Skip to main content Accessibility help

Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults

  • Cutter A. Lindbergh (a1), Catherine M. Mewborn (a1), Billy R. Hammond (a1), Lisa M. Renzi-Hammond (a1), Joanne M. Curran-Celentano (a2) and L. Stephen Miller (a1) (a3)...


Objectives: It is well known that the carotenoids lutein (L) and zeaxanthin (Z) improve eye health and an accumulating evidence base suggests cognitive benefits as well. The present study investigated underlying neural mechanisms using functional magnetic resonance imaging (fMRI). It was hypothesized that lower L and Z concentrations would be associated with neurobiological inefficiency (i.e., increased activation) during cognitive performance. Methods: Forty-three community-dwelling older adults (mean age=72 years; 58% female; 100% Caucasian) were asked to learn and recall pairs of unrelated words in an fMRI-adapted paradigm. L and Z levels were measured in retina (macular pigment optical density) and serum using validated procedures. Results: Following first-level contrasts of encoding and retrieval trials minus control trials (p<.05, family-wise error corrected, minimum voxel cluster=8), L and Z were found to significantly and negatively relate to blood-oxygen-level-dependent signal in central and parietal operculum cortex, inferior frontal gyrus, supramarginal gyrus, planum polare, frontal and middle temporal gyrus, superior parietal lobule, postcentral gyrus, precentral gyrus, occipital cortex bilaterally, and cerebellar regions. Conclusions: To the authors’ knowledge, the present study represents the first attempt to investigate neural mechanisms underlying the relation of L and Z to cognition using fMRI. The observed results suggest that L and Z promote cognitive functioning in old age by enhancing neural efficiency. (JINS, 2017, 23, 11–22)

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults
      Available formats


Corresponding author

Correspondence and reprint requests to: L. Stephen Miller, Department of Psychology, Psychology Building, University of Georgia, Athens, Georgia 30602. E-mail:


