Brain Network Connectivity Mediates Education-related Cognitive Performance in Healthy Elderly Adults

Author(s): Yaojing Chen, Di Qi, Ting Qin, Kewei Chen, Meishan Ai, Xin Li, He Li, Junying Zhang, Haohao Mao, Yiru Yang, Zhanjun Zhang*

Journal Name: Current Alzheimer Research

Volume 16 , Issue 1 , 2019

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Background: Among the protective factors for cognitive decline related to aging and Alzheimer’s disease, education level is one of the most prominent. However, the mechanisms underlying the protective effects of education on cognition remain to be elucidated. In this study, we aimed to systematically assess the role of Functional Connectivity (FC) of resting-state brain networks playing in the cognition-protection effect of education.

Methods: Data from a battery of neuropsychological tests and functional magnetic resonance imaging in resting-state were acquired in 77 cognitively normal elderly participants from local communities in Beijing, China. Six resting-state networks related to primary function or complex cognition were extracted through independent component analysis. We then explored the relationships between education level, cognition, and FC of these networks.

Results: We found that education level was positively associated with a wide range of complex cognitive domains including general mental status, episodic memory, language, attention, executive function and visuospatial processing, and it showed significantly negative correlations with FC of multiple areas in the Default Mode Network (DMN) and Left Frontal-parietal Network (LFP) which are related to complex cognition. And regional connectivity of DMN was significantly negatively correlated with episodic memory performance. Further mediation analysis suggested that higher education level was associated with higher episodic memory performance through lower regional connectivity of DMN.

Conclusion: Our findings indicate that inhibitory modulation in the resting-state brain networks related to complex cognition is one of the main routes through which education exerts its protective effects on cognition in normal aging.

Keywords: Education, complex cognition, resting-state brain networks, functional connectivity, cognitive reserve, default mode network.

