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Fish oil supplementation increases event-related posterior cingulate activation in older adults with subjective memory impairment

  • Published:
The journal of nutrition, health & aging

Abstract

Objective

To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment.

Design

Randomized, double-blind, placebo-controlled study.

Setting

Academic medical center.

Participants

Healthy older adults (62–80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia.

Intervention

Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks.

Measurements

Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI).

Results

At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p≤0.0001) but not placebo (−17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition.

Conclusions

Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

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References

  1. Imtiaz B, Tolppanen AM, Kivipelto M, Soininen H. Future directions in Alzheimer’s disease from risk factors to prevention. Biochem Pharmacol. 2014;88:661–670.

    Article  CAS  PubMed  Google Scholar 

  2. Solomon A, Mangialasche F, Richard E, Andrieu S, Bennett DA, Breteler M, Fratiglioni L, Hooshmand B, Khachaturian AS, Schneider LS, Skoog I, Kivipelto M. Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med. 2014;275:229–250.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Jessen F, Wiese B, Bachmann C, Eifflaender-Gorfer S, Haller F, Kölsch H, Luck T, Mösch E, van den Bussche H, Wagner M, Wollny A, Zimmermann T, Pentzek M, Riedel-Heller SG, Romberg HP, Weyerer S, Kaduszkiewicz H, Maier W, Bickel H. Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment. Arch Gen Psychiatry. 2010;67:414–422.

    Article  PubMed  Google Scholar 

  4. Rönnlund M, Sundström A, Adolfsson R, Nilsson LG. Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance: Evidence from the Betula prospective cohort study. Alzheimers Dement. [Epub ahead of print]. 2015 5.

    Google Scholar 

  5. Waldorff FB, Siersma V, Vogel A, Waldemar G. Subjective memory complaints in general practice predicts future dementia: a 4-year follow-up study. Int J Geriatr Psychiatry. 2012;27:1180–1188.

    Article  PubMed  Google Scholar 

  6. Meiberth D, Scheef L, Wolfsgruber S, Boecker H, Block W, Träber F, Erk S, Heneka MT, Jacobi H, Spottke A, Walter H, Wagner M, Hu X, Jessen F. Cortical thinning in individuals with subjective memory impairment. J Alzheimers Dis. 2015;45:139–146.

    PubMed  Google Scholar 

  7. Saykin AJ, Wishart HA, Rabin LA, Santulli RB, Flashman LA, West JD, Mc Hugh TL, Mamourian AC. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology. 2006;67:834–842.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Schultz SA, Oh JM, Koscik RL, Dowling NM, Gallagher CL, Carlsson CM, Bendlin BB, La Rue A, Hermann BP, Rowley HA, Asthana S, Sager MA, Johnson SC, Okonkwo OC. Subjective memory complaints, cortical thinning, and cognitive dysfunction in middle-aged adults at risk for AD. Alzheimers Dement (Amst). 2015;1:33–40.

    PubMed  Google Scholar 

  9. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR et al. Toward defining the preclinical stages of Alzheimer’s disease. Alzheimers Dementia, 2011;7:280–292.

    Article  Google Scholar 

  10. Lista S, Dubois B, Hampel H. Paths to Alzheimer’s disease prevention: from modifiable risk factors to biomarker enrichment strategies. J Nutr Health Aging. 2015;19:154–163.

    Article  CAS  PubMed  Google Scholar 

  11. Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alpérovitch A. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology. 2007;69:1921–1930.

    Article  CAS  PubMed  Google Scholar 

  12. Heude B, Ducimetière P, Berr C; EVA Study. Cognitive decline and fatty acid composition of erythrocyte membranes—The EVA Study. Am J Clin Nutr. 2003;77:803–808.

    CAS  PubMed  Google Scholar 

  13. Kalmijn S, van Boxtel MP, Ocké M, Verschuren WM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004;62:275–280.

    Article  CAS  PubMed  Google Scholar 

  14. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003;60:940–946.

    Article  PubMed  Google Scholar 

  15. Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006;63:1545–1550.

    Article  PubMed  Google Scholar 

  16. Sands SA, Reid KJ, Windsor SL, Harris WS. The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes. Lipids. 2005;40:343–347.

    Article  CAS  PubMed  Google Scholar 

  17. Lin PY, Chiu CC, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in dementia. J Clin Psychiatry. 2012;73:1245–1254.

    Article  CAS  PubMed  Google Scholar 

  18. Conklin SM, Gianaros PJ, Brown SM, Yao JK, Hariri AR, Manuck SB, Muldoon MF. Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults. Neurosci Lett. 2007;421:209–212.

