Advertisement

GeroScience

, Volume 39, Issue 5–6, pp 571–584 | Cite as

Chronic curcumin treatment improves spatial working memory but not recognition memory in middle-aged rhesus monkeys

  • Tara L. Moore
  • Bethany Bowley
  • Penny Shultz
  • Samantha Calderazzo
  • Eli Shobin
  • Ronald J. Killiany
  • Douglas L. Rosene
  • Mark B. Moss
Original Article

Abstract

Studies of both humans and non-human primates have demonstrated that aging is typically characterized by a decline in cognition that can occur as early as the fifth decade of life. Age-related changes in working memory are particularly evident and mediated, in part, by the prefrontal cortex, an area known to evidence age-related changes in myelin that is attributed to inflammation. In recent years, several nutraceuticals, including curcumin, by virtue of their anti-inflammatory and antioxidant effects, have received considerable attention as potential treatments for age-related cognitive decline and inflammation. Accordingly, we assessed for the first time in a non-human primate model of normal aging the efficacy of dietary intervention using the natural phenol curcumin to ameliorate the effects of aging on spatial working and recognition memory. Results revealed that monkeys receiving daily administration of curcumin over 14–18 months demonstrated a greater improvement in performance on repeated administration of a task of spatial working memory compared to monkeys that received a control substance.

Keywords

Curcumin Cognition Aging Rhesus monkey Memory 

Notes

Acknowledgments

The authors would like to thank Verdure Sciences for their generous donation of the Longvida Curcumin and control vehicle used in this study. We would also like to thank Reese Edwards and Karen Slater for their technical assistance with this study.

Funding

This study was supported by the National Institutes of Health—National Institute of Aging R01-AG043478 and R01-AG043640.