Luck T, Pabst A, Rodriguez FS, Schroeter ML, Witte V, Hinz A, et al. Age-, sex-, and education-specific norms for an extended CERAD Neuropsychological Assessment Battery-Results from the population-based LIFE-Adult-Study. Neuropsychology 32(4): 461-75. (2018).
Ihle A, Gouveia ER, Gouveia BR, Freitas DL, Jurema J, Odim AP, et al. The relation of education, occupation, and cognitive activity to cognitive status in old age: the role of physical frailty. Int Psychogeriatr 29(9): 1469-74. (2017).
Amieva H, Mokri H, Le Goff M, Meillon C, Jacqmin-Gadda H, Foubert-Samier A, et al. Compensatory mechanisms in higher-educated subjects with Alzheimer’s disease: a study of 20 years of cognitive decline. Brain 137(Pt 4): 1167-75. (2014).
Robitaille A, van den Hout A, Machado RJM, Bennett DA, Cukic I, Deary IJ, et al. Transitions across cognitive states and death among older adults in relation to education: a multistate survival model using data from six longitudinal studies. Alzheimers Dement 14(4): 462-72. (2018).
Brayne C, Ince PG, Keage HA, McKeith IG, Matthews FE, Polvikoski T, et al. Education, the brain and dementia: neuroprotection or compensation? Brain 133(Pt 8): 2210-6. (2010).
Zhang MY, Katzman R, Salmon D, Jin H, Cai GJ, Wang ZY, et al. The prevalence of dementia and Alzheimer’s disease in Shanghai, China: impact of age, gender, and education. Ann Neurol 27(4): 428-37. (1990).
Launer LJ, Andersen K, Dewey ME, Letenneur L, Ott A, Amaducci LA, et al. Rates and risk factors for dementia and Alzheimer’s disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. Eur Stud Dementia Neurology 52(1): 78-84. (1999).
Stern Y, Albert S, Tang MX, Tsai WY. Rate of memory decline in AD is related to education and occupation: cognitive reserve? Neurology 53(9): 1942-7. (1999).
Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc 8(3): 448-60. (2002).
Roe CM, Xiong C, Miller JP, Morris JC. Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis. Neurology 68(3): 223-8. (2007).
Bennett DA, Wilson RS, Schneider JA, Evans DA, Mendes de Leon CF, Arnold SE, et al. Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology 60(12): 1909-15. (2003).
Mortamais M, Portet F, Brickman AM, Provenzano FA, Muraskin J, Akbaraly TN, et al. Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia. Am J Geriatr Psychiatry 22(11): 1336-45. (2014).
Garibotto V, Borroni B, Kalbe E, Herholz K, Salmon E, Holtoff V, et al. Education and occupation as proxies for reserve in aMCI converters and AD: FDG-PET evidence. Neurology 71(17): 1342-9. (2018).
Foubert-Samier A, Catheline G, Amieva H, Dilharreguy B, Helmer C, Allard M, et al. Education, occupation, leisure activities, and brain reserve: a population-based study Neurobiol Aging 33(2): 423 e15-25 (2012).
Kim JP, Seo SW, Shin HY, Ye BS, Yang J-J, Kim C, et al. Effects of education on aging-related cortical thinning among cognitively normal individuals. Neurology 85(9): 806-12. (2015).
Arenaza-Urquijo EM, Landeau B, La Joie R, Mevel K, Mézenge F, Perrotin A, et al. Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders. Neuroimage 83: 450-7. (2013).
Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA 100(1): 253-8. (2003).
van den Heuvel MP, Hulshoff Pol HE. Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur Neuropsychopharmacol 20(8): 519-34. (2010).
Bozzali M, Dowling C, Serra L, Spano B, Torso M, Marra C, et al. The impact of cognitive reserve on brain functional connectivity in Alzheimer’s disease. J Alzheimers Dis 44(1): 243-50. (2015).
Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci 15(10): 483-506. (2011).
Heine L, Soddu A, Gomez F, Vanhaudenhuyse A, Tshibanda L, Thonnard M, et al. Resting state networks and consciousness: alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness States. Front Psychol 3: 295. (2012).
Damoiseaux J, Rombouts S, Barkhof F, Scheltens P, Stam C, Smith SM, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 103(37): 13848-53. (2006).
Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27(9): 2349-56. (2007).
Mejia S, Pineda D, Alvarez LM, Ardila A. Individual differences in memory and executive function abilities during normal aging. Int J Neurosci 95(3-4): 271-84. (1998).
Cullum S, Huppert FA, McGee M, Dening T, Ahmed A, Paykel ES, et al. Decline across different domains of cognitive function in normal ageing: results of a longitudinal population-based study using CAMCOG. Int J Geriatr Psychiatry 15(9): 853-62. (2000).
