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BMC Psychiatry
Published in: BMC Psychiatry 1/2014

Open Access 01-12-2014 | Research article

Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

Authors: Diddier Prada, Elena Colicino, Melinda C Power, David G Cox, Marc G Weisskopf, Lifang Hou, Avron Spiro III, Pantel Vokonas, Jia Zhong, Marco Sanchez-Guerra, Luis A Herrera, Joel Schwartz, Andrea A Baccarelli

Published in: BMC Psychiatry | Issue 1/2014

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Abstract

Background

APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations.

Methods

We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study.

Results

Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03).

Conclusions

These results suggest a beneficial effect of polymorphism rs429358 in the oldest men.
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Literature
1.
Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM: Monetary costs of dementia in the United States. N Engl J Med. 2013, 368: 1326-1334. 10.1056/NEJMsa1204629.CrossRefPubMedPubMedCentral
2.
Guralnik JM, Leveille SG, Hirsch R, Ferrucci L, Fried LP: The impact of disability in older women. J Am Med Womens Assoc. 1997, 52: 113-120.PubMed
3.
Thies W, Bleiler L, Association A’s: Alzheimer’s disease facts and figures. Alzheimers Dement. 2013, 2013 (9): 208-245.
4.
Bassuk SS, Wypij D, Berkman LF: Cognitive impairment and mortality in the community-dwelling elderly. Am J Epidemiol. 2000, 151: 676-688. 10.1093/oxfordjournals.aje.a010262.CrossRefPubMed
5.
Nguyen HT, Black SA, Ray LA, Espino DV, Markides KS: Cognitive impairment and mortality in older mexican americans. J Am Geriatr Soc. 2003, 51: 178-183. 10.1046/j.1532-5415.2003.51055.x.CrossRefPubMed
6.
Jorm AF, Jolley D: The incidence of dementia: a meta-analysis. Neurology. 1998, 51: 728-733. 10.1212/WNL.51.3.728.CrossRefPubMed
7.
Yang Y, Cao Z, Tian L, Garvey WT, Cheng G: VPO1 mediates ApoE oxidation and impairs the clearance of plasma lipids. PLoS ONE. 2013, 8: e57571-10.1371/journal.pone.0057571.CrossRefPubMedPubMedCentral
8.
Alexander DM, Williams LM, Gatt JM, Dobson-Stone C, Kuan SA, Todd EG, Schofield PR, Cooper NJ, Gordon E: The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades. Biol Psychol. 2007, 75: 229-238. 10.1016/j.biopsycho.2007.03.001.CrossRefPubMed
9.
Puttonen S, Elovainio M, Kivimäki M, Lehtimäki T, Keltikangas-Järvinen L: The combined effects of apolipoprotein E polymorphism and low-density lipoprotein cholesterol on cognitive performance in young adults. Neuropsychobiology. 2003, 48: 35-40. 10.1159/000071827.CrossRefPubMed
10.
Bloss CS, Delis DC, Salmon DP, Bondi MW: APOE genotype is associated with left-handedness and visuospatial skills in children. Neurobiol Aging. 2010, 31: 787-795. 10.1016/j.neurobiolaging.2008.05.021.CrossRefPubMed
11.
Carrión-Baralt JR, Meléndez-Cabrero J, Rodríguez-Ubiñas H, Schmeidler J, Beeri MS, Angelo G, Sano M, Silverman JM: Impact of APOE epsilon4 on the cognitive performance of a sample of non-demented Puerto Rican nonagenarians. J Alzheimers Dis. 2009, 18: 533-540.PubMed
12.
Artiga MJ, Bullido MJ, Sastre I, Recuero M, García MA, Aldudo J, Vázquez J, Valdivieso F: Allelic polymorphisms in the transcriptional regulatory region of apolipoprotein E gene. FEBS Lett. 1998, 421: 105-108. 10.1016/S0014-5793(97)01543-3.CrossRefPubMed