References

  1. Albert M (1984) Age related changes in cognitive function. In: M. A. M. Albert, MB (Ed.), Geriatric Neuropsychology. Guilford Press, New YorkGoogle Scholar
  2. Arnsten AF, Goldman-Rakic PS (1990) Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys. Neurobiol Aging 11(6):583–590CrossRefPubMedGoogle Scholar
  3. Arnsten AF, Jentsch JD (1997) The alpha-1 adrenergic agonist, cirazoline, impairs spatial working memory performance in aged monkeys. Pharmacol Biochem Behav 58(1):55–59CrossRefPubMedGoogle Scholar
  4. Arshad L, Haque MA, Abbas Bukhari SN, Jantan I (2017) An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents. Future Med Chem 9(6):605–626.  https://doi.org/10.4155/fmc-2016-0223 CrossRefPubMedGoogle Scholar
  5. Arshad M, Stanley JA, Raz N (2016) Adult age differences in subcortical myelin content are consistent with protracted myelination and unrelated to diffusion tensor imaging indices. NeuroImage 143:26–39.  https://doi.org/10.1016/j.neuroimage.2016.08.047 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bachevalier J (1993) Behavioral changes in aged rhesus monkeys. Neurobiol Aging 14(6):619–621CrossRefPubMedGoogle Scholar
  7. Bachevalier J, Landis LS, Walker LC, Brickson M, Mishkin M, Price DL, Cork LC (1991) Aged monkeys exhibit behavioral deficits indicative of widespread cerebral dysfunction. Neurobiol Aging 12(2):99–111CrossRefPubMedGoogle Scholar
  8. Begum, A. N., Jones, M. R., Lim, G. P., Morihara, T., Kim, P., Heath, D. D.,. .. Frautschy, S. A. (2008). Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther, 326(1), 196–208.  https://doi.org/10.1124/jpet.108.137455 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Borella E, Meneghetti C, Ronconi L, De Beni R (2014) Spatial abilities across the adult life span. Dev Psychol 50(2):384–392.  https://doi.org/10.1037/a0033818 CrossRefPubMedGoogle Scholar
  10. Bowley MP, Cabral H, Rosene DL, Peters A (2010) Age changes in myelinated nerve fibers of the cingulate bundle and corpus callosum in the rhesus monkey. J Comp Neurol 518(15):3046–3064.  https://doi.org/10.1002/cne.22379 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brown LA (2016) Spatial-sequential working memory in younger and older adults: age predicts backward recall performance within both age groups. Front Psychol 7:1514.  https://doi.org/10.3389/fpsyg.2016.01514 PubMedPubMedCentralGoogle Scholar
  12. Cahn-Weiner DA, Malloy PF, Boyle PA, Marran M, Salloway S (2000) Prediction of functional status from neuropsychological tests in community-dwelling elderly individuals. Clin Neuropsychol 14(2):187–195.  https://doi.org/10.1076/1385-4046(200005)14:2;1-Z;FT187 CrossRefPubMedGoogle Scholar
  13. Chodosh J, Reuben DB, Albert MS, Seeman TE (2002) Predicting cognitive impairment in high-functioning community-dwelling older persons: MacArthur studies of successful aging. J Am Geriatr Soc 50(6):1051–1060CrossRefPubMedGoogle Scholar
  14. Cole GM, Teter B, Frautschy SA (2007) Neuroprotective effects of curcumin. Adv Exp Med Biol 595:197–212.  https://doi.org/10.1007/978-0-387-46401-5_8 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Cornejo F, von Bernhardi R (2016) Age-dependent changes in the activation and regulation of microglia. Adv Exp Med Biol 949:205–226.  https://doi.org/10.1007/978-3-319-40764-7_10 CrossRefPubMedGoogle Scholar
  16. Cox KH, Pipingas A, Scholey AB (2015) Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol 29(5):642–651.  https://doi.org/10.1177/0269881114552744 CrossRefPubMedGoogle Scholar
  17. Darusman HS, Call J, Sajuthi D, Schapiro SJ, Gjedde A, Kalliokoski O, Hau J (2014) Delayed response task performance as a function of age in cynomolgus monkeys (Macaca Fascicularis). Primates 55(2):259–267.  https://doi.org/10.1007/s10329-013-0397-8 CrossRefPubMedGoogle Scholar