Mortby ME, Burns R, Janke AL, Sachdev PS, Anstey KJ, Cherbuin N. Relating education, brain structure, and cognition: the role of cardiovascular disease risk factors. BioMed Res Int 2014: 271487. (2014).
Parisi JM, Rebok GW, Xue QL, Fried LP, Seeman TE, Tanner EK, et al. The role of education and intellectual activity on cognition. J Aging Res 2012: 416132. (2012).
Chen Y, Chen K, Zhang J, Li X, Shu N, Wang J, et al. Disrupted functional and structural networks in cognitively normal elderly subjects with the apoe varepsilon4 allele. Neuropsychopharmacology 40(5): 1181-91. (2015).
Arenaza-Urquijo EM, Gonneaud J, Fouquet M, Perrotin A, Mézenge F, Landeau B, et al. Interaction between years of education and APOE ε4 status on frontal and temporal metabolism. Neurology 85(16): 1392-9. (2015).
Wang H-X, Gustafson DR, Kivipelto M, Pedersen NL, Skoog I, Windblad B, et al. Education halves the risk of dementia due to apolipoprotein ε4 allele: a collaborative study from the Swedish Brain Power initiativeNeurobiol Aging 33(5): 1007 e1-7 (2012).
Petersen RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 62(7): 1160-3. (2005).
Felsky D, Voineskos AN, Lerch JP, Nazeri A, Shaikh SA, Rajji TK, et al. Myelin-associated glycoprotein gene and brain morphometry in schizophrenia. Front Psychiatry 3: 40. (2012).
Hayes AF. Introduction to mediation, moderation, and conditional process analysis: A regression-based approachGuilford Press. (2013).
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124: 1-38. (2008).
Chai XJ, Ofen N, Gabrieli JD, Whitfield-Gabrieli S. Development of deactivation of the default-mode network during episodic memory formation. Neuroimage 84: 932-8. (2014).
Agosta F, Pievani M, Geroldi C, Copetti M, Frisoni GB, Filippi M. Resting state fMRI in Alzheimer’s disease: beyond the default mode network. Neurobiol Aging 33(8): 1564-78. (2012).
Hamzei F, Dettmers C, Rijntjes M, Glauche V, Kiebel S, Weber B, et al. Visuomotor control within a distributed parieto-frontal network. Exp Brain Res 146(3): 273-81. (2002).
Tripathi R, Kumar K, Bharath S, Marimuthu P, Varghese M. Age, education and gender effects on neuropsychological functions in healthy Indian older adults. Dement Neuropsychol 8(2): 148-54. (2014).
Li H, Lv C, Zhang T, Chen K, Chen C, Gai G, et al. Trajectories of age-related cognitive decline and potential associated factors of cognitive function in senior citizens of Beijing. Curr Alzheimer Res 11(8): 806-16. (2014).
Huang W, Zhou Y. Effects of education on cognition at older ages: evidence from China’s Great Famine. Soc Sci Med 98: 54-62. (2013).
de Souza-Talarico JN, Caramelli P, Nitrini R, Chaves EC. The influence of schooling on working memory performance in elderly individuals without cognitive decline. Dement Neuropsychol 1(3): 276-81. (2007).
Iavarone A, Lore E, De Falco C, Milan G, Mosca R, Pappata S, et al. Dysexecutive performance of healthy oldest old subjects on the Frontal Assessment Battery. Aging Clin Exp Res 23(5-6): 351-6. (2011).
Hashimoto R, Meguro K, Lee E, Kasai M, Ishii H, Yamaguchi S. Effect of age and education on the Trail Making Test and determination of normative data for Japanese elderly people: the Tajiri Project. Psychiatry Clin Neurosci 60(4): 422-8. (2006).
Stern Y. Cognitive reserve. Neuropsychologia 47(10): 2015-28. (2009).
Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol 11(11): 1006-12. (2012).
Franzmeier N, Gottler J, Grimmer T, Drzezga A, Araque-Caballero MA, Simon-Vermot L, et al. Resting-State connectivity of the left frontal cortex to the default mode and dorsal attention network supports reserve in mild cognitive impairment. Front Aging Neurosci 9: 264. (2017).
Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA 100(1): 253-8. (2003).
Gusnard DA, Raichle ME, Raichle ME. Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci 2(10): 685-94. (2001).
Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science 315(5810): 393-5. (2007).
Sestieri C, Corbetta M, Romani GL, Shulman GL. Episodic memory retrieval, parietal cortex, and the default mode network: functional and topographic analyses. J Neurosci 31(12): 4407-20. (2011).
Jeong W, Chung CK, Kim JS. Episodic memory in aspects of large-scale brain networks. Front Hum Neurosci 9: 454. (2015).
Rosenberg SJ, Ryan JJ, Prifitera A. Rey auditory-verbal learning test performance of patients with and without memory impairment. J Clin Psychol 40(3): 785-7. (1984).

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Year: 2019
Page: [19 - 28]
Pages: 10
DOI: 10.2174/1567205015666181022094158
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