Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus)

Abstract

Dual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human neurocognitive aging, yet the trajectory of dual decline has not been characterized. We therefore (1) assessed whether cognitive and physical performance (i.e., gait speed) are lower in older aged animals; (2) explored the relationship between performance in a novel task of executive function (Wake Forest Maze Task—WFMT) and a well-established assessment of working memory (delayed response task—DR task); and (3) examined the association between baseline gait speed with executive function and working memory at 1-year follow-up. We found (1) physical and cognitive declines with age; (2) strong agreement between performance in the novel WFMT and DR task; and (3) that slow gait is associated with poor cognitive performance in both domains. Our results suggest that older aged vervets exhibit a coordinated suite of traits consistent with human aging and that slow gait may be a biomarker of cognitive decline. This integrative approach provides evidence that gait speed and cognitive function differ across the lifespan in female vervet monkeys, which advances them as a model that could be used to dissect relationships between trajectories of dual decline over time.

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References

  1. 1.

    Statistics. National Center for Health Statistics. Health, United States, 2018. Hyattsville: Centers for Disease Control; 2019.

    Google Scholar 

  2. 2.

    Olshansky SJ. From lifespan to healthspan. JAMA. 2018;320(13):1323–4. https://doi.org/10.1001/jama.2018.12621.

    Article  PubMed  Google Scholar 

  3. 3.

    Dumurgier J, Elbaz A, Ducimetiere P, Tavernier B, Alperovitch A, Tzourio C. Slow walking speed and cardiovascular death in well functioning older adults: Prospective cohort study. BMJ. 2009;339(nov10 2):b4460–b. https://doi.org/10.1136/bmj.b4460.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50–8. https://doi.org/10.1001/jama.2010.1923.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Hoogendijk EO, Rijnhart JJM, Skoog J, Robitaille A, van den Hout A, Ferrucci L, et al. Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging. Exp Gerontol. 2020;129:110783. https://doi.org/10.1016/j.exger.2019.110783.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Okely JA, Deary IJ. Associations between declining physical and cognitive functions in the Lothian Birth Cohort 1936. J Gerontol A Biol Sci Med Sci. 2020;75(7):1393–402. https://doi.org/10.1093/gerona/glaa023.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Abellan van Kan G, Rolland Y, Gillette-Guyonnet S, Gardette V, Annweiler C, Beauchet O, et al. Gait speed, body composition, and dementia. The EPIDOS-Toulouse cohort. J Gerontol A Biol Sci Med Sci. 2012;67(4):425–32. https://doi.org/10.1093/gerona/glr177.

    Article  PubMed  Google Scholar 

  8. 8.

    Mielke MM, Roberts RO, Savica R, Cha R, Drubach DI, Christianson T, et al. Assessing the temporal relationship between cognition and gait: Slow gait predicts cognitive decline in the Mayo Clinic Study of Aging. J Gerontol A Biol Sci Med Sci. 2013;68(8):929–37. https://doi.org/10.1093/gerona/gls256.

    Article  PubMed  Google Scholar 

  9. 9.

    Waite LM, Grayson DA, Piguet O, Creasey H, Bennett HP, Broe GA. Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study. J Neurol Sci. 2005;229:89–93. https://doi.org/10.1016/j.jns.2004.11.009.

    Article  PubMed  Google Scholar 

  10. 10.

    Montero-Odasso M, Speechley M, Muir-Hunter SW, Pieruccini-Faria F, Sarquis-Adamson Y, Hachinski V, et al. Dual decline in gait speed and cognition is associated with future dementia: Evidence for a phenotype. Age Ageing. 2020;49:995–1002. https://doi.org/10.1093/ageing/afaa106.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Grande G, Haaksma ML, Rizzuto D, Melis RJF, Marengoni A, Onder G, et al. Co-occurrence of cognitive impairment and physical frailty, and incidence of dementia: Systematic review and meta-analysis. Neurosci Biobehav Rev. 2019;107:96–103. https://doi.org/10.1016/j.neubiorev.2019.09.001.

    Article  PubMed  Google Scholar 

  12. 12.