Hide All
Akbaraly, N., Faure, H., Gourlet, V., Favier, A., & Berr, C. (2007). Plasma carotenoid levels and cognitive performance in an elderly population: Results of the EVA study. Journals of Gerontology, Series A, Biological Sciences and Medical Sciences, 62(3), 308316.
Arnal, E., Miranda, M., Barcia, J., Bosch-Morell, F., & Romero, F. (2010). Lutein and docosahexaenoic acid prevent cortex lipid peroxidation in streptozotocin-induced diabetic rat cerebral cortex. Journal of Neuroscience, 166(1), 271278.
Baker, C., Peli, E., Knouf, N., & Kanwisher, N. (2005). Reorganization of visual processing in macular degeneration. Journal of Neuroscience, 25(3), 614618.
Banich, M. (1998). The missing link: The role of interhemispheric interaction in attentional processing. Brain and Cognition, 36(2), 128157.
Beatty, S., Nolan, J., Kavanagh, H., & O’Donovan, O. (2004). Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin. Archives of Biochemistry and Biophysics, 430, 7076.
Bian, Q., Gao, S., Zhou, J., Qin, J., Taylor, A., Johnson, E., & Shang, F. (2012). Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells. Free Radical Biology and Medicine, 53(6), 12981307.
Binawade, Y., & Jagtap, A. (2013). Neuroprotective effect of lutein against 3-nitropropionic acid–induced Huntington’s disease–like symptoms: Possible behavioral, biochemical, and cellular alterations. Journal of Medicinal Food, 16(10), 934943.
Binder, J.R., Desai, R.H., Graves, W.W., & Conant, L.L. (2009). Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cerebral Cortex, 19(12), 27672796.
Bookheimer, S., Renner, B., Ekstrom, A., Li, Z., Henning, S., Brown, J., & Small, G. (2013). Pomegranate juice augments memory and fMRI activity in middle-aged and older adults with mild memory complaints. Evidence-Based Complementary and Alternative Medicine, 2013, 946298.
Bookheimer, S., Strojwas, M., Cohen, M., Saunders, A., Pericak-Vance, M., Mazziotta, J., & & Small, G. (2000). Patterns of brain activation in people at risk for Alzheimer’s disease. New England Journal of Medicine, 343(7), 450456.
Bone, R.A., Landrum, J.T., Dixon, Z., Chen, Y., & Llerena, C.M. (2000). Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Experimental Eye Research, 71(3), 239245.
Bone, R., Landrum, J., & Tarsis, S. (1985). Preliminary identification of the human macular pigment. Vision Research, 25(11), 15311535.
Braskie, M., Small, G., & Bookheimer, S. (2009). Entorhinal cortex structure and functional MRI response during an associative verbal memory task. Human Brain Mapping, 30(12), 39813992.
Burke, J., Curran-Celentano, J., & Wenzel, A. (2005). Diet and serum carotenoid concentrations affect macular pigment optical density in adults 45 years and older. Journal of Nutrition, 135(5), 12081214.
Cabeza, R., Anderson, N., Locantore, J., & McIntosh, A. (2002). Aging gracefully: Compensatory brain activity in high-performing older adults. Neuroimage, 17(3), 13941402.
Cabeza, R., Grady, C., Nyberg, L., McIntosh, A., Tulving, E., Kapur, S., & Craik, F. (1997). Age-related differences in neural activity during memory encoding and retrieval: A positron emission tomography study. Journal of Neuroscience, 17(1), 391400.
Cabeza, R., & Nyberg, L. (2000). Imaging Cognition II: An empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience, 12(1), 147.
Cardinault, N., Gorrand, J., Tyssandier, V., Grolier, P., Rock, E., & Borel, P. (2003). Short-term supplementation with lutein affects biomarkers of lutein status similarly in young and elderly subjects. Experimental Gerontology, 38, 573582.
Clément, F., & Belleville, S. (2009). Test–retest reliability of fMRI verbal episodic memory paradigms in healthy older adults and in persons with mild cognitive impairment. Human Brain Mapping, 30(12), 40334047.
Chew, E., Clemons, T., SanGiovanni, J., Danis, R., Ferris, F., Elman, M., & Fish, G. (2014). Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 Report No. 3. Journal of the American Medical Association Ophthalmology, 132(2), 142149.
Chew, E., Clemons, T., Agrón, E., Launer, L., Grodstein, F., & Bernstein, P. (2015). Effect of omega-3 fatty acids, lutein/zeaxanthin, or other nutrient supplementation on cognitive function: The AREDS2 randomized clinical trial. Journal of the American Medical Association, 314(8), 791801.
