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Volume of the hippocampal subfields in healthy adults: differential associations with age and a pro-inflammatory genetic variant

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Abstract

The hippocampus is one of the most age-sensitive brain regions, yet the mechanisms of hippocampal shrinkage remain unclear. Recent studies suggest that hippocampal subfields are differentially vulnerable to aging and differentially sensitive to vascular risk. Promoters of inflammation are frequently proposed as major contributors to brain aging and vascular disease but their effects on hippocampal subfields are unknown. We examined the associations of hippocampal subfield volumes with age, a vascular risk factor (hypertension), and genetic polymorphisms associated with variation in pro-inflammatory cytokines levels (IL-1β C-511T and IL-6 C-174G) and risk for Alzheimer’s disease (APOEε4) in healthy adult volunteers (N = 80; age = 22–82 years). Volumes of three hippocampal subfields, cornu ammonis (CA) 1–2, CA3–dentate gyrus, and the subiculum were manually measured on high-resolution magnetic resonance images. Advanced age was differentially associated with smaller volume of CA1–2, whereas carriers of the T allele of IL-1β C-511T polymorphism had smaller volume of all hippocampal subfields than CC homozygotes did. Neither of the other genetic variants, nor diagnosis of hypertension, was associated with any of the measured volumes. The results support the notion that volumes of age-sensitive brain regions may be affected by pro-inflammatory factors that may be targeted by therapeutic interventions.

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References

  • Adamson M, Landy KM, Duong S, Fox-Bosetti S, Ashford JW, Murphy GM, Weiner M, Taylor JL (2010) Apolipoprotein E epsilon4 influences on episodic recall and brain structures in aging pilots. Neurobiol Aging 31:1059–1063. doi:10.1016/j.neurobiolaging.2008.07.017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Arisi GM (2014) Nervous and immune systems signals and connections: cytokines in hippocampus physiology and pathology. Epilepsy Behav. doi:10.1016/j.yebeh.2014.01.017

  • Ban E, Milon G, Prudhomme N, Fillion G, Haour F (1991) Receptors for interleukin-1 (alpha and beta) in mouse brain: mapping and neuronal localization in hippocampus. Neuroscience 43:21–30

    Article  CAS  PubMed  Google Scholar 

  • Banks WA (2005) Blood–brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des 11:973–984

    Article  CAS  PubMed  Google Scholar 

  • Banks WA, Kastin AJ, Broadwell RD (1995) Passage of cytokines across the blood–brain barrier. Neuroimmunomodulation 2:241–248

    Article  CAS  PubMed  Google Scholar 

  • Banks WA, Farr SA, La Scola ME, Morley JE (2001) Intravenous human interleukin-1 alpha impairs memory processing in mice: dependence on blood–brain barrier transport into posterior division of the septum. J Pharmacol Exp Ther 299:536–541

    CAS  PubMed  Google Scholar 

  • Bartsch T, Döhring J, Rohr A, Jansen O, Deuschl G (2011) CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness. Proc Natl Acad Sci USA 108:17562–17567. doi:10.1073/pnas.1110266108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baune BT, Konrad C, Grotegerd D, Suslow T, Birosova E, Ohrmann P, Bauer J, Arolt V, Heindel W, Domschke K, Schöning S, Rauch AV, Uhlmann C, Kugel H, Dannlowski U (2012) Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain. J Neuroinflamm 9:125. doi:10.1186/1742-2094-9-125

    Article  CAS  Google Scholar 

  • Bender AR, Raz N (2012) Age-related differences in memory and executive functions in healthy APOE ε4 carriers: the contribution of individual differences in prefrontal volumes and systolic blood pressure. Neuropsychologia 50:704–714. doi:10.1016/j.neuropsychologia.2011.12.025

    Article  PubMed Central  PubMed  Google Scholar 

  • Blasko I, Stampfer-Kountchev M, Robatscher P, Veerhuis R, Eikelenboom P, Grubeck-Loebenstein B (2004) How chronic inflammation can affect the brain and support the development of Alzheimer’s disease in old age: the role of microglia and astrocytes. Aging Cell 3:169–176

    Article  CAS  PubMed  Google Scholar 

  • Bobinski M, de Leon MJ, Wegiel J, Desanti S, Convit A, Saint Louis LA, Rusinek H, Wisniewski HM (2000) The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer’s disease. Neuroscience 95:721–725

