Quality of dietary fat and risk of Alzheimer’s disease and dementia in adults aged ≥50 years: a systematic review

  • Bright I. Nwaru Krefting Research Centre University of Gothenburg, Sweden
  • Jutta Dierkes Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen; and Department of Laboratory Medicine and Pathology, Haukeland University Hospital, Bergen, Norway
  • Alfons Ramel Faculty of Food Science and Nutrition, University of Iceland, Iceland
  • Erik Kristoffer Arnesen Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
  • Birna Thorisdottir Faculty of Sociology, Anthropology and Folkloristics & Health Science Institute, University of Iceland, Reykjavik, Iceland
  • Christel Lamberg-Allardt Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
  • Fredrik Söderlund Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • Linnea Bärebring Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • Agneta Åkesson Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Keywords: Alzheimer’s disease, dementia, NNR, dietary fat


Objective: To identify, critically appraise, and synthesize evidence on the effect of quality of dietary fat intake and different classes of fatty acids on the risk of Alzheimer’s disease (AD) and dementia in adults aged ≥50 years.

Methods: We searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until May 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Classes of fatty acids included were saturated fatty acids (SFAs), trans fatty acids (TFAs), monounsaturated fatty acids (MUFAs), poly-unsaturated fatty acids (PUFAs), and their subtypes and sources. Given between-study heterogeneity, we did not perform meta-analyses but narratively described findings from the studies.

Results: From 4,491 identified records, five articles (based on four prospective cohort studies) met the inclusion criteria. Three studies had an overall serious risk of bias, while one study had a moderate risk. Overall, we found no robust association between intake of any fatty acids type and the development of AD and dementia. For example, for SFA and TFA, there was contradictory associations reported on AD: one study found that each unit increase in energy-adjusted intake of SFA (risk ratio [RR] 0.83, 95%CI 0.70–0.98) and TFA (RR 0.80, 95%CI 0.65–0.97) was associated with a decreased risk of AD, but not dementia. For PUFA, one study found that higher quintile intake of marine-based n-3 PUFA was associated with a decreased risk of AD. The intake of other fatty acids was not associated with the outcomes. The certainty of the overall evidence was inconclusive.

Conclusion: We found no clear association between the intake of various classes of fatty acids and the risk of AD and dementia in adults. More well-designed prospective studies are required to clarify these findings.


Download data is not yet available.


1. Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and Ad pathology. Neurobiol Aging 2004; 25: 641–50. doi: 10.1016/j.neurobiolaging.2003.12.023

2. Martins IJ, Hone E, Foster JK, Sunram-Lea SI, Gnjec A, Fuller SJ, et al. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer’s disease and cardiovascular disease. Mol Psych 2006; 11: 721–36. doi: 10.1038/sj.mp.4001854

3. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, et al. Dietary fats and the risk of incident Alzheimer disease. Arch Nuerol 2003; 60: 194–200. doi: 10.1001/archneur.60.2.194

4. Lindsay J, Laurin D, Verreault R, Hébert R, Helliwell B, Hill GB, et al. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 2002; 156: 445–53. doi: 10.1093/aje/kwf074

5. Podewills LJ, Guallart E, Kuller LH, Fried LP, Lopez OL, Carlson M, et al. Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. Am J Epidemiol 2005; 161: 639–51. doi: 10.1093/aje/kwi092

6. Rovio S, Kårehold I, Helkala E-L, Viitanen M, Winblad B, Tuomilehto J, et al. Leisure time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 2005; 4: 705–10. doi: 10.1016/S1474-4422(05)70198-8

7. Farer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer’s disease: a meta-analysis. JAMA 1997; 278: 1349–56. doi: 10.1001/jama.1997.03550160069041

8. Anttila T, Helkala E-L, Viitanen M, Kåreholt I, Fratiglioni L, Winblad B, et al. Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study: BMJ 2004; 329: 539–42. doi: 10.1136/bmj.38181.418958.BE

9. Kivipelto M, Helkala E-L, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and Alzheimer’s disease in later life. Longitudinal, population based study. BMJ 2001; 322: 1447–51. doi: 10.1136/bmj.322.7300.1447

10. Morris MC. The role of nutrition in Alzheimer’s disease: epidemiological evidence. Eur J Neurol 2009; 16(Suppl 1): 1–7. doi: 10.1111/j.1468-1331.2009.02735.x

11. Scarmeas N, Anastasiou CA, Yannakoulia M. Nutrition and prevention of cognitive impairment. Lancet Neurol 2018; 17: 1006–15. doi: 10.1016/S1474-4422(18)30338-7

12. Kamphuis PJ, Wurtman RJ. Nutrition and Alzheimer’s disease: preclinical concepts. Eur J Neurol 2009; 16(Suppl 1): 12–18. doi: 10.1111/j.1468-1331.2009.02737.x

13. Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009; 66: 216–25. doi: 10.1001/archneurol.2008.536

14. Kitajka K, Puskas LG, Zvara A, Hackler Jr L, Barceló-Coblijn G, Yeo YK, et al. The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Natl Acad Sci U S A 2002; 99: 2619–24. doi: 10.1073/pnas.042698699

15. Grimm MOW, Michaelson DM, Hartmann T. Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer’s disease: a rationale for multi-nutrient dementia prevention. J Lipid Res 2017; 58: 2083–101. doi: 10.1194/jlr.R076331

16. Blok WL, Katan MB, van der Meer JWM. Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. J Nutr 1996; 126: 1515–33. doi: 10.1093/jn/126.6.1515

