Differential Effects of the Interaction Between the Education and APOE ε4 Allele on Amyloid-beta Retention and Memory Performances in Cognitively Normal Older Adults and Alzheimer's Disease Patients | Bentham Science
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

General Research Article

Differential Effects of the Interaction Between the Education and APOE ε4 Allele on Amyloid-beta Retention and Memory Performances in Cognitively Normal Older Adults and Alzheimer's Disease Patients

Author(s): Dong W. Kang, Sheng-Min Wang, Hae-Ran Na, Chang U. Lee, In-Ho Baek and Hyun K. Lim*

Volume 17, Issue 11, 2020

Page: [1023 - 1032] Pages: 10

DOI: 10.2174/1567205017666201229113416

open access plus

Open Access Journals Promotions 2
Abstract

Background: Despite the effect of education and APOE ε4 allele on amyloid-beta (Aβ) retention and memory, previous studies have not dealt with an interaction between two factors on Aβ deposition and memory function in the course of Alzheimer’s disease (AD).

Objective: To evaluate education by APOE ε4 allele interactions for Aβ retention and neuropsychological test scores in cognitively normal older adults without Aβ deposition [CN(Aβ-), n=45] and Alzheimer’s disease patients with Aβ retention [AD(Aβ+), n=33].

Methods: Multiple regression analyses (adjusted for age, gender) were conducted to examine the effects of education, APOE ε4 allele, and the interaction between the two factors on global, regional Aβ load quantified using [18F]flutemetamol standardized uptake value ratio with the pons as a reference region, and on neuropsychological test scores in each group.

Results: The interaction between education and APOE ε4 allele had an effect on amyloid load in parietal lobes (uncorrected p<0.05) and striatum (Bonferroni corrected p<0.05) in each CN(Aβ-) and AD(Aβ+). There was also an interaction effect of education and APOE ε4 allele on the memory performance in each CN(Aβ-) and AD(Aβ+) (uncorrected p<0.05). APOE ε4 carriers of both groups showed opposing slopes with each other in the correlation between the education years and Aβ load, memory performance.

Conclusion: The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.

Keywords: Education, APOE ε4 allele, amyloid load, memory performance, cognitive reserve, Alzheimer's disease, cognitively normal older adults.