    Article  CAS  PubMed  Google Scholar 

  19. Pottala JV, Yaffe K, Robinson JG, Espeland MA, Wallace R, Harris WS. Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes: WHIMS-MRI study. Neurology. 2014;82:435–442.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Raji CA, Erickson KI, Lopez OL, Kuller LH, Gach HM, Thompson PM, Riverol M, Becker JT. Regular fish consumption and age-related brain gray matter loss. Am J Prev Med. 2014;47:444–451.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Samieri C, Maillard P, Crivello F, Proust-Lima C, Peuchant E, Helmer C, Amieva H, Allard M, Dartigues JF, Cunnane SC, Mazoyer BM, Barberger-Gateau P. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology. 2012;79:642–650.

    Article  CAS  PubMed  Google Scholar 

  22. Tan ZS, Harris WS, Beiser AS, Au R, Himali JJ, Debette S, Pikula A, Decarli C, Wolf PA, Vasan RS, Robins SJ, Seshadri S. Red blood cell -3 fatty acid levels and markers of accelerated brain aging. Neurology. 2012;78:658–664.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Titova OE, Sjögren P, Brooks SJ, Kullberg J, Ax E, Kilander L, Riserus U, Cederholm T, Larsson EM, Johansson L, Ahlström H, Lind L, Schiöth HB, Benedict C. Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly. Age (Dordr). 2013;35:1495–1505.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Walhovd KB, Storsve AB, Westlye LT, Drevon CA, Fjell AM. Blood markers of fatty acids and vitamin D, cardiovascular measures, body mass index, and physical activity relate to longitudinal cortical thinning in normal aging. Neurobiol Aging. 35:1055-1064.

  25. 2014;Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A, Flöel A. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014;24:3059–3068.

    Article  PubMed  Google Scholar 

  26. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 200;304:1903-1911.

  27. Arai H, Takano M, Miyakawa K, Ota T, Takahashi T, Asaka H, Kawaguchi T. A quantitative near-infrared spectroscopy study: a decrease in cerebral hemoglobin oxygenation in Alzheimer’s disease and mild cognitive impairment. Brain Cogn. 2006;61:189–194.

    Article  PubMed  Google Scholar 

  28. Hock C, Villringer K, Müller-Spahn F, Hofmann M, Schuh-Hofer S, Heekeren H, Wenzel R, Dirnagl U, Villringer A. Near infrared spectroscopy in the diagnosis of Alzheimer’s disease. Ann N Y Acad Sci. 1996;777:22–29.

    Article  CAS  PubMed  Google Scholar 

  29. Zeller JB, Herrmann MJ, Ehlis AC, Polak T, Fallgatter AJ. Altered parietal brain oxygenation in Alzheimer’s disease as assessed with near-infrared spectroscopy. Am J Geriatr Psychiatry. 2010;18:433–441.

    Article  PubMed  Google Scholar 

  30. Pu S, Nakagome K, Yamada T, Matsumura H, Yokoyama K, Kaneko K, Kurosawa Y. Association between fish consumption and prefrontal function during a cognitive task in male Japanese workers: A multi-channel near-infrared spectroscopy study. PLoS One. 2015;10:e0123972.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Jackson PA, Reay JL, Scholey AB, Kennedy DO. DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near IR spectroscopy pilot study. Br J Nutr. 2012;107:1093–1098.

    Article  CAS  PubMed  Google Scholar 

  32. McNamara RK, Able J, Jandacek R, Rider T, Tso P, Eliassen JC, Alfieri D, Weber W, Jarvis K, DelBello MP, Strakowski SM, Adler CM. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr. 2010;91:1060–1067.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Bauer I, Hughes M, Rowsell R, Cockerell R, Pipingas A, Crewther S, Crewther D. Omega-3 supplementation improves cognition and modifies brain activation in young adults. Hum Psychopharmacol. 2014;29:133–144.

    Article  CAS  PubMed  Google Scholar 

  34. Krikorian R, Zimmerman ME, Fleck DE. Inhibitory control in Obsessive-Compulsive Disorder. Brain Cognit. 2004;54:257–259.

    Article  Google Scholar 

  35. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566–572.

    Article  CAS  PubMed  Google Scholar 

  36. Boake EC. Claparede and the Auditory Verbal Learning Test. J Clin Exp Neuropsychol. 2000;22:286–292.

    Article  CAS  PubMed  Google Scholar 

  37. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1983;17:37–49.

    Article  CAS  Google Scholar 

  38. Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén- Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006;63:1402–1408.

    Article  PubMed  Google Scholar 

  39. Schmithorst VJ, Dardzinski BJ, Holland SK. Simultaneous correction of ghost and geometric distortion artifacts in EPI using a multiecho reference scan. IEEE Trans Med Imaging. 2001;20:535–539.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Lee JH, Garwood M, Menon R, Adriany G, Andersen P, Truwit CL, Ugurbil K. High contrast and fast three-dimensional magnetic resonance imaging at high fields. Magn Reson Med. 1995;34:308–312.