Convit, A., de Asis, J., de Leon, M., Tarshish, C., De Santi, S., & Rusinek, H. (2000). Atrophy of the medial occipitotemporal, inferior, and middle temporal gyri in non-demented elderly predict decline to Alzheimer’s disease. Neurobiology of Aging, 21(1), 1926.
Costafreda, S., Fu, C., Lee, L., Everitt, B., Brammer, M., & David, A. (2006). A systematic review and quantitative appraisal of fMRI studies of verbal fluency: Role of the left inferior frontal gyrus. Human Brain Mapping, 27(10), 799810.
Craft, N., Haitema, T., Garnett, K., Fitch, K., & Dorey, C. (2004). Carotenoid, tocopherol, and retinol concentrations in elderly human brain. Journal of Nutrition Health and Aging, 8(3), 156162.
Dickerson, B., Salat, D., Bates, J., Atiya, M., Killiany, R., Greve, D., & Sperling, R.A. (2004). Medial temporal lobe function and structure in mild cognitive impairment. Annals of Neurology, 56(1), 2735.
Dickerson, B., & Sperling, R. (2008). Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer’s disease: Insights from functional MRI studies. Neuropsychologia, 46(6), 16241635.
Eickhoff, S., Jbabdi, S., Caspers, S., Laird, A., Fox, P., Zilles, K., && Behrens, T. (2010). Anatomical and functional connectivity of cytoarchitectonic areas within the human parietal operculum. Journal of Neuroscience, 30(18), 64096421.
Engelhart, M.J., Geerlings, M.I., Meijer, J., Kiliaan, A., Ruitenberg, A., van Swieten, J.C., & Breteler, M.M. (2004). Inflammatory proteins in plasma and the risk of dementia: The Rotterdam Study. Archives of Neurology, 61(5), 668672.
Feart, C., Letenneur, L., Helmer, C., Samieri, C., Schalch, W., Etheve, S., & Barberger-Gateau, P. (2016). Plasma carotenoids are inversely associated with dementia risk in an elderly French cohort. Journals of Gerontology, Series A, Biological Sciences and Medical Sciences, 71(5), 683688.
Feeney, J., Finucane, C., Savva, G.M., Cronin, H., Beatty, S., Nolan, J.M., && Kenny, R.A. (2013). Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults. Neurobiology of Aging, 34(11), 24492456.
Fera, F., Weickert, T.W., Goldberg, T.E., Tessitore, A., Hariri, A., Das, S., & Mattay, V. (2005). Neural mechanisms underlying probabilistic category learning in normal aging. Journal of Neuroscience, 25(49), 1134011348.
Finkel, T., & Holbrook, N. (2000). Oxidants, oxidative stress and the biology of ageing. Nature, 408(6809), 239247.
Friederici, A., Meyer, M., & von Cramon, D. (2000). Auditory language comprehension: An event-related fMRI study on the processing of syntactic and lexical information. Brain and Language, 74(2), 289300.
Gutchess, A., Welsh, R., Hedden, T., Bangert, A., Minear, M., Liu, L., && Park, D. (2005). Aging and the neural correlates of successful picture encoding: Frontal activations compensate for decreased medial-temporal activity. Journal of Cognitive Neuroscience, 17(1), 8496.
Hammond, B.R., Johnson, E.J., Russell, R.M., Krinsky, N., Yeum, K., Edwards, R., & & Snodderly, D. (1997). Dietary modification of human macular pigment density. Investigative Opthalmology & Visual Science, 38(9), 17951801.
Hammond, B., Wooten, B., & Smollon, B. (2005). Assessment of the validity of in vivo methods of measuring human macular pigment optical density. Optometry & Vision Science, 82(5), 387404.
Handelman, G.J., Shen, B., & Krinksy, N.I. (1992). High resolution analysis of carotenoids in human plasma by high-performance liquid chromatography. Methods in Enzymology, 213, 336346.
Hillary, F.G., Genova, H.M., Chiaravalloti, N.D., Rypma, B., & DeLuca, J. (2006). Prefrontal modulation of working memory performance in brain injury and disease. Human Brain Mapping, 27(11), 837847.
Huang, C.-M., Polk, T., Goh, J., & Park, D. (2012). Both left and right posterior parietal activations contribute to compensatory processes in normal aging. Neuropsychologia, 50(1), 5566.
Johnson, E.J. (2012). A possible role for lutein and zeaxanthin in cognitive function in the elderly. American Journal of Clinical Nutrition, 96(5), 11611165.
Johnson, E. (2014). Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutrition Reviews, 72(9), 605612.
Johnson, E., Maras, J.E., Rasmussen, H.M., & Tucker, K.L. (2010). Intake of lutein and zeaxanthin differ with age, sex, and ethnicity. Journal of the American Dietetic Association, 110(9), 13571362.