[1]
Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol 2012; 11(11): 1006-12.
[http://dx.doi.org/10.1016/S1474-4422(12)70191-6] [PMID: 23079557]
[2]
Alexander GE, Furey ML, Grady CL, et al. Association of premorbid intellectual function with cerebral metabolism in Alzheimer’s disease: implications for the cognitive reserve hypothesis. Am J Psychiatry 1997; 154(2): 165-72.
[http://dx.doi.org/10.1176/ajp.154.2.165] [PMID: 9016263]
[3]
Perneczky R, Drzezga A, Diehl-Schmid J, et al. Schooling mediates brain reserve in Alzheimer’s disease: findings of fluoro-deoxy-glucose-positron emission tomography. J Neurol Neurosurg Psychiatry 2006; 77(9): 1060-3.
[http://dx.doi.org/10.1136/jnnp.2006.094714] [PMID: 16709580]
[4]
Stern Y, Alexander GE, Prohovnik I, Mayeux R. Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer’s disease. Ann Neurol 1992; 32(3): 371-5.
[http://dx.doi.org/10.1002/ana.410320311] [PMID: 1416806]
[5]
Meng X, D’Arcy C. Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses. PLoS One 2012; 7(6)e38268
[http://dx.doi.org/10.1371/journal.pone.0038268] [PMID: 22675535]
[6]
Stern Y, Tang MX, Denaro J, Mayeux R. Increased risk of mortality in Alzheimer’s disease patients with more advanced educational and occupational attainment. Ann Neurol 1995; 37(5): 590-5.
[http://dx.doi.org/10.1002/ana.410370508] [PMID: 7755353]
[7]
Stern Y, Albert S, Tang M-X, Tsai W-Y. Rate of memory decline in AD is related to education and occupation: cognitive reserve? Neurology 1999; 53(9): 1942-7.
[http://dx.doi.org/10.1212/WNL.53.9.1942] [PMID: 10599762]
[8]
Satz P, Morgenstern H, Miller EN, et al. Low education as a possible risk factor for cognitive abnormalities in HIV-1: findings from the multicenter AIDS Cohort Study (MACS). J Acquir Immune Defic Syndr (1988) 1993; 6(5): 503-11..
[PMID: 8483113]
[9]
Lo RY, Jagust WJ. Alzheimer’s Disease Neuroimaging Initiative. Effect of cognitive reserve markers on Alzheimer pathologic progression. Alzheimer Dis Assoc Disord 2013; 27(4): 343-50.
[http://dx.doi.org/10.1097/WAD.0b013e3182900b2b] [PMID: 23552443]
[10]
Vemuri P, Lesnick TG, Przybelski SA, et al. Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Ann Neurol 2012; 72(5): 730-8.
[http://dx.doi.org/10.1002/ana.23665] [PMID: 23280791]
[11]
Wirth M, Villeneuve S, La Joie R, Marks SM, Jagust WJ. Gene-environment interactions: lifetime cognitive activity, APOE genotype, and β-amyloid burden. J Neurosci 2014; 34(25): 8612-7.
[http://dx.doi.org/10.1523/JNEUROSCI.4612-13.2014] [PMID: 24948815]
[12]
Landau SM, Marks SM, Mormino EC, et al. Association of lifetime cognitive engagement and low β-amyloid deposition. Arch Neurol 2012; 69(5): 623-9.
[http://dx.doi.org/10.1001/archneurol.2011.2748] [PMID: 22271235]
[13]
Farrer LA, Cupples LA, Haines JL, et al. APOE and Alzheimer disease meta analysis Consortium. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA 1997; 278(16): 1349-56.
[http://dx.doi.org/10.1001/jama.1997.03550160069041] [PMID: 9343467]
[14]
Li C, Loewenstein DA, Duara R, Cabrerizo M, Barker W, Adjouadi M. Alzheimer’s Disease Neuroimaging Initiative. The relationship of brain amyloid load and APOE status to regional cortical thinning and cognition in the ADNI cohort. J Alzheimers Dis 2017; 59(4): 1269-82.
[http://dx.doi.org/10.3233/JAD-170286] [PMID: 28731444]
[15]
Solomon A, Mangialasche F, Richard E, et al. Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med 2014; 275(3): 229-50.
[http://dx.doi.org/10.1111/joim.12178] [PMID: 24605807]
[16]
Vemuri P, Lesnick TG, Przybelski SA, et al. Effect of intellectual enrichment on AD biomarker trajectories: longitudinal imaging study. Neurology 2016; 86(12): 1128-35.