    Article  CAS  PubMed  Google Scholar 

  • Burns JM, Honea RA, Vidoni ED, Hutfles LJ, Brooks WM, Swerdlow RH (2012) Insulin is differentially related to cognitive decline and atrophy in Alzheimer’s disease and aging. Biochim Biophys Acta 1822:333–339. doi:10.1016/j.bbadis.2011.06.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cherbuin N, Anstey KJ, Sachdev PS, Maller JJ, Meslin C, Mack HA, Wen W, Easteal S (2008) Total and regional gray matter volume is not related to APOE*E4 status in a community sample of middle-aged individuals. J Gerontol A Biol Sci Med Sci 63:501–504

    Article  PubMed  Google Scholar 

  • Cherbuin N, Sachdev P, Anstey KJ (2012) Higher normal fasting plasma glucose is associated with hippocampal atrophy: the PATH Study. Neurology 79:1019–1026. doi:10.1212/WNL.0b013e31826846de

    Article  PubMed  Google Scholar 

  • Chiang GC, Insel PS, Tosun D, Schuff N, Truran-Sacrey D, Raptentsetsang ST, Thompson PM, Reiman EM, Jack CR Jr, Fox NC, Jagust WJ, Harvey DJ, Beckett LA, Gamst A, Aisen PS, Petersen RC, Weiner MW, Alzheimer’s Disease Neuroimaging Initiative (2011) Impact of apolipoprotein E4-cerebrospinal fluid β-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment. Alzheimers Dement 7:514–520. doi:10.1016/j.jalz.2010.12.010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cohen RM, Small C, Lalonde F, Friz J, Sunderland T (2001) Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women. Neurology 57:2223–2228

    Article  CAS  PubMed  Google Scholar 

  • Crivello F, Lemaître H, Dufouil C, Grassiot B, Delcroix N, Tzourio-Mazoyer N, Tzourio C, Mazoyer B (2010) Effects of ApoE-epsilon4 allele load and age on the rates of grey matter and hippocampal volumes loss in a longitudinal cohort of 1186 healthy elderly persons. Neuroimage 53:1064–1069. doi:10.1016/j.neuroimage.2009.12.116

    Article  CAS  PubMed  Google Scholar 

  • Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8:1–21

    Article  CAS  PubMed  Google Scholar 

  • den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, Breteler MM (2003) Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 126:170–175

    Article  Google Scholar 

  • den Heijer T, van der Lijn F, Ikram A, Koudstaal PJ, van der Lugt A, Krestin GP, Vrooman HA, Hofman A, Niessen WJ, Breteler MM (2012) Vascular risk factors, apolipoprotein E, and hippocampal decline on magnetic resonance imaging over a 10-year follow-up. Alzheimers Dement 8:417–425. doi:10.1016/j.jalz.2011.07.005

    Article  CAS  Google Scholar 

  • Di Bona D, Plaia A, Vasto S, Cavallone L, Lescai F, Franceschi C, Licastro F, Colonna-Romano G, Lio D, Candore G, Caruso C (2008) Association between the interleukin-1beta polymorphisms and Alzheimer’s disease: a systematic review and meta-analysis. Brain Res Rev 59:155–163. doi:10.1016/j.brainresrev.2008.07.003

    Article  PubMed  CAS  Google Scholar 

  • Di Filippo M, Chiasserini D, Gardoni F, Viviani B, Tozzi A, Giampà C, Costa C, Tantucci M, Zianni E, Boraso M, Siliquini S, de lure A, Ghiglieri V, Colcelli E, Baker D, Sarchielli P, Fusco FR, Di Luca M, Calabresi P (2013) Effects of central and peripheral inflammation on hippocampal synaptic plasticity. Neurobiol Dis 52:229–236. doi:10.1016/j.nbd.2012.12.009

    Article  PubMed  CAS  Google Scholar 

  • Ekdahl CT, Kokaia Z, Lindvall O (2009) Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 158:1021–1029. doi:10.1016/j.neuroscience.2008.06.052

    Article  CAS  PubMed  Google Scholar 

  • Ferencz B, Laukka EJ, Lövdén M, Kalpouzos G, Keller L, Graff C, Wahlund LO, Fratiglioni L, Bäckman L (2013) The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age. Front Hum Neurosci 7:198. doi:10.3389/fnhum.2013.00198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Finch CE, Crimmins EM (2004) Inflammatory exposure and historical changes in human life-spans. Science 305:1736–1739