    Tian Q, Resnick SM, Mielke MM, Yaffe K, Launer LJ, Jonsson PV, et al. Association of dual decline in memory and gait speed with risk for dementia among adults older than 60 years: A multicohort individual-level meta-analysis. JAMA Netw Open. 2020;3(2):e1921636. https://doi.org/10.1001/jamanetworkopen.2019.21636.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Seo EH, Kim H, Lee KH, Choo IH. Altered executive function in pre-mild cognitive impairment. J Alzheimers Dis. 2016;54(3):933–40. https://doi.org/10.3233/JAD-160052.

    Article  PubMed  Google Scholar 

  14. 14.

    Kirova AM, Bays RB, Lagalwar S. Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease. Biomed Res Int. 2015;2015:748212–9. https://doi.org/10.1155/2015/748212.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Chai WJ, Abd Hamid AI, Abdullah JM. Working memory from the psychological and neurosciences perspectives: A review. Front Psychol. 2018;9:401. https://doi.org/10.3389/fpsyg.2018.00401.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Bocchi A, Carrieri M, Lancia C, Quaresima V, Piccardi L. The Key of the Maze: The role of mental imagery and cognitive flexibility in navigational planning. Neurosci Lett. 2017;651:146–50. https://doi.org/10.1016/j.neulet.2017.05.009.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Wray C, Kowalski A, Mpondo F, Ochaeta L, Belleza D, DiGirolamo A, et al. Executive functions form a single construct and are associated with schooling: Evidence from three low- and middle- income countries. PLoS One. 2020;15(11):e0242936. https://doi.org/10.1371/journal.pone.0242936.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Sakamoto K, Saito N, Yoshida S, Mushiake H. Dynamic axis-tuned cells in the monkey lateral prefrontal cortex during a path-planning task. J Neurosci. 2020;40(1):203–19. https://doi.org/10.1523/JNEUROSCI.2526-18.2019.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Handing E, Rapp S, Chen SH, Rejeski WJ, Wiberg M, Bandeen-Roche K, et al. Heterogeneity in association between cognitive function and gait speed among older adults: An integrative data analysis study. J Gerontol: Ser A. 2020;25:glaa211. https://doi.org/10.1093/gerona/glaa211.

    Article  Google Scholar 

  20. 20.

    Callisaya ML, Blizzard CL, Wood AG, Thrift AG, Wardill T, Srikanth VK. Longitudinal relationships between cognitive decline and gait slowing: The Tasmanian study of cognition and gait. J Gerontol A Biol Sci Med Sci. 2015;70(10):1226–32. https://doi.org/10.1093/gerona/glv066.

    Article  PubMed  Google Scholar 

  21. 21.

    Inzitari M, Newman AB, Yaffe K, Boudreau R, de Rekeneire N, Shorr R, et al. Gait speed predicts decline in attention and psychomotor speed in older adults: the health aging and body composition study. Neuroepidemiology. 2007;29(3-4):156–62. https://doi.org/10.1159/000111577.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Taniguchi Y, Yoshida H, Fujiwara Y, Motohashi Y, Shinkai S. A prospective study of gait performance and subsequent cognitive decline in a general population of older Japanese. J Gerontol A Biol Sci Med Sci. 2012;67(7):796–803. https://doi.org/10.1093/gerona/glr243.

    Article  PubMed  Google Scholar 

  23. 23.

    Rasmussen LJH, Caspi A, Ambler A, Broadbent JM, Cohen HJ, d'Arbeloff T, et al. Association of neurocognitive and physical function with gait speed in midlife. JAMA Netw Open. 2019;2(10):e1913123. https://doi.org/10.1001/jamanetworkopen.2019.13123.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Chou MY, Nishita Y, Nakagawa T, Tange C, Tomida M, Shimokata H, et al. Role of gait speed and grip strength in predicting 10-year cognitive decline among community-dwelling older people. BMC Geriatr. 2019;19(1):186. https://doi.org/10.1186/s12877-019-1199-7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Finkel D, Ernsth-Bravell M, Pedersen NL. Temporal dynamics of motor functioning and cognitive aging. J Gerontol A Biol Sci Med Sci. 2016;71(1):109–16. https://doi.org/10.1093/gerona/glv110.