Johnson, E., McDonald, K., Caldarella, S., Chung, H., Troen, A., & Snodderly, D. (2008). Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutritional Neuroscience, 11(2), 7583.
Johnson, E.J., Vishwanathan, R., Johnson, M.A., Hausman, D.B., Davey, A., Scott, T.M., & Poon, L.W. (2013). Relationship between serum and brain carotenoids, α-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. Journal of Aging Research, 2013, 951786.
Kang, J., Ascherio, A., & Grodstein, F. (2005). Fruit and vegetable consumption and cognitive decline in aging women. Annals of Neurology, 57(5), 713720.
Krinsky, N. (2002). Possible biologic mechanisms for a protective role of xanthophylls. The Journal of Nutrition, 132(3), 540542.
Krinsky, N., Mayne, S., & Sies, H. (2004). Carotenoids in health and disease. Florida: CRC Press.
Kuhad, A., Sethi, R., & Chopra, K. (2008). Lycopene attenuates diabetes-associated cognitive decline in rats. Life Sciences, 83(3-4), 128134.
Lazar, N. (2008). The statistical analysis of functional MRI data. New York: Springer.
Li, S., Fung, F., Fu, Z., Wong, D., Chan, H., & Lo, A. (2012). Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: In vivo and in vitro studies. Investigative Ophthalmology and Visual Science, 53(10), 59765984.
Lorenzi, M.M., Beltramello, A., Mercuri, N.B., Canu, E., Zoccatelli, G., Pizzini, F.B., & Frisoni, G.B. (2011). Effect of memantine on resting state default mode network activity in Alzheimer’s disease. Drugs and Aging, 28(3), 205217.
Min, J., & Min, K. (2014). Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer’s disease mortality in older adults. Dementia and Geriatric Cognitive Disorders, 37(3-4), 246256.
Molholm, S., Sehatpour, P., Mehta, A.D., Shpaner, M., Gomez-Ramirez, M., Ortigue, S., & Foxe, J.J. (2006). Audio-visual multisensory integration in superior parietal lobule revealed by human intracranial recordings. Journal of Neurophysiology, 96(2), 721729.
Morris, M.C., Evans, D., Tangney, C., Bienias, J., & Wilson, R.S. (2006). Associations of vegetable and fruit consumption with age-related cognitive change. Neurology, 67(8), 13701376.
Muriach, M., Bosch-Morell, F., Alexander, G., Blomhoff, R., Barcia, J., Arnal, E., & Miranda, M. (2006). Lutein effect on retina and hippocampus of diabetic mice. Free Radical Biology and Medicine, 41(6), 979984.
Nakashima, Y., Ohsawa, I., Konishi, F., Hasegawa, T., Kumamoto, S., Suzuki, Y., & & Ohta, S. (2009). Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice. Neuroscience Letters, 464(3), 193198.
Nolan, J.M., Loskutova, E., Howard, A.N., Moran, R., Mulcahy, R., Stack, J., & Beatty, S. (2014). Macular pigment, visual function, and macular disease among subjects with Alzheimer’s disease: An exploratory study. Journal of Alzheimer’s Disease, 42(4), 11911202.
Nolan, J.M., Stack, J., Mellerio, J., Godhinio, M., O’Donovan, O., Neelam, K., && Beatty, S. (2006). Monthly consistency of macular pigment optical density and serum concentrations of lutein and zeaxanthin. Current Eye Research, 31(2), 199213.
Olmedilla-Alonso, B., Beltrán-de-Miguel, B., Estévez-Santiago, R., & Cuadrado-Vives, C. (2014). Markers of lutein and zeaxanthin status in two age groups of men and women: Dietary intake, serum concentrations, lipid profile and macular pigment optical density. Nutrition Journal, 13(1), 142160.
Pappolla, M.A., Smith, M.A., Bryant-Thomas, T., Bazan, N., Petanceska, S., Perry, G., & Refolo, L.M. (2002). Cholesterol, oxidative stress, and Alzheimer’s disease: Expanding the horizons of pathogenesis. Free Radical Biology and Medicine, 33(2), 173181.
Park, D.C., & Reuter-Lorenz, P. (2009). The adaptive brain: Aging and neurocognitive scaffolding. Annual Review of Psychology, 60, 173196.
Petersen, S.E., Van Mier, H., Fiez, J.A., & Raichle, M.E. (1998). The effects of practice on the functional anatomy of task performance. Proceedings of the National Academy of Sciences of the United States of America, 95(3), 853860.
Qin, J.Y., Yeum, K.J., Johnson, E.J., Krinsky, N.I., Russell, R.M., & Tang, G. (2008). Determination of 9-cis β-carotene and ζ-carotene in biological samples. Journal of Nutritional Biochemistry, 19(9), 612618.
Rajah, M.N., Languay, R., & Grady, C.L. (2011). Age-related changes in right middle frontal gyrus volume correlate with altered episodic retrieval activity. Journal of Neuroscience, 31(49), 1794117954.
