Abstract
Our objective was to investigate the influence of hypertension on N-acetylaspartate (NAA) and choline (Cho) ratios in brain tissues in a community-dwelling elderly population. Brain flexibility was also evaluated with regard to the same metabolite ratios. Proton magnetic resonance spectroscopy (MRS) and the Trail Making Test (TMT) were performed in 80 subjects (75.7±4 years old) from the Three-City Study. Fifty-eight participants had hypertension. The NAA/creatine (Cr) and Cho/Cr ratios were obtained in the insular cortex, the thalami and the deep periventricular white matter. In addition, the B-A score of the TMT was evaluated. Uniand multi-variate analyses were performed in order to examine the relationships among these data. In the insula and the thalami of the hypertensive group, NAA/Cr ratios were significantly lower (1.39±0.23 and 1.52±0.23, respectively; p=0.01) than those in the normotensive control goup (1.52±0.25 and 1.70±0.19, respectively; p<0.0001), whereas no such reduction was observed in the periventricular white matter of older hypertensive brains. Moreover, the NAA or Cho ratios were significantly correlated with the TMT B-A scores at the level of the thalami, insula and periventricular white matter. These statistical results were confirmed by the multivariate analysis. In an elderly population, hypertension leads to a reduction in NAA/Cr ratios in the insula and the thalami, possibly due to a decrease in blood flow through small perforating and cortical arteries. The TMT B-A test appears to be relevant not only for the frontal areas but also for more remote areas such as the thalami, the insula and the deep periventricular white matter.
Similar content being viewed by others
Article PDF
References
Firbank MJ, Wiseman RM, Burton EJ, Saxby BK, O'Brien JT, Ford GA : Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure. J Neurol 2007; 254: 713–721.
Kawamura J, Meyer JS, Terayama Y, Weathers S : Leukoaraiosis correlates with cerebral hypoperfusion in vascular dementia. Stroke 1991; 22: 609–614.
Beason-Held LL, Moghekar A, Zonderman AB, Kraut MA, Resnick SM : Longitudinal changes in cerebral blood flow in the older hypertensive brain. Stroke 2007; 38: 1766–1773.
Fujishima M, Ibayashi S, Fujii K, Mori S : Cerebral blood flow and brain function in hypertension. Hypertens Res 1995; 18: 111–117.
Mentis MJ, Salerno J, Horwitz B, et al: Reduction of functional neuronal connectivity in long-term treated hypertension. Stroke 1994; 25: 601–607.
Raz N, Rodrigue KM : Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 2006; 30: 730–748.
Walker PM, Ben Salem D, Lalande A, Giroud M, Brunotte F : Time course of NAA T2 and ADC(w) in ischaemic stroke patients: 1H MRS imaging and diffusion-weighted MRI. J Neurol Sci 2004; 220: 23–28.
Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM : N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 2007; 81: 89–131.
Ross AJ, Sachdev PS, Wen W, Brodaty H : Longitudinal changes during aging using proton magnetic resonance spectroscopy. J Gerontol A Biol Sci Med Sci 2006; 61: 291–298.
3C Study Group: Vascular factors and risk of dementia: design of the Three-City Study and baseline characteristics of the study population. Neuroepidemiology 2003; 22: 316–325.
Guenot M, Isnard J, Sindou M : Surgical anatomy of the insula. Adv Tech Stand Neurosurg 2004; 29: 265–288.
Goldstein IB, Bartzokis G, Hance DB, Shapiro D : Relationship between blood pressure and subcortical lesions in healthy elderly people. Stroke 1998; 29: 765–772.
Sander D, Klingelhöfer J : Changes of circadian blood pressure patterns after hemodynamic and thromboembolic brain infarction. Stroke 1994; 25: 1730–1737.
Folstein MF, Folstein SE, McHugh PR : “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.
Reitan RM : Validity of the trail-making test as an indication of organic brain damage. Percept Mot Skills 1958; 8: 271–276.
Perianez JA, Rios-Lago M, Rodriguez-Sanchez JM, et al: Trail Making Test in traumatic brain injury, schizophrenia, and normal ageing: sample comparisons and normative data. Arch Clin Neuropsychol 2007; 22: 433–447.
Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E : Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci 1996; 17: 305–309.
Mickey RM, Greenland S : The impact of confounder selection criteria on effect estimation. Am J Epidemiol 1989; 129: 125–137.
Twisk JWR ( ed): Applied Longitudinal Data Analysis for Epidemiology: A Practical Guide, 1st ed. Cambridge, Cambridge University Press, 2003.