    Article  CAS  PubMed  Google Scholar 

  • Finch CE, Foster JR, Mirsky AE (1969) Ageing and the regulation of cell activities during exposure to cold. J Gen Physiol 54:690–712

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

    Article  CAS  PubMed  Google Scholar 

  • Franklin SS, Gustin WT, Wong ND, Larson MG, Weber MA, Kannel WB, Levy D (1997) Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 96:308–315

    Article  CAS  PubMed  Google Scholar 

  • Gomes da Silva S, Simões PS, Mortara RA, Scorza FA, Cavalheiro EA, da Graça Naffah-Mazzacoratti M, Arida RM (2013) Exercise-induced hippocampal anti-inflammatory response in aged rats. J Neuroinflammation 10:61. doi:10.1186/1742-2094-10-61

  • Graeber MB, Li W, Rodriguez MI (2011) Role of microglia in CNS inflammation. FEBS Lett 585:3798–3805

    Article  CAS  PubMed  Google Scholar 

  • Grammas P (2011) Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J Neuroinflamm 8:26. doi:10.1186/1742-2094-8-26

    Article  CAS  Google Scholar 

  • Griffin WS, Mrak RE (2002) Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer’s disease. J Leukoc Biol 72:233–238

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guo JT, Yu J, Grass D, de Beer FC, Kindy MS (2002) Inflammation-dependent cerebral deposition of serum amyloid a protein in a mouse model of amyloidosis. J Neurosci 22:5900–5909

    CAS  PubMed  Google Scholar 

  • Harry GJ, d’Hellencourt CL (2003) Dentate gyrus: alterations that occur with hippocampal injury. Neurotoxicology 24:343–356

    Article  PubMed  Google Scholar 

  • Hauss-Wegrzyniak B, Galons JP, Wenk GL (2000) Quantitative volumetric analyses of brain magnetic resonance imaging from rat with chronic neuroinflammation. Exp Neurol 165:347–354

    Article  CAS  PubMed  Google Scholar 

  • Hayes A, Green EK, Pritchard A, Harris JM, Zhang Y, Lambert JC, Chartier-Harlin MC, Pickering-Brown SM, Lendon CL, Mann DM (2004) A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:1475–1477

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hildrum B, Mykletun A, Hole T, Midthjell K, Dahl AA (2007) Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program: the Norwegian HUNT 2 study. BMC Public Health 7:220

    Article  PubMed Central  PubMed  Google Scholar 

  • Hof PR, Morrison JH (1996) Hippocampal and neocortical involvement in normal brain aging and dementia: morphological and neurochemical profile of the vulnerable circuits. J Am Geriatr Soc 44:857–864

    Article  CAS  PubMed  Google Scholar 

  • Hostage CA, Roy Choudhury K, Doraiswamy PM, Petrella JR, Alzheimer’s Disease Neuroimaging Initiative (2013) Dissecting the gene dose-effects of the APOE ε4 and ε2 alleles on hippocampal volumes in aging and Alzheimer’s disease. PLoS One 8:e54483. doi:10.1371/journal.pone.0054483

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huang ZB, Sheng GQ (2010) Interleukin-1beta with learning and memory. Neurosci Bull 26:455–468

    Article  CAS  PubMed  Google Scholar 

  • Hurme M, Santtila S (1998) IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1β genes. Eur J Immunol 28:2598–2602

    Article  CAS  PubMed  Google Scholar 

  • Jenkinson M, Pechaud M, Smith S (2005) BET2: MR-based estimation of brain, skull and scalp surfaces. In: The Proceedings from the eleventh annual meeting of the organization for human brain mapping, Toronto, Ontario, Canada

  • Jurgens HA, Johnson RW (2012) Dysregulated neuronal-microglial cross-talk during aging, stress and inflammation. Exp Neurol 233:40–48. doi:10.1016/j.expneurol.2010.11.014

    Article  PubMed Central  PubMed  Google Scholar 

  • Katan MB (1986) Apolipoprotein E isoforms, serum cholesterol, and cancer. Lancet 1:507–508

    Article  CAS  PubMed  Google Scholar 

  • Kauffman MA, Moron DG, Consalvo D, Bello R, Kochen S (2008) Association study between interleukin 1 beta gene and epileptic disorders: a HuGe review and meta-analysis. Genet Med 10:83–88. doi:10.1097/GIM.0b013e318161317c