[http://dx.doi.org/10.1212/WNL.0000000000002490] [PMID: 26911640]
[17]
Leal SL, Lockhart SN, Maass A, Bell RK, Jagust WJ. Subthreshold amyloid predicts tau deposition in aging. J Neurosci 2018; 38(19): 4482-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0485-18.2018] [PMID: 29686045]
[18]
Landau SM, Horng A, Jagust WJ. Alzheimer’s Disease Neuroimaging Initiative. Memory decline accompanies sub-threshold amyloid accumulation. Neurology 2018; 90(17): e1452-60.
[http://dx.doi.org/10.1212/WNL.0000000000005354] [PMID: 29572282]
[19]
Insel PS, Mattsson N, Mackin RS, et al. Alzheimer’s Disease Neuroimaging Initiative. Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology. Neurology 2016; 86(20): 1887-96.
[http://dx.doi.org/10.1212/WNL.0000000000002683] [PMID: 27164667]
[20]
Andel R, Vigen C, Mack WJ, Clark LJ, Gatz M. The effect of education and occupational complexity on rate of cognitive decline in Alzheimer’s patients. J Int Neuropsychol Soc 2006; 12(1): 147-52.
[http://dx.doi.org/10.1017/S1355617706060206] [PMID: 16433954]
[21]
Hall CB, Derby C, LeValley A, Katz MJ, Verghese J, Lipton RB. Education delays accelerated decline on a memory test in persons who develop dementia. Neurology 2007; 69(17): 1657-64.
[http://dx.doi.org/10.1212/01.wnl.0000278163.82636.30] [PMID: 17954781]
[22]
Lee JH, Lee KU, Lee DY, et al. Development of the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries. J Gerontol B Psychol Sci Soc Sci 2002; 57(1): 47-53.
[http://dx.doi.org/10.1093/geronb/57.1.P47] [PMID: 11773223]
[23]
Park J-H. Standardization of Korean version of the Mini-Mental State Examination (MMSE-K) for use in the elderly. Part II. Diagnostic validity. J Korean Neuropsychiatr Assoc 1989; 28: 508-13.
[24]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[25]
Morris JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type Int Psychogeriatr 1997; 9(S1)(1): 173-6..
[http://dx.doi.org/10.1017/S1041610297004870] [PMID: 9447441]
[26]
Choi SH, Shim YS, Ryu S-H, et al. Validation of the literacy independent cognitive assessment. Int Psychogeriatr 2011; 23(4): 593-601.
[http://dx.doi.org/10.1017/S1041610210001626] [PMID: 20843392]
[27]
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 2002; 15(1): 273-89.
[28]
Choi WH, Um YH, Jung WS. Kim SHJAonm Automated quantification of amyloid positron emission tomography: a comparison of PMOD and MIMneuro. 2016; 30(10): 682-89..
[29]
Buckley CJ, Sherwin PF, Smith AP, Wolber J, Weick SM, Brooks DJ. Validation of an electronic image reader training programme for interpretation of [18F]flutemetamol β-amyloid PET brain images. Nucl Med Commun 2017; 38(3): 234-41.
[http://dx.doi.org/10.1097/MNM.0000000000000633] [PMID: 27984539]
[30]
Vandenberghe R, Van Laere K, Ivanoiu A, et al. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol 2010; 68(3): 319-29.
[http://dx.doi.org/10.1002/ana.22068] [PMID: 20687209]
[31]
Team RC R. A language and environment for statistical computing 2013.
[32]
Arenaza-Urquijo EM, Wirth M, Chételat G. Cognitive reserve and lifestyle: moving towards preclinical Alzheimer’s disease. Front Aging Neurosci 2015; 7: 134.
[http://dx.doi.org/10.3389/fnagi.2015.00134] [PMID: 26321944]
[33]
Jagust WJ, Mormino EC. Lifespan brain activity, β-amyloid, and Alzheimer’s disease. Trends Cogn Sci 2011; 15(11): 520-6.
[http://dx.doi.org/10.1016/j.tics.2011.09.004] [PMID: 21983147]
[34]
Thal DR, Beach TG, Zanette M, et al. [(18)F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer’s disease: specific detection of advanced phases of amyloid-β pathology. Alzheimers Dement 2015; 11(8): 975-85.
[http://dx.doi.org/10.1016/j.jalz.2015.05.018] [PMID: 26141264]
[35]
