Long-chain omega-3 fatty acids improve brain function and structure in older adults.

Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.

[1]  Chris I. Baker,et al.  Teaching an adult brain new tricks: A critical review of evidence for training-dependent structural plasticity in humans , 2013, NeuroImage.

[2]  Steven R. Brenner,et al.  Penetrance of PD in Glucocerebrosidase Gene Mutation Carriers , 2012, Neurology.

[3]  N. Schupf,et al.  Nutrient intake and plasma β-amyloid , 2012, Neurology.

[4]  R. Agrawal,et al.  ‘Metabolic syndrome’ in the brain: deficiency in omega‐3 fatty acid exacerbates dysfunctions in insulin receptor signalling and cognition , 2012, The Journal of physiology.

[5]  A. Andreadis,et al.  Phosphorylation in the amino terminus of tau prevents inhibition of anterograde axonal transport , 2012, Neurobiology of Aging.

[6]  R. N. Spreng,et al.  Executive functions and neurocognitive aging: dissociable patterns of brain activity , 2012, Neurobiology of Aging.

[7]  Carlijn R Hooijmans,et al.  The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer's pathology in animal models of Alzheimer's disease: a systematic review and meta-analysis. , 2012, Journal of Alzheimer's disease : JAD.

[8]  L. Kuller,et al.  Differential Association of Docosahexaenoic and Eicosapentaenoic Acids With Carotid Intima-Media Thickness , 2011, Stroke.

[9]  K. Langa,et al.  Incidence of dementia and cognitive impairment, not dementia in the united states , 2011, Annals of neurology.

[10]  M. Keshavan,et al.  Reduction in perseverative errors with adjunctive ethyl-eicosapentaenoic acid in patients with schizophrenia: Preliminary study. , 2011, Prostaglandins, leukotrienes, and essential fatty acids.

[11]  A. Turken,et al.  The Neural Architecture of the Language Comprehension Network: Converging Evidence from Lesion and Connectivity Analyses , 2011, Front. Syst. Neurosci..

[12]  E. McAuley,et al.  Exercise training increases size of hippocampus and improves memory , 2011, Proceedings of the National Academy of Sciences.

[13]  A. Alexander,et al.  Diffusion tensor imaging of the brain , 2007, Neurotherapeutics.

[14]  Michael Weiner,et al.  Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. , 2010, JAMA.

[15]  A. Blackwell,et al.  Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline , 2010, Alzheimer's & Dementia.

[16]  H. Vankova Mini Mental State , 2010 .

[17]  H. Eichenbaum,et al.  The Episodic Memory System: Neurocircuitry and Disorders , 2010, Neuropsychopharmacology.

[18]  K. Yaffe,et al.  Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association , 2009, Nature Clinical Practice Neurology.

[19]  J. Ballenger,et al.  Dietary patterns and risk of dementia: The Three-City cohort study , 2009 .

[20]  Shih-Yi Huang,et al.  The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: A preliminary randomized double-blind placebo-controlled study , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[21]  F. Gomez-Pinilla,et al.  Brain foods: the effects of nutrients on brain function , 2008, Nature Reviews Neuroscience.

[22]  A. Veronica Witte,et al.  Lifestyle and Memory in the Elderly , 2008, Neuroepidemiology.

[23]  L. Ricceri,et al.  Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain , 2008, Journal of neuroscience research.

[24]  Timothy Edward John Behrens,et al.  Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. , 2007, Brain : a journal of neurology.

[25]  R. Wurtman,et al.  Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils , 2007, Neuroscience.

[26]  A. Hariri,et al.  Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults , 2007, Neuroscience Letters.

[27]  F Keller,et al.  [Reliability and validity of the Revised Beck Depression Inventory (BDI-II). Results from German samples]. , 2007, Der Nervenarzt.

[28]  W. Harris,et al.  Cardiovascular benefits of omega-3 fatty acids. , 2007, Cardiovascular research.

[29]  W. Sturm,et al.  Neuropsychological assessment , 2007, Journal of Neurology.

[30]  M. Hautzinger,et al.  Reliabilität und Validität des revidierten Beck-Depressionsinventars (BDI-II) , 2007, Der Nervenarzt.

[31]  O. Shido,et al.  Docosahexaenoic acid promotes neurogenesis in vitro and in vivo , 2006, Neuroscience.

[32]  E. Vicaut,et al.  Mannheim Carotid Intima-Media Thickness Consensus (2004–2006) , 2006, Cerebrovascular Diseases.

[33]  Lars-Olof Wahlund,et al.  Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. , 2006, Archives of neurology.

[34]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[35]  J. Hauser,et al.  Illness-specific association of val66met BDNF polymorphism with performance on Wisconsin Card Sorting Test in bipolar mood disorder , 2006, Molecular Psychiatry.

[36]  A. Dale,et al.  Effects of age on volumes of cortex, white matter and subcortical structures , 2005, Neurobiology of Aging.

[37]  J. Morris,et al.  Mild cognitive impairment and preclinical Alzheimer's disease. , 2005, Geriatrics.

[38]  I. Frey,et al.  Freiburger Fragebogen zur körperlichen Aktivität-Entwicklung, Prüfung und Anwendung , 2005, Sozial- und Präventivmedizin.

[39]  A. Meyer-Lindenberg,et al.  The Brain-derived Neurotrophic Factor Val66met Polymorphism and Variation in Human Cortical Morphology , 2022 .

[40]  F. Gomez-Pinilla,et al.  Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. , 2004, Journal of neurotrauma.

[41]  D. Alkon,et al.  Insulin and the insulin receptor in experimental models of learning and memory. , 2004, European journal of pharmacology.

[42]  D Kromhout,et al.  Dietary intake of fatty acids and fish in relation to cognitive performance at middle age , 2004, Neurology.

[43]  Bogdan Draganski,et al.  Neuroplasticity: Changes in grey matter induced by training , 2004, Nature.

[44]  Faith M. Gunning-Dixon,et al.  Differential aging of the human striatum: longitudinal evidence. , 2003, AJNR. American journal of neuroradiology.

[45]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[46]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[47]  M Knapp,et al.  Alzheimer's disease in the UK: comparative evidence on cost of illness and volume of health services research funding , 2001, International journal of geriatric psychiatry.

[48]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[49]  C. Fennema-Notestine,et al.  Effects of age on tissues and regions of the cerebrum and cerebellum , 2001, Neurobiology of Aging.

[50]  R. Henson,et al.  Frontal lobes and human memory: insights from functional neuroimaging. , 2001, Brain : a journal of neurology.

[51]  R. Poldrack,et al.  Microstructure of Temporo-Parietal White Matter as a Basis for Reading Ability Evidence from Diffusion Tensor Magnetic Resonance Imaging , 2000, Neuron.

[52]  J Keul,et al.  [Freiburg Questionnaire of physical activity--development, evaluation and application]. , 1999, Sozial- und Praventivmedizin.

[53]  Carl-Walter Kohlmann,et al.  Untersuchungen mit einer deutschen Version der "Positive and Negative Affect Schedule" (PANAS). , 1996 .

[54]  S. Murphy,et al.  Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). , 1991, Journal of neurochemistry.

[55]  P. C. Murphy,et al.  Cerebral Cortex , 2017, Cerebral Cortex.

[56]  L. Laux,et al.  Das State-Trait-Angstinventar. Theoretische Grundlagen and Handanweisung. , 1981 .

[57]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.