    Article  CAS  PubMed  Google Scholar 

  • Keihaninejad S, Heckemann RA, Fagiolo G, Symms MR, Hajnal JV, Hammers A (2010) A robust method to estimate the intracranial volume across MRI field strengths (1.5T and 3T). Neuroimage 50:1427–1437. doi:10.1016/j.neuroimage.2010.01.064

    Article  PubMed Central  PubMed  Google Scholar 

  • Kerchner GA, Bernstein JD, Fenesy MC, Deutsch GK, Saranathan M, Zeineh MM, Rutt BK (2013) Shared vulnerability of two synaptically-connected medial temporal lobe areas to age and cognitive decline: a seven tesla magnetic resonance imaging study. J Neurosci 33:16666–16672. doi:10.1523/JNEUROSCI.1915-13.2013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kesner RP (2007) Behavioral functions of the CA3 subregion of the hippocampus. Learn Mem 14:771–781

    Article  PubMed  Google Scholar 

  • Konsman JP, Kelley K, Dantzer R (1999) Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain. Neuroscience 89:535–548

    Article  CAS  PubMed  Google Scholar 

  • Koo JW, Duman RS (2008) IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci USA 105:751–756. doi:10.1073/pnas.0708092105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Korf ES, White LR, Scheltens P, Launer LJ (2004) Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia Aging Study. Hypertension 44:29–34

    Article  CAS  PubMed  Google Scholar 

  • Kriz J, Lalancette-Hébert M (2009) Inflammation, plasticity and real-time imaging after cerebral ischemia. Acta Neuropathol 117:497–509. doi:10.1007/s00401-009-0496-1

    Article  CAS  PubMed  Google Scholar 

  • La Joie R, Fouquet M, Mézenge F, Landeau B, Villain N, Mevel K, Pélerin A, Eustache F, Desgranges B, Chételat G (2010) Differential effect of age on hippocampal subfields assessed using a new high-resolution 3T MR sequence. Neuroimage 53:506–514. doi:10.1016/j.neuroimage.2010.06.024

    Article  PubMed  Google Scholar 

  • Lawlor DA, Harbord RM, Sternej AC, Timpson N, Davey Smith G (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27:1133–1163

    Article  PubMed  Google Scholar 

  • Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, Hong JT (2008) Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflamm 5:37. doi:10.1186/1742-2094-5-37

    Article  CAS  Google Scholar 

  • Lemaître H, Crivello F, Dufouil C, Grassiot B, Tzourio C, Alpérovitch A, Mazoyer B (2005) No epsilon4 gene dose effect on hippocampal atrophy in a large MRI database of healthy elderly subjects. Neuroimage 24:1205–1213

    Article  PubMed  Google Scholar 

  • Lind J, Larsson A, Persson J, Ingvar M, Nilsson LG, Bäckman L, Adolfsson R, Cruts M, Sleegers K, Van Broeckhoven C, Nyberg L (2006) Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory. Neurosci Lett 396:23–27

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Wu Z, Hayashi Y, Nakanishi H (2012) Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation. Neuroscience 216:133–142. doi:10.1016/j.neuroscience.2012.04.050

    Article  CAS  PubMed  Google Scholar 

  • Lu PH, Thompson PM, Leow A, Lee GJ, Lee A, Yanovsky I, Parikshak N, Khoo T, Wu S, Geschwind D, Bartzokis G (2011) Apolipoprotein E genotype is associated with temporal and hippocampal atrophy rates in healthy elderly adults: a tensor-based morphometry study. J Alzheimers Dis 23:433–442. doi:10.3233/JAD-2010-101398

    PubMed Central  PubMed  Google Scholar 

  • Lynch MA (1998) Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1 beta? Prog Neurobiol 56:571–589

    Article  CAS  PubMed  Google Scholar 

  • Mahley R (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240:622–640

    Article  CAS  PubMed  Google Scholar 

  • Marsland AL, Gianaros PJ, Abramowitch SM, Manuck SB, Hariri AR (2008) Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biol Psychiatry 64:484–490. doi:10.1016/j.biopsych

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Meisenzahl EM, Rujescu D, Kirner A, Giegling I, Kathmann N, Leinsinger G, Maag K, Hegerl U, Hahn K, Möller HJ (2001) Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia. Am J Psychiatry 158:1316–1319