  18. Di Benedetto S, Müller L, Wenger E, Düzel S, Pawelec G (2017) Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions. Neurosci Biobehav Rev 75:114–128.  https://doi.org/10.1016/j.neubiorev.2017.01.044 CrossRefPubMedGoogle Scholar
  19. Drag LL, Bieliauskas LA (2010) Contemporary review 2009: cognitive aging. J Geriatr Psychiatry Neurol 23(2):75–93.  https://doi.org/10.1177/0891988709358590 CrossRefPubMedGoogle Scholar
  20. Frick KM, Baxter MG, Markowska AL, Olton DS, Price DL (1995) Age-related spatial reference and working memory deficits assessed in the water maze. Neurobiol Aging 16(2):149–160CrossRefPubMedGoogle Scholar
  21. Fristoe NM, Salthouse TA, Woodard JL (1997) Examination of age-related deficits on the Wisconsin card sorting test. Neuropsychology 11(3):428–436CrossRefPubMedGoogle Scholar
  22. Funahashi S (2017) Working memory in the prefrontal cortex. Brain Sci 7(5).  https://doi.org/10.3390/brainsci7050049
  23. Grabowska W, Sikora E, Bielak-Zmijewska A (2017) Sirtuins, a promising target in slowing down the ageing process. Biogerontology.  https://doi.org/10.1007/s10522-017-9685-9
  24. Guttmann CR, Jolesz FA, Kikinis R, Killiany RJ, Moss MB, Sandor T, Albert MS (1998) White matter changes with normal aging. Neurology 50(4):972–978CrossRefPubMedGoogle Scholar
  25. Hara Y, Rapp PR, Morrison JH (2012) Neuronal and morphological bases of cognitive decline in aged rhesus monkeys. Age (Dordr) 34(5):1051–1073.  https://doi.org/10.1007/s11357-011-9278-5 CrossRefGoogle Scholar
  26. Herndon JG, Moss MB, Rosene DL, Killiany RJ (1997) Patterns of cognitive decline in aged rhesus monkeys. Behav Brain Res 87(1):25–34CrossRefPubMedGoogle Scholar
  27. Hilsabeck, R. C., Anstead, G. M., Webb, A. L., Hoyumpa, A., Ingmundson, P., Holliday, S.,. .. Stern, S. L. (2010). Cognitive efficiency is associated with endogenous cytokine levels in patients with chronic hepatitis C. J Neuroimmunol, 221(1–2), 53–61.  https://doi.org/10.1016/j.jneuroim.2010.01.017 CrossRefPubMedGoogle Scholar
  28. Hussain Z, Thu HE, Amjad MW, Hussain F, Ahmed TA, Khan S (2017) Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: a review of new trends and future perspectives. Mater Sci Eng C Mater Biol Appl 77:1316–1326.  https://doi.org/10.1016/j.msec.2017.03.226 CrossRefPubMedGoogle Scholar
  29. Jin CY, Lee JD, Park C, Choi YH, Kim GY (2007) Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. Acta Pharmacol Sin 28(10):1645–1651.  https://doi.org/10.1111/j.1745-7254.2007.00651.x CrossRefPubMedGoogle Scholar
  30. Johnson, S. A., Sacks, P. K., Turner, S. M., Gaynor, L. S., Ormerod, B. K., Maurer, A. P.,. .. Burke, S. N. (2016). Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory. Learn Mem, 23(7), 339–348.  https://doi.org/10.1101/lm.042069.116 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Killiany RJ, Moss MB, Rosene DL, Herndon J (2000) Recognition memory function in early senescent rhesus monkeys. Psychobiology 28(1):45–56.  https://doi.org/10.3758/bf03330628 Google Scholar
  32. Kure C, Timmer J, Stough C (2017) The Immunomodulatory effects of plant extracts and plant secondary metabolites on chronic Neuroinflammation and cognitive aging: a mechanistic and empirical review. Front Pharmacol 8:117.  https://doi.org/10.3389/fphar.2017.00117 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kwon D, Maillet D, Pasvanis S, Ankudowich E, Grady CL, Rajah MN (2016) Context memory decline in middle aged adults is related to changes in prefrontal cortex function. Cereb Cortex 26(6):2440–2460.  https://doi.org/10.1093/cercor/bhv068 CrossRefPubMedGoogle Scholar