Khan U, Porteous L, Hassan A, Markus HS : Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 2007; 78: 702–706.
Norrving B : Long-term prognosis after lacunar infarction. Lancet Neurol 2003; 2: 238–245.
Thal DR, Ghebremedhin E, Orantes M, Wiestler OD : Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 2003; 62: 1287–1301.
Ohmine T, Miwa Y, Yao H, et al: Association between arterial stiffness and cerebral white matter lesions in community-dwelling elderly subjects. Hypertens Res 2008; 31: 75–81.
Inzitari M, Pozzi C, Rinaldi LA, Masotti G, Marchionni N, Di Bari M : Cognitive and functional impairment in hypertensive brain microangiopathy. J Neurol Sci 2007; 257: 166–173.
Pugh KG, Lipsitz LA : The microvascular frontal-subcortical syndrome of aging. Neurobiol Aging 2002; 23: 421–431.
Cook IA, Leuchter AF, Morgan ML, et al: Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects. Arch Neurol 2002; 59: 1612–1620.
Sultzer DL, Mahler ME, Cummings JL, Van Gorp WG, Hinkin CH, Brown C : Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings. Arch Neurol 1995; 52: 773–780.
Miller SP, Li LM, Cendes F, et al: Medial temporal lobe neuronal damage in temporal and extratemporal lesional epilepsy. Neurology 2000; 54: 1465–1470.
Rango M, Spagnoli D, Tomei G, Bamonti F, Scarlato G, Zetta L : Central nervous system trans-synaptic effects of acute axonal injury: a 1H magnetic resonance spectroscopy study. Magn Reson Med 1995; 33: 595–600.
Uzan M, Albayram S, Dashti SG, Aydin S, Hanci M, Kuday C : Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury. J Neurol Neurosurg Psychiatry 2003; 74: 33–38.
Walker PM, Ben Salem D, Giroud M, Brunotte F : Is NAA reduction in normal contralateral cerebral tissue in stroke patients dependent on underlying risk factors? J Neurol Neurosurg Psychiatry 2006; 77: 596–600.
Gianaros PJ, Greer PJ, Ryan CM, Jennings JR : Higher blood perssure [predicts lower regional grey matter volume: consequences on short-term information processing. Neuroimage 2006; 31: 754–765.
Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO : In vivo spectroscopic quantification of the Nacetyl moiety, creatine, and choline from large volumes brain gray and white matter: effects of normal aging. Magn Reson Med 1999; 41: 276–284.
Charlton RA, McIntyre DJ, Howe FA, Morris RG, Markus HS : The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study. Brain Res 2007; 1164: 108–116.
Soury S, Mazaux JM, Lambert J, et al: The neurobehavioral rating scale-revised: assessment of concurrent validity. Ann Readapt Med Phys 2005; 48: 61–70.
Zakzanis KK, Mraz R, Graham SJ : An fMRI study of the Trail Making Test. Neuropsychologia 2005; 43: 1878–1886.
Marshall GA, Hendrickson R, Kaufer DI, Ivanco LS, Bohnen NI : Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly. Int J Geriatr Psychiatry 2006; 21: 32–35.
O'Sullivan M, Barrick TR, Morris RG, Clark CA, Markus HS : Damage within a network of white matter regions underlies executive dysfunction in CADASIL. Neurology 2005; 65: 1584–1590.
Hashimoto R, Meguro K, Lee E, Kasai M, Ishii H, Yamaguchi S : Effect of age and education on the Trail Making Test and determination of normative data for Japanese elderly people: the Tajiri Project. Psychiatry Clin Neurosci 2006; 60: 422–428.
Hester RL, Kinsella GJ, Ong B, McGregor J : Demographic influences on baseline and derived scores from the trail making test in healthy older Australian adults. Clin Neuropsychol 2005; 19: 45–54.
Sijens PE, den Heijer T D Origgi et al: Brain changes with aging: MR spectroscopy at supraventricular plane shows differences between women and men. Radiology 2003; 226: 889–896.
Svennerholm L, Boström K, Jungbjer B : Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes. Acta Neuropathol 1997; 94: 345–352.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Salem, D., Walker, P., Bejot, Y. et al. N-Acetylaspartate/Creatine and Choline/Creatine Ratios in the Thalami, Insular Cortex and White Matter as Markers of Hypertension and Cognitive Impairment in the Elderly. Hypertens Res 31, 1851–1857 (2008). https://doi.org/10.1291/hypres.31.1851
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.31.1851