    Article  CAS  PubMed  Google Scholar 

  • Moffat SD, Szekely CA, Zonderman AB, Kabani NJ, Resnick SM (2000) Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype. Neurology 55:134–136

    Article  CAS  PubMed  Google Scholar 

  • Mu Q, Xie J, Wen Z, Weng Y, Shuyun Z (1999) A quantitative MR study of the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle in healthy subjects 40 to 90 years of age. AJNR Am J Neuroradiol 20:207–211

    CAS  PubMed  Google Scholar 

  • Mueller SG, Weiner MW (2009) Selective effect of age, Apo e4, and Alzheimer’s disease on hippocampal subfields. Hippocampus 19:558–564. doi:10.1002/hipo.20614

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mueller SG, Stables L, Du AT, Schuff N, Truran D, Cashdollar N, Weiner MW (2007) Measurement of hippocampal subfields and age-related changes with high resolution MRI at 4T. Neurobiol Aging 28:719–726

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mueller SG, Chao LL, Berman B, Weiner MW (2011) Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4T. Neuroimage 56:851–857. doi:10.1016/j.neuroimage.2011.03.028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113

    Article  CAS  PubMed  Google Scholar 

  • Papiol S, Molina V, Desco M, Rosa A, Reig S, Gispert JD, Sanz J, Palomo T, Fañanás L (2005) Ventricular enlargement in schizophrenia is associated with a genetic polymorphism at the interleukin-1 receptor antagonist gene. Neuroimage 27:1002–1006

    Article  PubMed  Google Scholar 

  • Papiol S, Molina V, Desco M, Rosa A, Reig S, Sanz J, Palomo T, Fañanás L (2008) Gray matter deficits in bipolar disorder are associated with genetic variability at interleukin-1 beta gene (2q13). Genes Brain Behav 7:796–801. doi:10.1111/j.1601-183X.2008.00421.x

    Article  CAS  PubMed  Google Scholar 

  • Pedra JH, Cassel SL, Sutterwala FS (2009) Sensing pathogens and danger signals by the inflammasome. Curr Opin Immunol 21:10–16. doi:10.1016/j.coi.2009.01.006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pereira JB, Valls-Pedret C, Ros E, Palacios E, Falcón C, Bargalló N, Bartrés-Faz D, Wahlund LO, Westman E, Junque C (2014) Regional vulnerability of hippocampal subfields to aging measured by structural and diffusion MRI. Hippocampus 24:403–414. doi:10.1002/hipo.22234

    Article  PubMed  Google Scholar 

  • Petito CK, Pulsinelli WA (1984) Delayed neuronal recovery and neuronal death in rat hippocampus following severe cerebral ischemia: possible relationship to abnormalities in neuronal processes. J Cereb Blood Flow Metab 4:194–205

    Article  CAS  PubMed  Google Scholar 

  • Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ (2005) Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the subcommittee of Professional and Public Education of the American Heart Association Council on high blood pressure research. Hypertension 45:142–161

    Article  CAS  PubMed  Google Scholar 

  • Pievani M, Galluzzi S, Thompson PM, Rasser PE, Bonetti M, Frisoni GB (2011) APOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer’s disease. Neuroimage 55:909–919. doi:10.1016/j.neuroimage.2010.12.081

    Article  CAS  PubMed  Google Scholar 

  • Pulsinelli WA, Waldman S, Rawlinson D, Plum F (1982) Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. Neurology 32:1239–1246

    Article  CAS  PubMed  Google Scholar 

  • Qiu C, Zhang Y, Bronge L, Herlitz A, Aspelin P, Bäckman L, Fratiglioni L, Wahlund LO (2012) Medial temporal lobe is vulnerable to vascular risk factors in men: a population-based study. Eur J Neurol 19:876–883. doi:10.1111/j.1468-1331.2011.03645.x

    Article  CAS  PubMed  Google Scholar 

  • Qiu LR, Germann J, Spring S, Alm C, Vousden DA, Palmert MR, Lerch JP (2013) Hippocampal volumes differ across the mouse estrous cycle, can change within 24 hours, and associate with cognitive strategies. Neuroimage 83:593–598. doi:10.1016/j.neuroimage.2013.06.074

