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Aging and disease    2016, Vol. 7 Issue (5) : 553-560     DOI: 10.14336/AD.2016.0305
Original Article |
Education and Genetic Risk Modulate Hippocampal Structure in Alzheimer’s Disease
Baumgaertel Johanna1, Haussmann Robert1, Gruschwitz Antonia1, Werner Annett3, Osterrath Antje1,2, Lange Jan1, Donix Katharina L.1, Linn Jennifer3, Donix Markus1,2,*
1Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
2DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany
3Department of Neuroradiology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
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Abstract  

Genetic and environmental protective factors and risks modulate brain structure and function in neurodegenerative diseases and their preclinical stages. We wanted to investigate whether the years of formal education, a proxy measure for cognitive reserve, would influence hippocampal structure in Alzheimer’s disease patients, and whether apolipoprotein Eε4 (APOE4) carrier status and a first-degree family history of the disease would change a possible association. Fifty-eight Alzheimer’s disease patients underwent 3T magnetic resonance imaging. We applied a cortical unfolding approach to investigate individual subregions of the medial temporal lobe. Among patients homozygous for the APOE4 genotype or carrying both APOE4 and family history risks, lower education was associated with a thinner cortex in multiple medial temporal regions, including the hippocampus. Our data suggest that the years of formal education and genetic risks interact in their influence on hippocampal structure in Alzheimer’s disease patients.

Keywords hippocampus      apolipoprotein E      cognitive reserve      education     
Corresponding Authors: Donix Markus   
About author:

These authors contributed equally to the work

Issue Date: 01 October 2016
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Baumgaertel Johanna
Haussmann Robert
Gruschwitz Antonia
Werner Annett
Osterrath Antje
Lange Jan
Donix Katharina L.
Linn Jennifer
Donix Markus
Cite this article:   
Baumgaertel Johanna,Haussmann Robert,Gruschwitz Antonia, et al. Education and Genetic Risk Modulate Hippocampal Structure in Alzheimer’s Disease[J]. Aging and disease, 2016, 7(5): 553-560.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2016.0305     OR     http://www.aginganddisease.org/EN/Y2016/V7/I5/553
Figure 1.  Cortical unfolding. After oblique coronal MRI scanning and manual segmentation of white matter and CSF on the T2 weighted MRI sequence, the resulting gray matter volume is computationally unfolded and flattened based on metric multidimensional scaling [right hemispheric flatmap shown, B]. Boundaries between the subregions are delineated on the original high-resolution MRI sequence (A) and later mathematically projected to flat map space. CA23DG=cornu ammonis fields 2,3 and dentate gyrus (the anterior part of the cornu ammonis fields and dentate gyrus [ant. CADG] is part of the CA23DG region), CA1=CA field 1, SUB=subiculum, ERC=entorhinal cortex, PRC=perirhinal cortex, PHC=parahippocampal cortex, FUS=fusiform cortex (fusiform boundary depicts the medial fusiform vertex).
Characteristics and MeasuresLower
education
SDHigher
education
SDSignificance
(p-value)*
N3226
Age (years)71.8± 7.073.8±6.30.25
Female sex (no.)1890.1
Education (years)11.5± 1.216.2±1.7< 0.001
APOE status (no.)
 2,3210.68
 3,31260.24
 3,413140.32
 4,4550.72
First degree family history of AD (no.)9130.09
MMSE (score range 0-30)21.1± 5.224.7± 4.20.033
Table 1  Demographic characteristics and neuropsychological scores.
Figure 2.  Correlation of education and cortical thickness. The figure illustrates the association of the years of education and cortical thickness across medial temporal subregions (legend see Figure 1). Patients homozygous for the APOE4 allele or APOE4 carriers with a first-degree family history of Alzheimer’s disease showed a positive correlation of education and thickness in all regions except CA1. Patients with an intermediate risk profile (APOE4 heterozygosis or family history risk) showed this correlation only in PHC with trends for other regions, such as the ERC. Patients in the low risk group (no APOE4 allele and no family history) did not show an association between education and thickness.
[1] Alzheimer’s disease facts and figures (2014). Alzheimers Dement, 10: e47-92
[2] Braak H, Braak E (1991). Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. (Berl). 82: 239-259
[3] Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, et al. (2006). Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry, 63: 168-174
[4] Li G, Silverman JM, Smith CJ, Zaccario ML, Schmeidler J, Mohs RC, et al. (1995). Age at onset and familial risk in Alzheimer’s disease. Am J Psychiatry, 152: 424-430
[5] Pedersen NL, Gatz M, Berg S, Johansson B (2004). How heritable is Alzheimer’s disease late in life? Findings from Swedish twins. Ann Neurol, 55: 180-185
[6] Fratiglioni L, Wang HX (2007). Brain reserve hypothesis in dementia. J Alzheimers Dis, 12: 11-22
[7] Stern Y (2006). Cognitive reserve and Alzheimer disease. Alzheimer Dis Assoc Disord., 20: 112-117
[8] Meng X, D’Arcy C (2012). Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses. PLoS One, 7: e38268
[9] Bickel H, Kurz A (2009). Education, occupation, and dementia: the Bavarian school sisters study. Dement Geriatr Cogn Disord, 27: 548-556
[10] Lo RY, Jagust WJ (2013). Effect of cognitive reserve markers on Alzheimer pathologic progression. Alzheimer Dis Assoc Disord., 27: 343-350
[11] Querbes O, Aubry F, Pariente J, Lotterie JA, Demonet JF, Duret V, et al. (2009). Early diagnosis of Alzheimer’s disease using cortical thickness: impact of cognitive reserve. Brain, 132: 2036-2047
[12] Sole-Padulles C, Bartres-Faz D, Junque C, Vendrell P, Rami L, Clemente IC, et al. (2009). Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging, 30: 1114-1124
[13] Serra L, Cercignani M, Petrosini L, Basile B, Perri R, Fadda L, et al. (2011). Neuroanatomical correlates of cognitive reserve in Alzheimer disease. Rejuvenation Res, 14: 143-151
[14] Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 261: 921-923
[15] Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, et al. (2000). Patterns of brain activation in people at risk for Alzheimer’s disease. N Engl J Med, 343: 450-456
[16] Shi J, Lepore N, Gutman BA, Thompson PM, Baxter LC, Caselli RJ, et al. (2014). Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface-based Alzheimer’s disease neuroimaging initiative study. Hum Brain Mapp, 35: 3903-3918
[17] Burggren AC, Zeineh MM, Ekstrom AD, Braskie MN, Thompson PM, Small GW, et al. (2008). Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers. Neuroimage, 41: 1177-1183
[18] Donix M, Small GW, Bookheimer SY (2012). Family History and APOE-4 Genetic Risk in Alzheimer’s Disease. Neuropsychol Rev, 22(3):298-309
[19] Cupples LA, Farrer LA, Sadovnick AD, Relkin N, Whitehouse P, Green RC (2004). Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: the REVEAL study. Genet Med, 6: 192-196
[20] Donix M, Burggren A, Suthana N, Siddarth P, Ekstrom A, Krupa A, et al. (2010). Family History of Alzheimer’s Disease and Hippocampal Structure in Healthy People. Am J Psychiatry, 167: 1399-1406
[21] Vermeiren AP, Bosma H, Visser PJ, Zeegers MP, Graff C, Ewers M, et al. (2013). The association between APOE epsilon4 and Alzheimer-type dementia among memory clinic patients is confined to those with a higher education. The DESCRIPA Study. J Alzheimers Dis, 35: 241-246
[22] Zeineh MM, Engel SA, Thompson PM, Bookheimer SY (2003). Dynamics of the hippocampus during encoding and retrieval of face-name pairs. Science, 299: 577-580
[23] Folstein MF, Folstein SE, McHugh PR (1975). Mini-Mental-State: a practical method for grading the cognitive state of patients for the clinician. J Psychiat Res, 12: 189-198
[24] McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34: 939-944
[25] Ekstrom AD, Bazih AJ, Suthana NA, Al-Hakim R, Ogura K, Zeineh MM, et al. (2009). Advances in high-resolution imaging and computational unfolding of the human hippocampus. Neuroimage, 47: 42-49
[26] Zeineh MM, Engel SA, Thompson PM, Bookheimer SY (2001). Unfolding the human hippocampus with high resolution structural and functional MRI. Anat Rec, 265: 111-120
[27] Teo PC, Sapiro G, Wandell BA (1997). Creating connected representations of cortical gray matter for functional MRI visualization. IEEE Trans. Med Imaging, 16: 852-863
[28] Amaral DG, Insausti R (1990). Hippocampal formation. In Paxinos G, editor. The Human Nervous System. San Diego: Academic Press, 711-755
[29] Duvernoy HM, editor. The Human Hippocampus: Functional Anatomy, Vascularization, and Serial Sections with MRI. Berlin: Springer; 1998
[30] Westman E, Aguilar C, Muehlboeck JS, Simmons A (2013). Regional magnetic resonance imaging measures for multivariate analysis in Alzheimer’s disease and mild cognitive impairment. Brain Topogr, 26: 9-23
[31] Bruandet A, Richard F, Bombois S, Maurage CA, Masse I, Amouyel P, et al. (2008). Cognitive decline and survival in Alzheimer’s disease according to education level. Dement. Geriatr. Cogn. Disord., 25: 74-80
[32] Gatz M, Mortimer JA, Fratiglioni L, Johansson B, Berg S, Andel R, et al. (2007). Accounting for the relationship between low education and dementia: a twin study. Physiol Behav, 92: 232-237
[33] Wang HX, Gustafson DR, Kivipelto M, Pedersen NL, Skoog I, Windblad B, et al. (2012). Education halves the risk of dementia due to apolipoprotein epsilon4 allele: a collaborative study from the Swedish brain power initiative. Neurobiol Aging, 33: 1007 e1-7
[34] Ngandu T, von Strauss E, Helkala EL, Winblad B, Nissinen A, Tuomilehto J, et al. (2007). Education and dementia: what lies behind the association? Neurology, 69: 1442-1450
[35] Soldan A, Pettigrew C, Lu Y, Wang MC, Selnes O, Albert M, et al. (2015). Relationship of medial temporal lobe atrophy, APOE genotype, and cognitive reserve in preclinical Alzheimer’s disease. Hum Brain Mapp, 36(7):2826-41
[36] Shaw P, Lerch JP, Pruessner JC, Taylor KN, Rose AB, Greenstein D, et al. (2007). Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurol, 6: 494-500
[37] Katzman R (1993). Education and the prevalence of dementia and Alzheimer’s disease. Neurology, 43: 13-20
[38] Borenstein AR, Copenhaver CI, Mortimer JA (2006). Early-life risk factors for Alzheimer disease. Alzheimer Dis Assoc Disord, 20: 63-72
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