Renzi, L., & Hammond, B.R. (2010). The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision. Ophthalmic and Physiological Optics, 30(4), 351357.
Renzi, L.M., Hammond, B.R., Dengler, M., & Roberts, R. (2012). The relation between serum lipids and lutein and zeaxanthin in the serum and retina: Results from cross-sectional, case-control and case study designs. Lipids in Health and Disease, 11(1), 110.
Renzi, L.M., Dengler, M.J., Puente, A., Miller, L.S., & Hammond, B.R. Jr. (2014). Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults. Neurobiology of Aging, 35(7), 16951699.
Rinaldi, P., Polidori, M., Metastasio, A., Mariani, E., Mattioli, P., Cherubini, A., & Mecocci, P. (2003). Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiology of Aging, 24(7), 915919.
Rorden, C. (2007). DCM2NII (Computer software). Retrieved from
Sasaki, M., Ozawa, Y., Kurihara, T., Noda, K., Imamura, Y., Kobayashi, S., & Tsubota, K. (2009). Neuroprotective effect of an antioxidant, lutein, during retinal inflammation. Investigative Opthalmology and Visual Science, 50(3), 1433.
Saykin, A.J., Flashman, L.A., Frutiger, S.A., Johnson, S.C., Mamourian, A.C., Moritz, C.H., & Weaver, J.B. (1999). Neuroanatomic substrates of semantic memory impairment in Alzheimer’s disease: Patterns of functional MRI activation. Journal of the International Neuropsychological Society, 5(5), 377392.
Scanlon, G., Connell, P., Ratzlaff, M., Foerg, B., McCartney, D., Murphy, A., & Loughman, J. (2015). Macular pigment optical density is lower in type 2 diabetes, compared with type 1 diabetes and normal controls. Retina, 35(9), 18081816.
Stahl, W., & Sies, H. (2001). Effects of carotenoids and retinoids on gap junctional communication. Biofactors, 15(2‐4), 9598.
Stringham, J.M., Hammond, B.R., Nolan, J.M., Wooten, B.R., Mammen, A., Smollon, W., && Snodderly, D.M. (2008). The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration. Experimental Eye Research, 87(5), 445453.
Teunissen, C.E., Van Boxtel, M.P.J., Bosma, H., Bosmans, E., Delanghe, J., De Bruijn, C., & De Vente, J. (2003). Inflammation markers in relation to cognition in a healthy aging population. Journal of Neuroimmunology, 134(1), 142150.
Trachtenberg, A.J., Filippini, N., Ebmeier, K.P., Smith, S.M., Karpe, F., & Mackay, C.E. (2012). The effects of APOE on the functional architecture of the resting brain. Neuroimage, 59(1), 565572.
Vishwanathan, R., Iannaccone, A., Scott, T.M., Kritchevsky, S.B., Jennings, B.J., Carboni, G., & Johnson, E.J. (2014). Macular pigment optical density is related to cognitive function in older people. Age and Ageing, 43(2), 271275.
Vishwanathan, R., Kuchan, M., Sen, S., & Johnson, E. (2014). Lutein and preterm infants with decreased concentrations of brain carotenoids. Journal of Pediatric Gastroenterology and Nutrition, 59(5), 659665.
Vishwanathan, R., Neuringer, M., Snodderly, D.M., Schalch, W., & Johnson, E.J. (2013). Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutritional Neuroscience, 16(1), 2129.
Wechsler, D. (2001). Wechsler Test of Adult Reading: WTAR. San Antonio, TX: Psychological Corporation.
Wechsler, D. (2009). The Wechsler Memory Scale-Fourth Edition (WMS-IV). San Antonio, TX: Pearson Assessments.
Wang, W., Shinto, L., Connor, W.E., & Quinn, J.F. (2008). Nutritional biomarkers in Alzheimer’s disease: The association between carotenoids, n-3 fatty acids, and dementia severity. Journal of Alzheimer’s Disease, 13(1), 3138.
Witte, A.V., Kerti, L., Hermannstädter, H.M., Fiebach, J.B., Schreiber, S.J., Schuchardt, J.P., & Flöel, A. (2014). Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cerebral Cortex, 24(11), 30593068.
Xie, C., Bai, F., Yu, H., Shi, Y., Yuan, Y., Chen, G., & Li, S. (2012). Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment. Neuroimage, 63(1), 320327.
Yesavage, J.A., Brink, T.L., Rose, T.L., Lum, O., Huang, V., Adey, M., && Leirer, V.O. (1983). Development and validation of a geriatric depression screening scale: A preliminary report. Journal of Psychiatric Research, 17(1), 3749.


Related content

Powered by UNSILO

Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults

  • Cutter A. Lindbergh (a1), Catherine M. Mewborn (a1), Billy R. Hammond (a1), Lisa M. Renzi-Hammond (a1), Joanne M. Curran-Celentano (a2) and L. Stephen Miller (a1) (a3)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.