Palmqvist S, Schöll M, Strandberg O, et al. Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nat Commun 2017; 8(1): 1214.
[http://dx.doi.org/10.1038/s41467-017-01150-x] [PMID: 29089479]
[36]
Costa DA, Cracchiolo JR, Bachstetter AD, et al. Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms. Neurobiol Aging 2007; 28(6): 831-44.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.04.009] [PMID: 16730391]
[37]
Lazarov O, Robinson J, Tang Y-P, et al. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 2005; 120(5): 701-13.
[http://dx.doi.org/10.1016/j.cell.2005.01.015] [PMID: 15766532]
[38]
Villemagne VL, Burnham S, Bourgeat P, et al. Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013; 12(4): 357-67.
[http://dx.doi.org/10.1016/S1474-4422(13)70044-9] [PMID: 23477989]
[39]
Scheinin NM, Aalto S, Koikkalainen J, et al. Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. Neurology 2009; 73(15): 1186-92.
[http://dx.doi.org/10.1212/WNL.0b013e3181bacf1b] [PMID: 19726751]
[40]
Kemppainen NM, Aalto S, Wilson IA, et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 2007; 68(19): 1603-6.
[http://dx.doi.org/10.1212/01.wnl.0000260969.94695.56] [PMID: 17485647]
[41]
Wilson RS, Hebert LE, Scherr PA, et al. Educational attainment and cognitive decline in old age. Neurology 2009; 72(5): 460-5.
[http://dx.doi.org/10.1212/01.wnl.0000341782.71418.6c] [PMID: 19188578]
[42]
Plassman BL, Welsh KA, Helms M, et al. Intelligence and education as predictors of cognitive state in late life: a 50-year follow-up. Neurology 1995; 45(8): 1446-50.
[http://dx.doi.org/10.1212/WNL.45.8.1446] [PMID: 7644038]
[43]
Resnick SM, Sojkova J, Zhou Y, et al. Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology 2010; 74(10): 807-15. [11C]..
[http://dx.doi.org/10.1212/WNL.0b013e3181d3e3e9] [PMID: 20147655]
[44]
Caselli RJ, Dueck AC, Osborne D, et al. Longitudinal modeling of age-related memory decline and the APOE ε4 effect. N Engl J Med 2009; 361(3): 255-63.
[45]
Kantarci K, Lowe V, Przybelski SA, et al. APOE modifies the association between Aβ load and cognition in cognitively normal older adults. Neurology 2012; 78(4): 232-40.
[http://dx.doi.org/10.1212/WNL.0b013e31824365ab] [PMID: 22189452]
[46]
Oliveira MM, Lourenco MV. Integrated stress response: connecting ApoE4 to memory impairment in Alzheimer’s disease. J Neurosci 2016; 36(4): 1053-5.
[http://dx.doi.org/10.1523/JNEUROSCI.4110-15.2016] [PMID: 26818496]
[47]
Arenaza-Urquijo EM, Landeau B, La Joie R, et al. Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders. Neuroimage 2013; 83: 450-7.
[http://dx.doi.org/10.1016/j.neuroimage.2013.06.053] [PMID: 23796547]
[48]
Sheline YI, Morris JC, Snyder AZ, et al. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. J Neurosci 2010; 30(50): 17035-40.
[http://dx.doi.org/10.1523/JNEUROSCI.3987-10.2010] [PMID: 21159973]
[49]
Maass A, Lockhart SN, Harrison TM, et al. Entorhinal tau pathology, episodic memory decline, and neurodegeneration in aging. J Neurosci 2018; 38(3): 530-43.
[http://dx.doi.org/10.1523/JNEUROSCI.2028-17.2017] [PMID: 29192126]
[50]
Wirth M, Madison CM, Rabinovici GD, Oh H, Landau SM. Jagust WJJJoN Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals. 2013; 33(13): 5553-63..
[51]
Groh N, Bühler A, Huang C, et al. Age-dependent protein aggregation initiates amyloid-β aggregation. Front Aging Neurosci 2017; 9: 138.
[http://dx.doi.org/10.3389/fnagi.2017.00138] [PMID: 28567012]
[52]
Seblova D, Berggren R, Lövdén M. Education and age-related decline in cognitive performance: Systematic review and meta-analysis of longitudinal cohort studies. Ageing Res Rev 2020; 58101005
[http://dx.doi.org/10.1016/j.arr.2019.101005] [PMID: 31881366]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy