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The impact of blood pressure on hippocampal glutamate and mnestic function

Journal of Human Hypertension volume 25, pages 256–261 (2011)Cite this article

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Abstract

Hypertension is associated with an increased risk of cognitive decline, which is generally regarded as a consequence of advanced cerebral atherosclerosis. Many hypertensive patients, however, suffer from cognitive decline long before they have any signs of cerebrovascular disease. Therefore, this study examines direct effects of blood pressure on neurotransmitter status in the hippocampus, a vulnerable cerebral structure relevant for memory consolidation. Absolute glutamate concentration and N-acetylaspartate (NAA) concentration as an alternative marker of neuronal integrity were determined in the hippocampus and the cerebral cortex (anterior cingulate cortex; ACC) by 3-T proton magnetic resonance spectroscopy in 16 probands without any history of cerebrovascular disease. Memory function was tested by the auditory verbal learning test (AVLT) and the rivermead behavioural memory test (RBMT). Arterial stiffness was assessed by augmentation index (AI). Mean arterial pressure showed a significant negative age-adjusted correlation to absolute glutamate concentrations in the hippocampus (R=−0.655, P=0.011), but not in the ACC. There was no significant correlation of mean arterial pressure and NAA in either hippocampus or ACC. AI did not affect hippocampal glutamate. Moreover, there was a significant negative correlation between mean arterial pressure and AVLT (r=−0.558, P=0.025) and RBMT score (r=−0.555, P=0.026). There is an inverse relation between blood pressure and the concentration of hippocampal glutamate. Glutamate is essential for long-term potentiation, the neurobiological correlate for memory formation in the hippocampus. Thus, hypertension-associated cognitive decline may not only be mediated by structural atherosclerotic wall changes, but also by functional changes in neurotransmission.

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References

  1. Elias MF, Wolf PA, D’Agostino RB, Cobb J, White LR . Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol 1993; 138: 353–364.

    Article  CAS  Google Scholar 

  2. Dufouil C, Chalmers J, Coskun O, Besancon V, Bousser MG, Guillon P et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation 2005; 112: 1644–1650.

    Article  Google Scholar 

  3. Tzourio C, Dufouil C, Ducimetiere P, Alperovitch A . Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of vascular aging. Neurology 1999; 53: 1948–1952.

    Article  CAS  Google Scholar 

  4. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000; 21: 49–55.

    Article  CAS  Google Scholar 

  5. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001; 322: 1447–1451.

    Article  CAS  PubMed  Google Scholar 

  6. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002; 324: 699–702.

    Article  CAS  PubMed  Google Scholar 

  7. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhager WH, Babarskiene MR et al. Prevention of dementia in randomised double-blind placebo-controlled systolic hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347–1351.

    Article  CAS  Google Scholar 

  8. Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic diseases in the Elderly Research Group. Neurology 2000; 54: S4–S9.

    Article  CAS  Google Scholar 

  9. Fratiglioni L, Launer LJ, Andersen K, Breteler MM, Copeland JR, Dartigues JF et al. Incidence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic diseases in the Elderly Research Group. Neurology 2000; 54: S10–S15.

    CAS  Google Scholar 

  10. Chui H . Vascular dementia, a new beginning: shifting focus from clinical phenotype to ischemic brain injury. Neurol Clin 2000; 18: 951–978.

    Article  CAS  Google Scholar 

  11. Qiu C, Winblad B, Fratiglioni L . The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005; 4: 487–499.

    Article  Google Scholar 

  12. Gallinat J, Strohle A, Lang UE, Bajbouj M, Kalus P, Montag C et al. Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety. Neuroimage 2005; 26: 123–131.

    Article  Google Scholar 

  13. Gallinat J, Schubert F, Bruhl R, Hellweg R, Klar AA, Kehrer C et al. Met carriers of BDNF Val66Met genotype show increased N-acetylaspartate concentration in the anterior cingulate cortex. Neuroimage 2010; 49: 767–771.

    Article  CAS  Google Scholar 

  14. Schubert F, Gallinat J, Seifert F, Rinneberg H . Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla. Neuroimage 2004; 21: 1762–1771.

    Article  Google Scholar 

  15. Elster C, Schubert F, Link A, Walzel M, Seifert F, Rinneberg H . Quantitative magnetic resonance spectroscopy: semi-parametric modeling and determination of uncertainties. Magn Reson Med 2005; 53: 1288–1296.

    Article  CAS  Google Scholar 

  16. Schubert F, Lahnor B, Seifert F, Rinneberg H . Effective transverse relaxation time of the C4 proton multiplet resonance of glutamate in tissue phantoms and human brain at 3 Tesla. Proc Int Soc Mag Reson Med 2004; 11: 1491.