    Article  PubMed  Google Scholar 

  • Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Article  Google Scholar 

  • Rasgon NL, Kenna HA, Wroolie TE, Kelley R, Silverman D, Brooks J, Williams KE, Powers BN, Hallmayer J, Reiss A (2011) Insulin resistance and hippocampal volume in women at risk for Alzheimer’s disease. Neurobiol Aging 32:1942–1948. doi:10.1016/j.neurobiolaging.2009.12.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ravaglia G, Paola F, Maioli F, Martelli M, Montesi F, Bastagli L, Bianchin M, Chiappelli M, Tumini E, Bolondi L, Licastro F (2006) Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study. Exp Gerontol 41:85–92

    Article  CAS  PubMed  Google Scholar 

  • Raz N (2000) Aging of the brain and its impact on cognitive performance: Integration of structural and functional findings. In: Craik FIM, Salthouse TA (eds) Handbook of aging and cognition—II. Erlbaum, New Jersey, pp 1–90

    Google Scholar 

  • Raz N, Kennedy KM (2009) A systems approach to the aging brain: neuroanatomic changes, their modifiers, and cognitive correlates. In: Jagust W, D’Esposito M (eds) Imaging the aging brain. Oxford University Press, New York, pp 43–70

    Chapter  Google Scholar 

  • Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Dahle C, Gerstorf D, Acker JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15:1676–1689

    Article  PubMed  Google Scholar 

  • Raz N, Lindenberger U, Ghisletta P, Rodrigue KM, Kennedy KM, Acker JD (2008) Neuroanatomical correlates of fluid intelligence in healthy adults and persons with vascular risk factors. Cereb Cortex 18:718–726

    Article  PubMed Central  PubMed  Google Scholar 

  • Raz N, Yang Y, Dahle CL, Land S (2012) Volume of white matter hyperintensities in healthy adults: contribution of age, vascular risk factors, and inflammation-related genetic variants. Biochim Biophys Acta 1822:361–369. doi:10.1016/j.bbadis.2011.08.007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Reynolds E (2006) Vitamin B12, folic acid, and the nervous system. Lancet Neurol 5:949–960

    Article  CAS  PubMed  Google Scholar 

  • Richter-Schmidinger T, Alexopoulos P, Horn M, Maus S, Reichel M, Rhein C, Lewczuk P, Sidiropoulos C, Kneib T, Perneczky R, Doerfler A, Kornhuber J (2011) Influence of brain-derived neurotrophic-factor and apolipoprotein E genetic variants on hippocampal volume and memory performance in healthy young adults. J Neural Transm 118:249–257. doi:10.1007/s00702-010-0539-8

    Article  CAS  PubMed  Google Scholar 

  • Roses AD (1996) Apolipoprotein E and Alzheimer’s disease. A rapidly expanding field with medical and epidemiological consequences. Ann N Y Acad Sci 802:50–57

    Article  CAS  PubMed  Google Scholar 

  • Satizabal CL, Zhu YC, Mazoyer B, Dufouil C, Tzourio C (2012) Circulating IL-6 and CRP are associated with MRI findings in the elderly: the 3C-Dijon Study. Neurology 78:720–727. doi:10.1212/WNL.0b013e318248e50f

    Article  CAS  PubMed  Google Scholar 

  • Shing YL, Rodrigue KM, Kennedy KM, Fandakova Y, Bodammer N, Werkle-Bergner M, Lindenberger U, Raz N (2011) Hippocampal subfield volumes: age, vascular risk, and correlation with associative memory. Front Aging Neurosci 3:2. doi:10.3389/fnagi.2011.00002

    Article  PubMed Central  PubMed  Google Scholar 

  • Shrout PE, Fleiss JL (1979) Intraclass correlations: uses in assessing rater reliability. Psychol Bull 86:420–428

    Article  CAS  PubMed  Google Scholar 

  • Simi A, Tsakiri N, Wang P, Rothwell NJ (2007) Interleukin-1 and inflammatory neurodegeneration. Biochem Soc Trans 35:1122–1126

    Article  CAS  PubMed  Google Scholar 

  • Small SA, Schobel SA, Buxton RB, Witter MP, Barnes CA (2011) A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat Rev Neurosci 12:585–601. doi:10.1038/nrn3085

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155

    Article  PubMed  Google Scholar 

  • Sugawara T, Lewén A, Noshita N, Gasche Y, Chan PH (2002) Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. J Neurotrauma 19:85–98