13.
Bray NJ, Jehu L, Moskvina V, Buxbaum JD, Dracheva S, Haroutunian V, Williams J, Buckland PR, Owen MJ, O’Donovan MC: Allelic expression of APOE in human brain: effects of epsilon status and promoter haplotypes. Hum Mol Genet. 2004, 13: 2885-2892. 10.1093/hmg/ddh299.CrossRefPubMed
14.
Artiga MJ, Bullido MJ, Frank A, Sastre I, Recuero M, García MA, Lendon CL, Han SW, Morris JC, Vázquez J, Goate A, Valdivieso F: Risk for Alzheimer’s disease correlates with transcriptional activity of the APOE gene. Hum Mol Genet. 1998, 7: 1887-1892. 10.1093/hmg/7.12.1887.CrossRefPubMed
15.
Bizzarro A, Seripa D, Acciarri A, Matera MG, Pilotto A, Tiziano FD, Brahe C, Masullo C: The complex interaction between APOE promoter and AD: an Italian case–control study. Eur J Hum Genet. 2009, 17: 938-945. 10.1038/ejhg.2008.263.CrossRefPubMedPubMedCentral
16.
Casadei VM, Ferri C, Veglia F, Gavazzi A, Salani G, Cattaneo M, Sorbi S, Annoni G, Licastro F, Mariani C, Franceschi M, Grimaldi LM: APOE-491 promoter polymorphism is a risk factor for late-onset Alzheimer’s disease. Neurology. 1999, 53: 1888-1889. 10.1212/WNL.53.8.1888.CrossRefPubMed
17.
Lescai F, Chiamenti AM, Codemo A, Pirazzini C, D’Agostino G, Ruaro C, Ghidoni R, Benussi L, Galimberti D, Esposito F, Marchegiani F, Cardelli M, Olivieri F, Nacmias B, Sorbi S, Tagliavini F, Albani D, Martinelli Boneschi F, Binetti G, Santoro A, Forloni G, Scarpini E, Crepaldi G, Gabelli C, Franceschi C: An APOE haplotype associated with decreased ε4 expression increases the risk of late onset Alzheimer's disease. J Alzheimers Dis. 2011, 24: 235-245.PubMed
18.
Viiri LE, Loimaala A, Nenonen A, Islam S, Vuori I, Karhunen PJ, Lehtimäki T: The association of the apolipoprotein E gene promoter polymorphisms and haplotypes with serum lipid and lipoprotein concentrations. Atherosclerosis. 2005, 179: 161-167. 10.1016/j.atherosclerosis.2004.10.004.CrossRefPubMed
19.
Tong TYY, Yong RYY, Goh VHH, Liang S, Chong APL, Mok HPP, Yong EL, Yap EPH, Moochhala S: Association between an intronic apolipoprotein E polymorphism and bone mineral density in Singaporean Chinese females. Bone. 2010, 47: 503-510. 10.1016/j.bone.2010.05.028.CrossRefPubMed
20.
Bell B, Rose CL, Damon A: The veterans administration longitudinal study of healthy aging. Gerontologist. 1966, 6: 179-184. 10.1093/geront/6.4.179.CrossRefPubMed
21.
Tombaugh TN, McIntyre NJ: The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992, ᅟ: ᅟ-
22.
Weisskopf MG, Proctor SP, Wright RO, Schwartz J, Spiro A, Sparrow D, Nie H, Hu H: Cumulative lead exposure and cognitive performance among elderly men. Epidemiology (Cambridge, Mass). 2007, 18: 59-66. 10.1097/01.ede.0000248237.35363.29.CrossRef
23.
Abner EL, Dennis BC, Mathews MJ, Mendiondo MS: Practice effects in a longitudinal, multi-center Alzheimer’s disease prevention clinical trial. Trials. 2012, ᅟ: ᅟ-
24.
Power MC, Weisskopf MG, Alexeeff SE, Coull BA, Spiro A, Schwartz J: Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect. 2010, 119: 682-687. 10.1289/ehp.1002767.CrossRefPubMedPubMedCentral
25.
Colicino E, Power MC, Cox DG, Weisskopf MG, Hou L, Alexeeff SE, Sanchez-Guerra M, Vokonas P, Spiro A, Schwartz J, Baccarelli AA: Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment. Environ Health. 2014, 13: 42-10.1186/1476-069X-13-42.CrossRefPubMedPubMedCentral