  34. Lai ZC, Moss MB, Killiany RJ, Rosene DL, Herndon JG (1995) Executive system dysfunction in the aged monkey: spatial and object reversal learning. Neurobiol Aging 16(6):947–954CrossRefPubMedGoogle Scholar
  35. Lee, H. S., Jung, K. K., Cho, J. Y., Rhee, M. H., Hong, S., Kwon, M.,. .. Kang, S. Y. (2007). Neuroprotective effect of curcumin is mainly mediated by blockade of microglial cell activation. Pharmazie, 62(12), 937–942PubMedGoogle Scholar
  36. León I, Tascón L, Cimadevilla JM (2016) Age and gender-related differences in a spatial memory task in humans. Behav Brain Res 306:8–12.  https://doi.org/10.1016/j.bbr.2016.03.008 CrossRefPubMedGoogle Scholar
  37. Light LL (1991) Memory and aging: four hypotheses in search of data. Annu Rev Psychol 42:333–376.  https://doi.org/10.1146/annurev.ps.42.020191.002001 CrossRefPubMedGoogle Scholar
  38. Lim A, Krajina K, Marsland AL (2013) Peripheral inflammation and cognitive aging. Mod Trends Pharmacopsychiatry 28:175–187.  https://doi.org/10.1159/000346362 CrossRefPubMedGoogle Scholar
  39. Ma F, Liu F, Ding L, You M, Yue H, Zhou Y, Hou Y (2017) Anti-inflammatory effects of curcumin are associated with down regulating microRNA-155 in LPS-treated macrophages and mice. Pharm Biol 55(1):1263–1273.  https://doi.org/10.1080/13880209.2017.1297838 CrossRefPubMedGoogle Scholar
  40. Makris, N., Papadimitriou, G. M., van der Kouwe, A., Kennedy, D. N., Hodge, S. M., Dale, A. M.,. .. Rosene, D. L. (2007). Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI study. Neurobiol Aging, 28(10), 1556–1567.  https://doi.org/10.1016/j.neurobiolaging.2006.07.005 CrossRefPubMedGoogle Scholar
  41. McEwen BS, Morrison JH (2013) The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course. Neuron 79(1):16–29.  https://doi.org/10.1016/j.neuron.2013.06.028 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Moore TL, Killiany RJ, Herndon JG, Rosene DL, Moss MB (2003) Impairment in abstraction and set shifting in aged rhesus monkeys. Neurobiol Aging 24(1):125–134CrossRefPubMedGoogle Scholar
  43. Moore TL, Killiany RJ, Herndon JG, Rosene DL, Moss MB (2006) Executive system dysfunction occurs as early as middle-age in the rhesus monkey. Neurobiol Aging 27(10):1484–1493.  https://doi.org/10.1016/j.neurobiolaging.2005.08.004 CrossRefPubMedGoogle Scholar
  44. Moore TL, Schettler SP, Killiany RJ, Herndon JG, Luebke JI, Moss MB, Rosene DL (2005) Cognitive impairment in aged rhesus monkeys associated with monoamine receptors in the prefrontal cortex. Behav Brain Res 160(2):208–221.  https://doi.org/10.1016/j.bbr.2004.12.003 CrossRefPubMedGoogle Scholar
  45. Moss M, Moore T, Schettler S, Killiany R, Rosene D (2007) Successful vs. unsuccessful aging in the rhesus monkey. In: Riddle DR (ed) Brain aging: models, methods and mechanisms. CRC Press, Boca Raton, pp 21–38Google Scholar
  46. Moss MB, Killiany RJ, Lai ZC, Rosene DL, Herndon JG (1997) Recognition memory span in rhesus monkeys of advanced age. Neurobiol Aging 18(1):13–19CrossRefPubMedGoogle Scholar
  47. Moss MB, Rosene DL, Peters A (1988) Effects of aging on visual recognition memory in the rhesus monkey. Neurobiol Aging 9(5–6):495–502CrossRefPubMedGoogle Scholar
  48. Nahar PP, Slitt AL, Seeram NP (2015) Anti-inflammatory effects of novel standardized solid lipid Curcumin formulations. J Med Food 18(7):786–792.  https://doi.org/10.1089/jmf.2014.0053 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Nam, S. M., Choi, J. H., Yoo, D. Y., Kim, W., Jung, H. Y., Kim, J. W.,. .. Hwang, I. K. (2014). Effects of curcumin (Curcuma Longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling. J Med Food, 17(6), 641–649. doi: https://doi.org/10.1089/jmf.2013.2965 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH (2006) Curry consumption and cognitive function in the elderly. Am J Epidemiol 164(9):898–906.  https://doi.org/10.1093/aje/kwj267 CrossRefPubMedGoogle Scholar