    Article  PubMed  Google Scholar 

  • Sullivan EV, Marsh L, Mathalon DH, Lim KO, Pfefferbaum A (1995) Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus. Neurobiol Aging 16:591–606

    Article  CAS  PubMed  Google Scholar 

  • Suyama K (1992) Changes of neuronal transmission in the hippocampus after transient ischemia in spontaneously hypertensive rats and the protective effects of MK-801. Stroke 23:260–266

    Article  CAS  PubMed  Google Scholar 

  • Troyer AK, Murphy KJ, Anderson ND, Craik FI, Moscovitch M, Maione A, Gao F (2012) Associative recognition in mild cognitive impairment: Relationship to hippocampal volume and apolipoprotein E. Neuropsychologia 50:3721–3728. doi:10.1016/j.neuropsychologia.2012.10.018

    Article  PubMed  Google Scholar 

  • Tso AR, Merino JG, Warach S (2007) Interleukin-6 174G/C polymorphism and ischemic stroke: a systematic review. Stroke 38:3070–3075

    Article  CAS  PubMed  Google Scholar 

  • van Leemput K, Bakkour A, Benner T, Wiggins G, Wald LL, Augustinack J (2009) Automated segmentation of hippocampal subfields from ultra-high resolution in vivo MRI. Hippocampus 19:549–557

    Article  PubMed Central  PubMed  Google Scholar 

  • Vitkovic L, Konsman JP, Bockaert J, Dantzer R, Homburger V, Jacque C (2000) Cytokine signals propagate through the brain. Mol Psychiatry 5:604–615

    Article  CAS  PubMed  Google Scholar 

  • Williamson LL, Bilbo SD (2013) Chemokines and the hippocampus: a new perspective on hippocampal plasticity and vulnerability. Brain Behav Immun 30:186–194. doi:10.1016/j.bbi.2013.01.077

    Article  CAS  PubMed  Google Scholar 

  • Wills AK, Lawlor DA, Matthews FE, Sayer AA, Bakra E, Ben-Shlomo Y, Benzeval M, Brunner E, Cooper R, Kivimaki M, Kuh D, Muniz-Terrera G, Hardy R (2011) Life course trajectories of systolic blood pressure using longitudinal data from eight UK cohorts. PLoS Med 8:e1000440. doi:10.1371/journal.pmed.1000440

    Article  PubMed Central  PubMed  Google Scholar 

  • Witter MP, Amaral DG (1995) Hippocampal formation. In: Paxinos GT (ed) The rat nervous system, 2nd edn. Academic Press, California, pp 443–493

    Google Scholar 

  • Wolf OT, Dyakin V, Patel A, Vadasz C, de Leon MJ, McEwen BS, Bulloch K (2002) Volumetric structural magnetic resonance imaging (MRI) of the rat hippocampus following kainic acid (KA) treatment. Brain Res 934:87–96

    Article  CAS  PubMed  Google Scholar 

  • Yirmiya R, Goshen I (2011) Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 25:181–213. doi:10.1016/j.bbi.2010.10.015

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge their funding sponsor, the National Institutes of Health, grant number R37 AG-11230.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standards

The human study contained herein was approved by the Institutional Review Board and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants provided informed consent in accord with University Institutional Review Board guidelines.

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Authors and Affiliations

  1. Department of Psychology and Institute of Gerontology, Wayne State University, 87 E. Ferry St., 226 Knapp Building, Detroit, MI, 48202, USA

    Naftali Raz & Ana M. Daugherty

  2. Institute of Gerontology, Wayne State University, 87 E. Ferry St., 226 Knapp Building, Detroit, MI, 48202, USA

    Andrew R. Bender & Cheryl L. Dahle

  3. Department of Obstetrics and Gynecology, Wayne State University, 275 East Hancock, C.S. Mott Center, Detroit, MI, 48201, USA

    Susan Land

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  1. Naftali Raz
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  2. Ana M. Daugherty
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  3. Andrew R. Bender
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  4. Cheryl L. Dahle
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  5. Susan Land
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Correspondence to Naftali Raz.

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Raz, N., Daugherty, A.M., Bender, A.R. et al. Volume of the hippocampal subfields in healthy adults: differential associations with age and a pro-inflammatory genetic variant. Brain Struct Funct 220, 2663–2674 (2015). https://doi.org/10.1007/s00429-014-0817-6

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  • DOI: https://doi.org/10.1007/s00429-014-0817-6

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