26.
Wright RO, Tsaih SW, Schwartz J, Spiro A, McDonald K, Weiss ST, Hu H: Lead exposure biomarkers and mini-mental status exam scores in older men. Epidemiology. 2003, 14: 713-718. 10.1097/01.EDE.0000081988.85964.db.CrossRefPubMed
27.
Mackin RS, Ayalon L, Feliciano L, Areán PA: The sensitivity and specificity of cognitive screening instruments to detect cognitive impairment in older adults with severe psychiatric illness. J Geriatr Psychiatry Neurol. 2010, 23: 94-99. 10.1177/0891988709358589.CrossRefPubMedPubMedCentral
28.
Aevarsson O, Skoog I: A longitudinal population study of the mini-mental state examination in the very old: relation to dementia and education. Dement Geriatr Cogn Disord. 2000, 11: 166-175. 10.1159/000017231.CrossRefPubMed
29.
Rusted JM, Evans SL, King SL, Dowell N, Tabet N, Tofts PS: APOE e4 polymorphism in young adults is associated with improved attention and indexed by distinct neural signatures. Neuroimage. 2013, 65: 364-373. 10.1016/j.neuroimage.2012.10.010.CrossRefPubMed
30.
Zlokovic BV: Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA Neurol. 2013, 70: 440-444. 10.1001/jamaneurol.2013.2152.CrossRefPubMedPubMedCentral
31.
Komurcu-Bayrak E, Onat A, Yuzbasiogullari B, Mononen N, Laaksonen R, Kähönen M, Hergenc G, Lehtimäki T, Erginel-Unaltuna N: The APOE -219G/T and +113G/C polymorphisms affect insulin resistance among Turks. Metab Clin Exp. 2011, 60: 655-663. 10.1016/j.metabol.2010.06.016.CrossRefPubMed
32.
Evans S, Dowell NG, Tabet N, Tofts PS, King SL, Rusted JM: Cognitive and neural signatures of the APOE E4 allele in mid-aged adults. Neurobiol Aging. 2014, 35: 1615-1623. 10.1016/j.neurobiolaging.2014.01.145.CrossRefPubMedPubMedCentral
33.
Valerio D, Raventos H, Schmeidler J, Beeri MS, Villalobos LM, Bolaños-Palmieri P, Carrión-Baralt JR, Fornaguera J, Silverman JM: Association of apolipoprotein E-e4 and dementia declines with age. Am J Geriatr Psychiatry. 2014, ᅟ: ᅟ-
34.
Corrada MM, Paganini-Hill A, Berlau DJ, Kawas CH: Apolipoprotein E genotype, dementia, and mortality in the oldest old: the 90+ study. Alzheimers Dement. 2013, 9: 12-18. 10.1016/j.jalz.2011.12.004.CrossRefPubMed
35.
Jellinger KA, Attems J: Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol. 2010, 119: 421-433. 10.1007/s00401-010-0654-5.CrossRefPubMed
36.
Kulminski AM, Culminskaya I, Arbeev KG, Ukraintseva SV, Stallard E, Arbeeva L, Yashin AI: The role of lipid-related genes, aging-related processes, and environment in healthspan. Aging Cell. 2013, 12: 237-246. 10.1111/acel.12046.CrossRefPubMedPubMedCentral
37.
Utermann G, Hardewig A, Zimmer F: Apolipoprotein E phenotypes in patients with myocardial infarction. Hum Genet. 1984, 65: 237-241. 10.1007/BF00286509.CrossRefPubMed
38.
Kawas CH, Corrada MM: Alzheimer’s and dementia in the oldest-old: a century of challenges. Curr Alzheimer Res. 2006, 3: 411-419. 10.2174/156720506779025233.CrossRefPubMedPubMedCentral
39.
Holland D, Desikan RS, Dale AM, McEvoy LK: Higher rates of decline for women and apolipoprotein E epsilon4 carriers. AJNR Am J Neuroradiol. 2013, 34: 2287-2293. 10.3174/ajnr.A3601.CrossRefPubMedPubMedCentral
40.