  51. Ownby RL (2010) Neuroinflammation and cognitive aging. Curr Psychiatry Rep 12(1):39–45.  https://doi.org/10.1007/s11920-009-0082-1 CrossRefPubMedGoogle Scholar
  52. Parada E, Buendia I, Navarro E, Avendaño C, Egea J, López MG (2015) Microglial HO-1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects. Mol Nutr Food Res 59(9):1690–1700.  https://doi.org/10.1002/mnfr.201500279 CrossRefPubMedGoogle Scholar
  53. Peters A, Leahu D, Moss MB, McNally KJ (1994) The effects of aging on area 46 of the frontal cortex of the rhesus monkey. Cereb Cortex 4(6):621–635CrossRefPubMedGoogle Scholar
  54. Peters A, Moss MB, Sethares C (2000) Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J Comp Neurol 419(3):364–376CrossRefPubMedGoogle Scholar
  55. Peters A, Sethares C (2002) Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey. J Comp Neurol 442(3):277–291CrossRefPubMedGoogle Scholar
  56. Peters A, Sethares C, Killiany RJ (2001) Effects of age on the thickness of myelin sheaths in monkey primary visual cortex. J Comp Neurol 435(2):241–248CrossRefPubMedGoogle Scholar
  57. Rabbitt P, Lowe C (2000) Patterns of cognitive ageing. Psychol Res 63(3–4):308–316CrossRefPubMedGoogle Scholar
  58. Rainey-Smith SR, Brown BM, Sohrabi HR, Shah T, Goozee KG, Gupta VB, Martins RN (2016) Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr 115(12):2106–2113.  https://doi.org/10.1017/S0007114516001203 CrossRefPubMedGoogle Scholar
  59. Rapp PR, Amaral DG (1989) Evidence for task-dependent memory dysfunction in the aged monkey. J Neurosci 9(10):3568–3576PubMedGoogle Scholar
  60. Rapp PR, Amaral DG (1991) Recognition memory deficits in a subpopulation of aged monkeys resemble the effects of medial temporal lobe damage. Neurobiol Aging 12(5):481–486CrossRefPubMedGoogle Scholar
  61. Raz, N., Gunning, F. M., Head, D., Dupuis, J. H., McQuain, J., Briggs, S. D.,. .. Acker, J. D. (1997). Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. Cereb Cortex, 7(3), 268–282CrossRefPubMedGoogle Scholar
  62. Robillard KN, Lee KM, Chiu KB, MacLean AG (2016) Glial cell morphological and density changes through the lifespan of rhesus macaques. Brain Behav Immun 55:60–69.  https://doi.org/10.1016/j.bbi.2016.01.006 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Ryu EK, Choe YS, Lee KH, Choi Y, Kim BT (2006) Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem 49(20):6111–6119.  https://doi.org/10.1021/jm0607193 CrossRefPubMedGoogle Scholar
  64. Safaiyan, S., Kannaiyan, N., Snaidero, N., Brioschi, S., Biber, K., Yona, S.,. .. Simons, M. (2016). Age-related myelin degradation burdens the clearance function of microglia during aging. Nat Neurosci, 19(8), 995–998.  https://doi.org/10.1038/nn.4325 CrossRefPubMedGoogle Scholar
  65. Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T (2008) Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing Res Rev 7(2):83–105.  https://doi.org/10.1016/j.arr.2007.09.002 CrossRefPubMedGoogle Scholar
  66. Salvioli S, Sikora E, Cooper EL, Franceschi C (2007) Curcumin in cell death processes: a challenge for CAM of age-related pathologies. Evid Based Complement Alternat Med 4(2):181–190.  https://doi.org/10.1093/ecam/nem043 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Shamy, J. L., Habeck, C., Hof, P. R., Amaral, D. G., Fong, S. G., Buonocore, M. H.,. .. Rapp, P. R. (2011). Volumetric correlates of spatiotemporal working and recognition memory impairment in aged rhesus monkeys. Cereb Cortex, 21(7), 1559–1573.  https://doi.org/10.1093/cercor/bhq210 CrossRefPubMedGoogle Scholar