    Article  PubMed  Google Scholar 

  26. 26.

    Best JR, Liu-Ambrose T, Boudreau RM, Ayonayon HN, Satterfield S, Simonsick EM, et al. An evaluation of the longitudinal, bidirectional associations between gait speed and cognition in older women and men. J Gerontol A Biol Sci Med Sci. 2016;71(12):1616–23. https://doi.org/10.1093/gerona/glw066.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Watson NL, Rosano C, Boudreau RM, Simonsick EM, Ferrucci L, Sutton-Tyrrell K, et al. Executive function, memory, and gait speed decline in well-functioning older adults. J Gerontol A Biol Sci Med Sci. 2010;65(10):1093–100. https://doi.org/10.1093/gerona/glq111.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Justice JN, Cesari M, Seals DR, Shively CA, Carter CS. Comparative approaches to understanding the relation between aging and physical function. J Gerontol A Biol Sci Med Sci. 2016;71(10):1243–53. https://doi.org/10.1093/gerona/glv035.

    Article  PubMed  Google Scholar 

  29. 29.

    Phillips KA, Bales KL, Capitanio JP, Conley A, Czoty PW. t Hart BA et al. Why primate models matter. Am J Primatol. 2014;76(9):801–27. https://doi.org/10.1002/ajp.22281.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Gray DT, Barnes CA. Experiments in macaque monkeys provide critical insights into age-associated changes in cognitive and sensory function. Proc Natl Acad Sci U S A. 2019;116:26247–54. https://doi.org/10.1073/pnas.1902279116.

    CAS  Article  PubMed Central  Google Scholar 

  31. 31.

    Darusman HS, Call J, Sajuthi D, Schapiro SJ, Gjedde A, Kalliokoski O, et al. Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis). Primates. 2014;55(2):259–67. https://doi.org/10.1007/s10329-013-0397-8.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Watson SL, Shively CA, Voytko ML. Can puzzle feeders be used as cognitive screening instruments? Differential performance of young and aged female monkeys on a puzzle feeder task. Am J Primatol. 1999;49:195–202.

    CAS  Article  Google Scholar 

  33. 33.

    Sadoun A, Rosito M, Fonta C, Girard P. Key periods of cognitive decline in a nonhuman primate model of cognitive aging, the common marmoset (Callithrix jacchus). Neurobiol Aging. 2019;74:1–14. https://doi.org/10.1016/j.neurobiolaging.2018.10.003.

    Article  PubMed  Google Scholar 

  34. 34.

    Joly M, Ammersdorfer S, Schmidtke D, Zimmermann E. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus). PLoS One. 2014;9(10):e109393. https://doi.org/10.1371/journal.pone.0109393.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Hopkins WD, Mareno MC, Webb SJN, Schapiro SJ, Raghanti MA, Sherwood CC. Age-related changes in chimpanzee (Pan troglodytes) cognition: Cross-sectional and longitudinal analyses. In: bioRxiv; 2020. https://doi.org/10.1101/2020.04.27.064626.

    Google Scholar 

  36. 36.

    Huber HF, Gerow KG, Nathanielsz PW. Walking speed as an aging biomarker in baboons (Papio hamadryas). J Med Primatol. 2015;44(6):373–80. https://doi.org/10.1111/jmp.12199.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Shively CA, Willard SL, Register TC, Bennett AJ, Pierre PJ, Laudenslager ML, et al. Aging and physical mobility in group-housed Old World monkeys. Age (Dordr). 2012;34(5):1123–31. https://doi.org/10.1007/s11357-011-9350-1.

    Article  Google Scholar 

  38. 38.

    Thompson ME, Machanda ZP, Fox SA, Sabbi KH, Otali E, Thompson Gonzalez N, et al. Evaluating the impact of physical frailty during ageing in wild chimpanzees (Pan troglodytes schweinfurthii). Philos Trans R Soc Lond Ser B Biol Sci. 2020;375(1811):20190607. https://doi.org/10.1098/rstb.2019.0607.

    Article  Google Scholar 

  39. 39.