Han SD, Drake AI, Cessante LM, Jak AJ, Houston WS, Delis DC, Filoteo JV, Bondi MW: Apolipoprotein E and traumatic brain injury in a military population: evidence of a neuropsychological compensatory mechanism?. J Neurol Neurosurg Psychiatr. 2007, 78: 1103-1108. 10.1136/jnnp.2006.108183.CrossRefPubMedPubMedCentral
41.
Acevedo SF, Piper BJ, Craytor MJ, Benice TS, Raber J: Apolipoprotein E4 and sex affect neurobehavioral performance in primary school children. Pediatr Res. 2010, 67: 293-299. 10.1203/PDR.0b013e3181cb8e68.CrossRefPubMedPubMedCentral
42.
Mortensen EL, Høgh P: A gender difference in the association between APOE genotype and age-related cognitive decline. Neurology. 2001, 57: 89-95. 10.1212/WNL.57.1.89.CrossRefPubMed
43.
Mondadori CRA, de Quervain DJ-F, Buchmann A, Mustovic H, Wollmer MA, Schmidt CF, Boesiger P, Hock C, Nitsch RM, Papassotiropoulos A, Henke K: Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. Cereb Cortex. 2007, 17: 1934-1947. 10.1093/cercor/bhl103.CrossRefPubMed
44.
Marchant NL, King SL, Tabet N, Rusted JM: Positive effects of cholinergic stimulation favor young APOE ϵ4 carriers. Neuropsychopharmacology. 2010, 35: 1090-1096. 10.1038/npp.2009.214.CrossRefPubMedPubMedCentral
45.
Han SD, Bondi MW: Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis. Alzheimers Dement. 2008, 4: 251-254. 10.1016/j.jalz.2008.02.006.CrossRefPubMed
46.
Ihle A, Bunce D, Kliegel M: APOE ε4 and cognitive function in early life: a meta-analysis. Neuropsychology. 2012, 26: 267-277. 10.1037/a0026769.CrossRefPubMed
47.
Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM: Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis: APOE and Alzheimer disease meta analysis Consortium. JAMA. 1997, 278: 1349-1356. 10.1001/jama.1997.03550160069041.CrossRefPubMed
48.
Tang MX, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L, Tycko B, Mayeux R: The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998, 279: 751-755. 10.1001/jama.279.10.751.CrossRefPubMed
49.
Pettigrew C, Soldan A, Li S, Lu Y, Wang MC: Relationship of cognitive reserve and APOE status to the emergence of clinical symptoms in preclinical Alzheimer’s disease. Cognitive. 2013, ᅟ: ᅟ-
50.
Berr C, Dufouil C, Brousseau T, Richard F, Amouyel P, Marceteau E, Alpérovitch A: Early effect of ApoE-epsilon 4 allele on cognitive results in a group of highly performing subjects: the EVA study: Etude sur le Vieillissement Artériel. Neurosci Lett. 1996, 218: 9-12.CrossRefPubMed
51.
De Blasi S, Montesanto A, Martino C, Dato S, De Rango F, Bruni AC, Mari V, Feraco E, Passarino G: APOE polymorphism affects episodic memory among non demented elderly subjects. Exp Gerontol. 2009, 44: 224-227. 10.1016/j.exger.2008.11.005.CrossRefPubMed
52.
Driscoll I, McDaniel MA, Guynn MJ: Apolipoprotein E and prospective memory in normally aging adults. Neuropsychology. 2005, 19: 28-34. 10.1037/0894-4105.19.1.28.CrossRefPubMed
Metadata
Title
Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study
Authors
Diddier Prada
Elena Colicino
Melinda C Power
David G Cox
Marc G Weisskopf
Lifang Hou
Avron Spiro III
Pantel Vokonas
Jia Zhong
Marco Sanchez-Guerra
Luis A Herrera
Joel Schwartz
Andrea A Baccarelli
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2014
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-014-0223-x

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