17. Akiyama H, Barger S, Barnum S, Bradt B, Cole GM, Cooper NR, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging 2000; 21: 383–421. doi: 10.1016/S0197-4580(00)00124-X

18. Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – principles and methodologies. Food Nutr Res 2020; 64: 4402. doi: 10.29219/fnr.v64.4402

19. Høyer A, Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, et al. The Nordic nutrition recommendations 2022 – prioritisation of topics for de novo systematic reviews. Food Nutr Res 2021; 65: 7828. doi: 10.29219/fnr.v65.7828

20. Arnesen EK, Christensen JJ, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – handbook for systematic reviews. Food Nutr Res 2020; 64: 4404. doi: 10.29219/fnr.v64.4404

21. Arnesen EK, Christensen JJ, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – structure and rationale of systematic reviews. Food Nutr Res 2020; 64: 4403. doi: 10.29219/fnr.v64.4403

22. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71. doi: 10.1136/bmj.n71

23. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160. doi: 10.1136/bmj.n160

24. Nutrition Evidence Systematic Review. Risk of bias for nutrition observational studies (RoB-NObs) tool 2019. Available from: https://nesr.usda.gov/sites/default/files/2019-07/RiskOfBiasForNutritionObservationalStudies-RoB-NObs.pdf [cited 6 February 2020].

25. Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919. doi: 10.1136/bmj.i4919

26. Agency for Healthcare Research and Quality (AHRQ). Methods guide for effectiveness and comparative effectiveness reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2014.

27. Morton SC, Murad MH, O’Connor E, Lee CS, Booth M, Vandermeer BW, et al. Quantitative synthesis – an update. In: Methods guide for comparative effectiveness reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2018.

28. Deeks JJ, Higgins JPT, Altman DG. Analysing data and undertaking meta-analyses. In: Higgins JPT, Altman DG, eds. Cochrane handbook for systematic reviews of interventions, version 510. The Cochrane Collaboration; 2019. John Wiley & Sons Ltd. New Jersey, USA.

29. Engelhart MJ, Geerlings MI, Ruitenberg A, Van Swieten JC, Hofman A, Witteman JCM, et al. Diet and risk of dementia: does fat matter? The Rotterdam study. Neurol 2002; 59: 1915–21. doi: 10.1212/01.WNL.0000038345.77753.46

30. Gustafson DR, Bäckman K, Scarmaes N, Stern Y, Manly JJ, Mayeux R, et al. Dietary fatty acids and risk of Alzheimer’s disease and related dementias: observations from the Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP). Alzheimer’s Dement 2020; 16: 1638–49. doi: 10.1002/alz.12154

31. Kivipelto M, Rovio S, Ngandu T, Kåreholt I, Eskelinen M, Winblad B, et al. Apolipoprotein E ɛ4magnifies lifestyle risks for dementia: a population-based study. J Cell Mol Med 2008; 12: 2762–71. doi: 10.1111/j.1582-4934.2008.00296.x

32. Laitinen MH, Ngandu T, Rovio S, Hlkala E-L, Uusitalo U, Viitanen M, et al. Fat intake at midlife and risk of dementia and Alzheimer’s disease: a population-based study. Dement Geriatr Cogn Disord 2006; 22: 99–107. doi: 10.1159/000093478

33. Zhuang P, Zhang Y, He W, Chen X, Chen J, He L, et al. Dietary fats in relation to total and cause-specific mortality in a prospective cohort of 521,120 individuals with 16 years of follow-up. Circ Res 2019; 124: 757–68. doi: 10.1161/CIRCRESAHA.118.314038

34. Barnard ND, Bunner AE, Agarwal U. Saturated and trans fats and dementia: a systematic review. Neurobiol Aging 2014; 35: S65–73. doi: 10.1016/j.neurobiolaging.2014.02.030

35. Cao G-Y, Li M, Han L, Tayie F, Yao S-S, Huang Z, et al. Dietary fat intake and cognitive function among older populations: a systematic review and meta-analysis. J Prev Alzheimers Dis 2019; 6: 204–11. doi: 10.14283/jpad.2019.9

36. Mozaffarian D, Aro A, Willett WC. Health effects of trans-fatty acids: experimental and observational evidence. Eur J Clin Nutr 2009; 63: S5–21. doi: 10.1038/sj.ejcn.1602973

37. Ooi EM, Ng TW, Watts GF, Barrett PHR. Dietary fatty acids and lipoprotein metabolism: new insights and updates. Curr Opin Lipidol 2013; 24: 192–7. doi: 10.1097/MOL.0b013e3283613ba2

38. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med 2010; 7: e1000252. doi: 10.1371/journal.pmed.1000252

39. Nagpal T, Sahu JK, Khare SK, Bashir K, Kulsum J. Trans fatty acids in food: a review on dietary intake, health impact, regulations and alternatives. J Food Sci 2021; 86: 5159–74. doi: 10.1111/1750-3841.15977
How to Cite
Nwaru B. I., Dierkes J., Ramel A., Arnesen E. K., Thorisdottir B., Lamberg-Allardt C., Söderlund F., Bärebring L., & Åkesson A. (2022). Quality of dietary fat and risk of Alzheimer’s disease and dementia in adults aged ≥50 years: a systematic review. Food & Nutrition Research, 66. https://doi.org/10.29219/fnr.v66.8629
Nordic Nutrition Recommendations 2022

Most read articles by the same author(s)