    Yamada Y, Kemnitz JW, Weindruch R, Anderson RM, Schoeller DA, Colman RJ. Caloric restriction and healthy life span: Frail phenotype of nonhuman primates in the Wisconsin National Primate Research Center Caloric Restriction Study. J Gerontol A Biol Sci Med Sci. 2018;73(3):273–8. https://doi.org/10.1093/gerona/glx059.

    Article  PubMed  Google Scholar 

  40. 40.

    Appt SE, Ethun KF. Reproductive aging and risk for chronic disease: Insights from studies of nonhuman primates. Maturitas. 2010;67(1):7–14. https://doi.org/10.1016/j.maturitas.2010.03.028.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Jasinska AJ, Schmitt CA, Service SK, Cantor RM, Dewar K, Jentsch JD, et al. Systems biology of the vervet monkey. ILAR J. 2013;54(2):122–43. https://doi.org/10.1093/ilar/ilt049.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Cox LA, Olivier M, Spradling-Reeves K, Karere GM, Comuzzie AG, VandeBerg JL. Nonhuman primates and translational research-cardiovascular disease. ILAR J. 2017;58(2):235–50. https://doi.org/10.1093/ilar/ilx025.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Latimer CS, Shively CA, Keene CD, Jorgensen MJ, Andrews RN, Register TC, et al. A nonhuman primate model of early Alzheimer's disease pathologic change: Implications for disease pathogenesis. Alzheimers Dement. 2019;15(1):93–105. https://doi.org/10.1016/j.jalz.2018.06.3057.

    Article  PubMed  Google Scholar 

  44. 44.

    Neff EP. Animal models of Alzheimer’s disease embrace diversity. Lab Anim. 2019;48:255–9.

    Article  Google Scholar 

  45. 45.

    Allard M, Lèbre V, Robine JM, Calment J. Jeanne Calment: from Van Gogh's time to ours, 122 extraordinary years. New York: WH Freeman & Company; 1998.

    Google Scholar 

  46. 46.

    Weigl R. Longevity of mammals in captivity; from the Living Collections of the world: A list of mammalian longevity in captivity. Stuttgart: Kleine Senckenberg-Reihe; 2005.

    Google Scholar 

  47. 47.

    Justice JN, Silverstein-Metzler MG, Uberseder B, Appt SE, Clarkson TB, Register TC, et al. Relationships of depressive behavior and sertraline treatment with walking speed and activity in older female nonhuman primates. Geroscience. 2017;39(5-6):585–600. https://doi.org/10.1007/s11357-017-9999-1.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Beran MJ, Parrish AE, Futch SE, Evans TA, Perdue BM. Looking ahead? Computerized maze task performance by chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), capuchin monkeys (Cebus apella), and human children (Homo sapiens). J Comp Psychol. 2015;129(2):160–73. https://doi.org/10.1037/a0038936.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Kim K, Jeon H-A, Seo J, Park J, Won J, Yeo H-G, et al. Evaluation of cognitive function in adult rhesus monkeys using the finger maze test. Appl Anim Behav Sci. 2020;224:104945. https://doi.org/10.1016/j.applanim.2020.104945.

    Article  Google Scholar 

  50. 50.

    Tsuchida J, Kawasaki K, Sankai T, Kubo N, Terao K, Koyama T, et al. New type of puzzle-task finger maze learning in Macaca fascicularis. Int J Primatol. 2003;24(2):261–70. https://doi.org/10.1023/A:1023040931101.

    Article  Google Scholar 

  51. 51.

    Jacobsen CF. Functions of frontal association areas in primates. Arch Neurol Psychiatr. 1935;33:358–69.

    Article  Google Scholar 

  52. 52.

    Goldman PS, Rosvold HE, Vest B, Galkin TW. Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey. J Comp Physiol Psychol. 1971;77(2):212–20. https://doi.org/10.1037/h0031649.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    James AS, Groman SM, Seu E, Jorgensen M, Fairbanks LA, Jentsch JD. Dimensions of impulsivity are associated with poor spatial working memory performance in monkeys. J Neurosci. 2007;27(52):14358–64. https://doi.org/10.1523/JNEUROSCI.4508-07.2007.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Primates M, Altschul DM, Beran MJ, Bohn M, Call J, DeTroy S, et al. Establishing an infrastructure for collaboration in primate cognition research. PLoS One. 2019;14(10):e0223675. https://doi.org/10.1371/journal.pone.0223675.