  68. Sikora E, Bielak-Zmijewska A, Mosieniak G, Piwocka K (2010a) The promise of slow down ageing may come from curcumin. Curr Pharm Des 16(7):884–892CrossRefPubMedGoogle Scholar
  69. Sikora E, Scapagnini G, Barbagallo M (2010b) Curcumin, inflammation, ageing and age-related diseases. Immun Ageing 7(1):1.  https://doi.org/10.1186/1742-4933-7-1 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Simen AA, Bordner KA, Martin MP, Moy LA, Barry LC (2011) Cognitive dysfunction with aging and the role of inflammation. Ther Adv Chronic Dis 2(3):175–195.  https://doi.org/10.1177/2040622311399145 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Souchay C, Isingrini M, Espagnet L (2000) Aging, episodic memory feeling-of-knowing, and frontal functioning. Neuropsychology 14(2):299–309CrossRefPubMedGoogle Scholar
  72. Sridharan, A., Willette, A. A., Bendlin, B. B., Alexander, A. L., Coe, C. L., Voytko, M. L.,. .. Johnson, S. C. (2012). Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys. Front Aging Neurosci, 4, 31.  https://doi.org/10.3389/fnagi.2012.00031 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Tegenge MA, Rajbhandari L, Shrestha S, Mithal A, Hosmane S, Venkatesan A (2014) Curcumin protects axons from degeneration in the setting of local neuroinflammation. Exp Neurol 253:102–110.  https://doi.org/10.1016/j.expneurol.2013.12.016 CrossRefPubMedGoogle Scholar
  74. Toepper, M., Markowitsch, H. J., Gebhardt, H., Beblo, T., Bauer, E., Woermann, F. G.,. .. Sammer, G. (2014). The impact of age on prefrontal cortex integrity during spatial working memory retrieval. Neuropsychologia, 59, 157–168.  https://doi.org/10.1016/j.neuropsychologia.2014.04.020 CrossRefPubMedGoogle Scholar
  75. Voytko ML (1999) Impairments in acquisition and reversals of two-choice discriminations by aged rhesus monkeys. Neurobiol Aging 20(6):617–627CrossRefPubMedGoogle Scholar
  76. Wirt RA, Hyman JM (2017) Integrating spatial working memory and remote memory: interactions between the medial prefrontal cortex and hippocampus. Brain Sci 7(4).  https://doi.org/10.3390/brainsci7040043
  77. Wisco JJ, Killiany RJ, Guttmann CR, Warfield SK, Moss MB, Rosene DL (2008) An MRI study of age-related white and gray matter volume changes in the rhesus monkey. Neurobiol Aging 29(10):1563–1575.  https://doi.org/10.1016/j.neurobiolaging.2007.03.022 CrossRefPubMedGoogle Scholar
  78. Xie F, Zhang JC, Fu H, Chen J (2013) Age-related decline of myelin proteins is highly correlated with activation of astrocytes and microglia in the rat CNS. Int J Mol Med 32(5):1021–1028.  https://doi.org/10.3892/ijmm.2013.1486 CrossRefPubMedGoogle Scholar
  79. Yang Z, Zhao T, Zou Y, Zhang JH, Feng H (2014) Curcumin inhibits microglia inflammation and confers neuroprotection in intracerebral hemorrhage. Immunol Lett 160(1):89–95.  https://doi.org/10.1016/j.imlet.2014.03.005 CrossRefPubMedGoogle Scholar
  80. Zeamer A, Clark K, Bouquio C, Decamp E, Schneider JS (2012) Impaired spatial working memory learning and performance in normal aged rhesus monkeys. Behav Brain Res 232(1):287–293.  https://doi.org/10.1016/j.bbr.2012.04.023 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Zeamer A, Decamp E, Clark K, Schneider JS (2011) Attention, executive functioning and memory in normal aged rhesus monkeys. Behav Brain Res 219(1):23–30.  https://doi.org/10.1016/j.bbr.2010.12.021 CrossRefPubMedGoogle Scholar

Copyright information

© American Aging Association 2017

Authors and Affiliations

  1. 1.Department of Anatomy & NeurobiologyBoston University School of MedicineBostonUSA
  2. 2.Department of NeurologyBoston University School of MedicineBostonUSA
  3. 3.Graduate Program in NeuroscienceBoston University School of MedicineBostonUSA
  4. 4.Yerkes National Primate Research CenterEmory UniversityAtlantaUSA

Personalised recommendations