    Google Scholar 

  17. Ashburner J, Friston K . Multimodal image coregistration and partitioning—a unified framework. Neuroimage 1997; 6: 209–217.

    Article  CAS  Google Scholar 

  18. Rey A . L’examen Clinique En Psychologie. Presses Universitaires de France: Paris, 1964.

    Google Scholar 

  19. Wilson B, Cockburn J, Baddeley A . The Rivermead Behavioural Memory Test. Thames Valley Tests Company: Bury St Edmunds, 1985.

    Google Scholar 

  20. McKenna PJ, Tamlyn D, Lund CE, Mortimer AM, Hammond S, Baddeley AD . Amnesic syndrome in schizophrenia. Psychol Med 1990; 20: 967–972.

    Article  CAS  Google Scholar 

  21. Westhoff TH, Schmidt S, Glander P, Liefeld L, Martini S, Offermann G et al. The impact of FTY720 (fingolimod) on vasodilatory function and arterial elasticity in renal transplant patients. Nephrol Dial Transplant 2007; 22: 2354–2358.

    Article  CAS  Google Scholar 

  22. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.

    Article  CAS  PubMed  Google Scholar 

  23. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25(6): 1105–1187.

    Article  CAS  Google Scholar 

  24. Lang UE, Hellweg R, Seifert F, Schubert F, Gallinat J . Correlation between serum brain-derived neurotrophic factor level and an in vivo marker of cortical integrity. Biol Psychiatry 2007; 62: 530–535.

    Article  CAS  Google Scholar 

  25. Simmons ML, Frondoza CG, Coyle JT . Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991; 45: 37–45.

    Article  CAS  Google Scholar 

  26. Nitkunan A, Charlton RA, Barrick TR, McIntyre DJ, Howe FA, Markus HS . Reduced N-acetylaspartate is consistent with axonal dysfunction in cerebral small vessel disease. NMR Biomed 2009; 22: 285–291.

    Article  CAS  Google Scholar 

  27. Ross B, Bluml S . Magnetic resonance spectroscopy of the human brain. Anat Rec 2001; 265: 54–84.

    Article  CAS  Google Scholar 

  28. Budson AE . Understanding memory dysfunction. Neurologist 2009; 15: 71–79.

    Article  Google Scholar 

  29. Billard JM . Ageing, hippocampal synaptic activity and magnesium. Magnes Res 2006; 19: 199–215.

    CAS  Google Scholar 

  30. Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E et al. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit. Nature 1995; 373: 151–155.

    Article  CAS  Google Scholar 

  31. Zhang DX, Levy WB . Ketamine blocks the induction of LTP at the lateral entorhinal cortex-dentate gyrus synapses. Brain Res 1992; 593: 124–127.

    Article  CAS  Google Scholar 

  32. Win-shwe TT, Hojo R, Mitsushima D, Nakajima D, Yamamoto S, Fujimaki H . Establishment of a mouse model to assess brain neurotransmitter level and learning performance simultaneously following toxic chemical exposure: using in vivo microdialysis and schedule-controlled operant behavior. J Uoeh 2009; 31: 1–11.

    Article  CAS  Google Scholar 

  33. Gallinat J, Kunz D, Senkowski D, Kienast T, Seifert F, Schubert F et al. Hippocampal glutamate concentration predicts cerebral theta oscillations during cognitive processing. Psychopharmacology (Berl) 2006; 187: 103–111.

    Article  CAS  Google Scholar 

  34. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199–214.

    Article  CAS  Google Scholar 

  35. Ghoneim MM, Hinrichs JV, Mewaldt SP, Petersen RC . Ketamine: behavioral effects of subanesthetic doses. J Clin Psychopharmacol 1985; 5: 70–77.

    Article  CAS  Google Scholar 

  36. Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005; 36: 2193–2197.

    Article  Google Scholar 

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Acknowledgements

JG has received research funding from the German Federal Ministry of Education and Research.

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Authors and Affiliations

  1. Department of Nephrology, Charité—Campus Benjamin Franklin, Berlin, Germany

    T H Westhoff, M Joppke & W Zidek

  2. Physikalisch-Technische Bundesanstalt (PTB), Abbestraße 2-12, Berlin, Germany

    F Schubert

  3. Department of Psychiatry and Psychotherapy, Charité—Campus Mitte, Berlin, Germany

    C Wirth, A A Klär & J Gallinat

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  1. T H Westhoff
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Correspondence to T H Westhoff.

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Westhoff, T., Schubert, F., Wirth, C. et al. The impact of blood pressure on hippocampal glutamate and mnestic function. J Hum Hypertens 25, 256–261 (2011). https://doi.org/10.1038/jhh.2010.51

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