    CAS  Article  Google Scholar 

  55. 55.

    Mattison JA, Vaughan KL. An overview of nonhuman primates in aging research. Exp Gerontol. 2017;94:41–5. https://doi.org/10.1016/j.exger.2016.12.005.

    Article  PubMed  Google Scholar 

  56. 56.

    Shively CA, Appt SA, Chen H, Day SM, Frye BM, Shaltout HA, et al. Mediterranean diet, stress resilience, and aging in nonhuman primates. Neurobiol Stress. 2020;13:100254. https://doi.org/10.1016/j.ynstr.2020.100254.

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Novak MA, Hamel AF, Kelly BJ, Dettmer AM, Meyer JS. Stress, the HPA axis, and nonhuman primate well-being: A review. Appl Anim Behav Sci. 2013;143(2-4):135–49. https://doi.org/10.1016/j.applanim.2012.10.012.

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Taylor JH, Mustoe AC, Hochfelder B, French JA. Reunion behavior after social separation is associated with enhanced HPA recovery in young marmoset monkeys. Psychoneuroendocrinology. 2015;57:93–101. https://doi.org/10.1016/j.psyneuen.2015.03.019.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Arnsten AF. Stress weakens prefrontal networks: molecular insults to higher cognition. Nat Neurosci. 2015;18(10):1376–85. https://doi.org/10.1038/nn.4087.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    McEwen BS, Sapolsky RM. Stress and cognitive function. Curr Opin Neurobiol. 1995;5:205–16. https://doi.org/10.1016/0959-4388(95)80028-X.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Lyons DM, Lopez JM, Yang C, Schatzberg AF. Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys. J Neurosci. 2000;20(20):7816–21.

    CAS  Article  Google Scholar 

  62. 62.

    Snyder-Mackler N, Sanz J, Kohn JN, Voyles T, Pique-Regi R, Wilson ME, et al. Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques. Proc Natl Acad Sci U S A. 2019;116(4):1219–28. https://doi.org/10.1073/pnas.1811758115.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Wittig RM, Crockford C, Weltring A, Langergraber KE, Deschner T, Zuberbuhler K. Social support reduces stress hormone levels in wild chimpanzees across stressful events and everyday affiliations. Nat Commun. 2016;7:13361. https://doi.org/10.1038/ncomms13361.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Guarino A, Forte G, Giovannoli J, Casagrande M. Executive functions in the elderly with mild cognitive impairment: a systematic review on motor and cognitive inhibition, conflict control and cognitive flexibility. Aging Ment Health. 2020;24(7):1028–45. https://doi.org/10.1080/13607863.2019.1584785.

    Article  PubMed  Google Scholar 

  65. 65.

    Guarino A, Favieri F, Boncompagni I, Agostini F, Cantone M, Casagrande M. Executive functions in Alzheimer disease: A systematic review. Front Aging Neurosci. 2019;10:437. https://doi.org/10.3389/fnagi.2018.00437.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Chrissy Long and Justin Herr for their advice and assistance during this study.

Funding

This work was supported by several mechanisms, including the following: National Institutes of Health (NIH) R01HL087103 (CAS), NIH RF1AG058829 (CAS & SC), P30 AG049638 (SC), Intramural Grant from the Department of Pathology, Wake Forest School of Medicine (CAS), Wake Forest Claude Pepper Older Americans Independence Center grant P30 AG21332 (SK), Vervet Research Colony (P40-OD010965) (MJ), and the Wake Forest Clinical and Translational Science Institute (NCATS UL1TR001420).

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Frye, B.M., Valure, P.M., Craft, S. et al. Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus). GeroScience (2021). https://doi.org/10.1007/s11357-021-00338-w

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Keywords

  • Nonhuman primate
  • Executive function
  • Working memory
  • Gait speed
  • Alzheimer’s disease