Written by Chrystal Moulton, Science Writer. In the amyloid negative group, polyunsaturated fatty acid intake was associated with a negative trend in visuospatial construction (P= 0.03), delayed memory (P= 0.01), and total RBANS scores (P= 0.01).

Previous clinical research has demonstrated the importance of B vitamins and omega-3 fatty acids in cognitive health¹. B vitamins support cognitive health by lowering homocysteine levels^2,3. Omega-3 fatty acids, specifically DHA, supports plasma membrane while reducing homocysteine levels⁴. Nutritional research has demonstrated some understanding of how specific dietary components effect brain health and cognition in elderly patients^5-7. In the current study, researchers investigated the effect of folate, B12, and polyunsaturated fatty acid intake on cognitive functioning of Alzheimer’s patients⁸.

Eligible participants were recruited from the Cognitive Health and Aging Register: Investigational Observational and Trial Studies in Dementia Research: Prospective Readiness Cohort Sub-study [CHARIOT-PRO]. Researchers screened 1,914 individuals between the age of 60 and 85 years old. Participants had to undergo a comprehensive medical, physical, and cognitive evaluation. Blood samples were also taken, and laboratory tests were conducted at baseline. PET scan of the brain was used to determine the presence of amyloid plaques. Cerebrospinal fluid samples were also collected to determine the presence of amyloid beta and other markers of Alzheimer’s disease. Nutritional assessment was conducted to determine each individual’s intake of vitamin B12, folate, polyunsaturated fatty acids, and the ratio of unsaturated fatty acids to saturated fatty acids. The Repeatable Battery for the Assessment of Neuropsychological Status [RBANS] was used to measure attention, delayed memory, immediate memory, language, and visuospatial construction. Higher scores indicated good cognitive function. Multi-regression analysis was used to assess any association between the intake of folate, B12, and polyunsaturated fatty acids and cognitive health.

Data from 321 participants who completed all questionnaires and assessments was included in this analysis. The average age of participants was 71.78 ±5.49 years old with about 48% female and 52% male. Female participants had higher serum levels of HDL, LDL, and vitamin B12 compared to male participants (P= 0.001). Male participants had significantly higher serum levels of creatinine (P= 0.001). However, no difference was observed in nutrient intake between male and female participants. The amyloid positive group was significantly older (P= 0.03), had more APOE 4 allele carriers (P = 0.001), and higher serum folate (P = 0.002) than the amyloid negative group. Researchers found that only education status was correlated to scores in attention, immediate memory, and total RBANS score (P <0.05). In the amyloid positive group, multi-regression analysis revealed that intake of polyunsaturated fatty acids was significantly associated with a higher total score on the RBANS (P= 0.03). However, polyunsaturated fatty acid and folic acid intake showed a negative non-significant trend with cognitive scores in the amyloid positive group. In the amyloid negative group, polyunsaturated fatty acid intake was associated with a negative trend in visuospatial construction (P= 0.03), delayed memory (P= 0.01), and total RBANS scores (P= 0.01). Polyunsaturated fatty acid intake and folate combined were significantly associated with higher scores in delayed memory, visual spatial construction, and total RBANS scores in the amyloid negative group as well (P <0.05). Vitamin B12 intake was associated with a positive trend in all areas of the RBANS test except attention in both amyloid beta positive and negative patients; however, these trends were non-significant. The combination of folate, B12, and polyunsaturated fatty acid on cognitive tests revealed a positive association in attention (P= 0.05) among patients who were amyloid negative. However, the combination of the three nutrients was negatively associated with delayed memory in the amyloid positive group (P= 0.02). When saturated fatty acid intake was included into the models, researchers observed an overall decrease in cognitive scores. Among female participants, unsaturated to saturated fatty acid ratio had a significant negative association with language (P= 0.05), delayed memory (P= 0.01) and total RBANS score (P= 0.01). In the unsaturated to saturated fatty acid model, folate intake was positively associated with language (P= 0.03) and total RBANS score (P = 0.04) in the amyloid positive group. In the amyloid negative group, the combination of B12 in the unsaturated to saturated fatty acid model was associated with higher language scores (P= 0.03).

Overall, this analysis demonstrated the effect of nutritional intake of B12, folate, and polyunsaturated fatty acid in cognitive health depends on an individual’s sex and amyloid status. The ratio of unsaturated to saturated fatty acid, however, can attenuate the effects of polyunsaturated fatty acids on cognitive health. The analysis showed that folate intake could benefit patients who were amyloid negative, while polyunsaturated fatty acid intake benefits individuals who are amyloid positive. However, B12 intake was associated with higher cognitive scores in both groups. Additional research will be needed to verify these findings.

Source: Zhao, Chuliang, Karen A. Abbott, Chinedu Udeh-Momoh, Geraint Price, Oliver JK Robinson, Sujin Kang, and Celeste A. de Jager Loots. “Associations Between B Vitamin Interactions with Polyunsaturated Fatty Acids and Cognitive Function Among Cognitively Healthy Older People as Modified by Amyloid Status and Sex.” Nutrients 17, no. 9 (2025): 1407.

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Click here to read the full text study.

Posted August 12, 2025.

Chrystal is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Chicago.

References:

1. van Soest APM, de Groot L, Witkamp RF, van Lent DM, Seshadri S, van de Rest O. Concurrent nutrient deficiencies are associated with dementia incidence. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. Jul 2024;20(7):4594-4601. doi:10.1002/alz.13884
2. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. Jan 20 2007;369(9557):208-16. doi:10.1016/s0140-6736(07)60109-3
3. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. Jun 2012;27(6):592-600. doi:10.1002/gps.2758
4. Smith AD, Jernerén F, Refsum H. ω-3 fatty acids and their interactions. Am J Clin Nutr. Apr 6 2021;113(4):775-778. doi:10.1093/ajcn/nqab013
5. Hill E, Goodwill AM, Gorelik A, Szoeke C. Diet and biomarkers of Alzheimer’s disease: a systematic review and meta-analysis. Neurobiol Aging. Apr 2019;76:45-52. doi:10.1016/j.neurobiolaging.2018.12.008
6. Barnard ND, Bunner AE, Agarwal U. Saturated and trans fats and dementia: a systematic review. Neurobiol Aging. Sep 2014;35 Suppl 2:S65-73. doi:10.1016/j.neurobiolaging.2014.02.030
7. Oikonomidi A, Lewczuk P, Kornhuber J, et al. Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta. J Neurochem. Oct 2016;139(2):324-332. doi:10.1111/jnc.13766
8. Zhao C, Abbott KA, Udeh-Momoh C, et al. Associations Between B Vitamin Interactions with Polyunsaturated Fatty Acids and Cognitive Function Among Cognitively Healthy Older People as Modified by Amyloid Status and Sex. Nutrients. Apr 23 2025;17(9)doi:10.3390/nu17091407