    Article  CAS  PubMed  Google Scholar 

  41. Owen AM, Mc Millan KM, Laird AR, Bullmore E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp. 2005;25:46–59.

    Article  PubMed  Google Scholar 

  42. Yetkin FZ, Rosenberg RN, Weiner MF, Purdy PD, Cullum CM. FMRI of working memory in patients with mild cognitive impairment and probable Alzheimer’s disease. Eur Radiol. 2006;16:193–206.

    Article  PubMed  Google Scholar 

  43. Cox RW. AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Comp. Biomed. Res. 1996;29:162–173.

    Article  CAS  Google Scholar 

  44. Chen G, Adleman NE, Saad ZS, Leibenluft E, Cox RW. Applications of multivariate modeling to neuroimaging group analysis: a comprehensive alternative to univariate general linear model. Neuroimage. 2014;99:571–588.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Janssen CI, Kiliaan AJ. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. Prog Lipid Res. 2014;53:1–17.

    Article  CAS  PubMed  Google Scholar 

  46. Cox RW, Jesmanowicz A. Real-time 3D image registration for functional MRI. Magn. Reson. Med. 1999;42:1014–1018.

    Article  CAS  PubMed  Google Scholar 

  47. Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD, Sadat-Hossieny S. Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem. 60:5736-5742.

  48. Rapoport SI, Ramadan E, Basselin M. Docosahexaenoic acid (DHA) incorporation into the brain from plasma, as an in vivo biomarker of brain DHA metabolism and neurotransmission. Prostaglandins Other Lipid Mediat. 2011;96:109–113.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. McNamara RK, Liu Y, Jandacek R, Rider T, Tso P. The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity. Prostaglandins Leukot Essent Fatty Acids. 2008;78:293–304.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Smesny S, Milleit B, Hipler UC, Milleit C, Schäfer MR, Klier CM, Holub M, Holzer I, Berger GE, Otto M, Nenadic I, Berk M, Mc Gorry PD, Sauer H, Amminger GP. Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis. Mol Psychiatry. 2014;19:317–324.

    Article  CAS  PubMed  Google Scholar 

  51. Gattaz WF, Cairns NJ, Levy R, Förstl H, Braus DF, Maras A. Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci. 1996;246:129–131.

    Article  CAS  PubMed  Google Scholar 

  52. Gattaz WF, Forlenza OV, Talib LL, Barbosa NR, Bottino CM. Platelet phospholipase A(2) activity in Alzheimer’s disease and mild cognitive impairment. J Neural Transm. 2004;111:591–601.

    Article  CAS  PubMed  Google Scholar 

  53. Ross BM, Moszczynska A, Erlich J, Kish SJ. Phospholipid-metabolizing enzymes in Alzheimer’s disease: increased lysophospholipid acyltransferase activity and decreased phospholipase A2 activity. J Neurochem. 1998;70:786–793.

    Article  CAS  PubMed  Google Scholar 

  54. Smesny S, Stein S, Willhardt I, Lasch J, Sauer H. Decreased phospholipase A2 activity in cerebrospinal fluid of patients with dementia. J Neural Transm. 2008;115:1173–1179.

    Article  CAS  PubMed  Google Scholar 

  55. Talbot K, Young RA, Jolly-Tornetta C, Lee VM, Trojanowski JQ, Wolf BA. A frontal variant of Alzheimer’s disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex. Neurochem Int. 2000;37:17–31.

    Article  CAS  PubMed  Google Scholar 

  56. Zamroziewicz, MK, Paul EJ, Rubin RD, Barbey AK. Anterior cingulate cortex mediates the relationship between O3PUFAs and executive functions in APOE e4 carriers. Front Aging Neurosci. 2015;7:87.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Beckmann M, Johansen-Berg H, Rushworth MF. Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization. J Neurosci. 2009;29:1175–1190.

    Article  CAS  PubMed  Google Scholar 

  58. Francis ST, Head K, Morris PG, Macdonald IA. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharmacol. 2006;47:S215–S220.

    Article  CAS  PubMed  Google Scholar 

  59. Krikorian R, Eliassen JC, Boespflug EL, Nash TA, Shidler MD. Improved cognitivecerebral function in older adults with chromium supplementation. Nutr. Neurosci. 2010;13:116–122.

    Article  CAS  PubMed  Google Scholar 

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Boespflug, E.L., McNamara, R.K., Eliassen, J.C. et al. Fish oil supplementation increases event-related posterior cingulate activation in older adults with subjective memory impairment. J Nutr Health Aging 20, 161–169 (2016). https://doi.org/10.1007/s12603-015-0609-6

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  • DOI: https://doi.org/10.1007/s12603-015-0609-6

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