón ME, Chirlaque MD, Gavrila D, et al. Mediterranean diet and risk of dementia and Alzheimer’s disease in the EPIC-Spain Dementia Cohort Study. Nutrients. 2021;13(2):700. doi:3390/nu13020700
- Peña-Altamira E, Petralla S, Massenzio F, Virgili M, Bolognesi ML, Monti B. Nutritional and pharmacological strategies to regulate microglial polarization in cognitive aging and Alzheimer’s disease. Front Aging Neurosci. 2017;9:175. doi:3389/fnagi.2017.00175
- Jacka FN, Cherbuin N, Anstey KJ, Sachdev P, Butterworth P. Western diet is associated with a smaller hippocampus: a longitudinal investigation. BMC Med. 2015;13:215. doi:1186/s12916-015-0461-x
- Witte AV, Kerti L, Hermannstädter HM, et al. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014;24(11):3059-3068. doi:1093/cercor/bht163
- Thomas A, Lefèvre-Arbogast S, Féart C, et al. Association of a MIND Diet with brain structure and dementia in a French population. J Prev Alzheimers Dis. 2022;9(4):655-664. doi:14283/jpad.2022.67
- Rodrigues B, Asamane EA, Magalhães R, Sousa N, Thompson JL, Santos NC. The association of dietary patterns with cognition through the lens of neuroimaging—a systematic review. Ageing Res Rev. 2020;63:101145. doi:1016/j.arr.2020.101145
- Solch RJ, Aigbogun JO, Voyiadjis AG, et al. Mediterranean diet adherence, gut microbiota, and Alzheimer’s or Parkinson’s disease risk: a systematic review. J Neurol Sci. 2022;434:120166. doi:1016/j.jns.2022.120166
- Flanagan E, Lamport D, Brennan L, et al. Nutrition and the ageing brain: moving towards clinical applications. Ageing Res Rev. 2020;62:101079. doi:1016/j.arr.2020.101079
- González Olmo BM, Butler MJ, Barrientos RM. Evolution of the human diet and its impact on gut microbiota, immune responses, and brain health. Nutrients. 2021;13(1):196. doi:3390/nu13010196
- van Soest APM, Hermes GDA, Berendsen AAM, et al. Associations between pro- and anti-inflammatory gastro-intestinal microbiota, diet, and cognitive functioning in Dutch healthy older adults: the NU-AGE study. Nutrients. 2020;12(11):3471. doi:3390/nu12113471
- Leblhuber F, Ehrlich D, Steiner K, et al. The immunopathogenesis of Alzheimer’s disease is related to the composition of gut microbiota. Nutrients. 2021;13(2):361. doi:3390/nu13020361
- Kouvari M, D’Cunha NM, Travica N, et al. Metabolic syndrome, cognitive impairment and the role of diet: a narrative review. Nutrients. 2022;14(2):333. doi:3390/nu14020333