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Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Association between total-Tau and brain atrophy one year after first-ever stroke

Authors: Hege Ihle-Hansen, Guri Hagberg, Brynjar Fure, Bente Thommessen, Morten W. Fagerland, Anne R. Øksengård, Knut Engedal, Per Selnes

Published in: BMC Neurology | Issue 1/2017

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Abstract

Background

Although the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural MRI and pathological cerebrospinal fluid (CSF) concentrations of microtubule-associated protein tau (T-tau) and phosphorylated microtubule-associated protein tau indicate neurofibrillary degeneration. We aimed to explore the association between CSF T-tau and brain atrophy 1 year post-stroke.

Methods

We included 210 patients with first-ever ischemic stroke or transitory ischemic attack without pre-existing cognitive impairment. After 12 months, subjects underwent MRI, and CSF biomarkers were assessed. Using SIENAX (part of FSL), ventricular CSF volume and total brain volume were estimated and normalized for subject head size. The association between T-tau as explanatory variable and ventricular and total brain volume as outcome variables were studied using linear regression.

Results

One hundred eighty-two patients completed the follow-up. Forty-four had a lumbar puncture. Of these, 31 had their MRI with identical scan parameters. Mean age was 70.2 years (SD 11.7). Ventricular volume on MRI was significantly associated with age, but not with gender. In the multiple regression model, there was a significant association between T-tau and both ventricular (beta 0.44, 95% CI 376.3, 394.9, p = 0.021) and global brain volume (beta −0.50, 95% CI −565.9, −78.3, p = 0.011). There was no significant association between CSF T-tau 1 year post-stroke and baseline volumes.

Conclusion

T-tau measured 1 year post-stroke is associated with measures of brain atrophy. The findings indicate that acute stroke may enhance or trigger tau-linked neurodegeneration with loss of neurons.

Trial registration

Clinicaltrials.gov NCT00506818, July 23, 2007.
Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.
Literature
1.
go back to reference Breteler MM. Vascular involvement in cognitive decline and dementia. Epidemiologic evidence from the Rotterdam study and the Rotterdam scan study. Ann N Y Acad Sci. 2000;903:457–65.CrossRefPubMed Breteler MM. Vascular involvement in cognitive decline and dementia. Epidemiologic evidence from the Rotterdam study and the Rotterdam scan study. Ann N Y Acad Sci. 2000;903:457–65.CrossRefPubMed
2.
go back to reference Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348(13):1215–22.CrossRefPubMed Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348(13):1215–22.CrossRefPubMed
3.
4.
go back to reference Ostergaard L, Jespersen SN, Mouridsen K, Mikkelsen IK, Jonsdottir KY, Tietze A, et al. The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model. J Cereb Blood Flow Metab. 2013;33(5):635–48.CrossRefPubMedPubMedCentral Ostergaard L, Jespersen SN, Mouridsen K, Mikkelsen IK, Jonsdottir KY, Tietze A, et al. The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model. J Cereb Blood Flow Metab. 2013;33(5):635–48.CrossRefPubMedPubMedCentral
5.
go back to reference Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 2009;8(11):1006–18.CrossRefPubMed Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 2009;8(11):1006–18.CrossRefPubMed
6.
go back to reference Pendlebury ST. Dementia in patients hospitalized with stroke: rates, time course, and clinico-pathologic factors. Int J Stroke. 2012;7(7):570–81.CrossRefPubMed Pendlebury ST. Dementia in patients hospitalized with stroke: rates, time course, and clinico-pathologic factors. Int J Stroke. 2012;7(7):570–81.CrossRefPubMed
7.
go back to reference Tolppanen AM, Solomon A, Soininen H, Kivipelto M. Midlife vascular risk factors and Alzheimer's disease: evidence from epidemiological studies. J Alzheimers Dis. 2012;32(3):531–40.PubMed Tolppanen AM, Solomon A, Soininen H, Kivipelto M. Midlife vascular risk factors and Alzheimer's disease: evidence from epidemiological studies. J Alzheimers Dis. 2012;32(3):531–40.PubMed
8.
go back to reference Thiel A, Cechetto DF, Heiss WD, Hachinski V, Whitehead SN. Amyloid burden, neuroinflammation, and links to cognitive decline after ischemic stroke. Stroke. 2014;45(9):2825–9.CrossRefPubMed Thiel A, Cechetto DF, Heiss WD, Hachinski V, Whitehead SN. Amyloid burden, neuroinflammation, and links to cognitive decline after ischemic stroke. Stroke. 2014;45(9):2825–9.CrossRefPubMed
9.
go back to reference Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6(3):131–44.CrossRefPubMed Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6(3):131–44.CrossRefPubMed
10.
go back to reference Hesse C, Rosengren L, Vanmechelen E, Vanderstichele H, Jensen C, Davidsson P, et al. Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. J Alzheimers Dis. 2000;2(3–4):199–206.CrossRefPubMed Hesse C, Rosengren L, Vanmechelen E, Vanderstichele H, Jensen C, Davidsson P, et al. Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. J Alzheimers Dis. 2000;2(3–4):199–206.CrossRefPubMed
11.
go back to reference Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207–16.CrossRefPubMedPubMedCentral Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207–16.CrossRefPubMedPubMedCentral
12.
go back to reference Fein G, Di Sclafani V, Tanabe J, Cardenas V, Weiner MW, Jagust WJ, et al. Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology. 2000;55(11):1626–35.CrossRefPubMedPubMedCentral Fein G, Di Sclafani V, Tanabe J, Cardenas V, Weiner MW, Jagust WJ, et al. Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology. 2000;55(11):1626–35.CrossRefPubMedPubMedCentral
13.
go back to reference Lee JH, Kim SH, Kim GH, Seo SW, Park HK, Oh SJ, et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology. 2011;77(1):18–25.CrossRefPubMed Lee JH, Kim SH, Kim GH, Seo SW, Park HK, Oh SJ, et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology. 2011;77(1):18–25.CrossRefPubMed
14.
go back to reference Selnes P, Grambaite R, Rincon M, Bjornerud A, Gjerstad L, Hessen E, et al. Hippocampal complex atrophy in poststroke and mild cognitive impairment. J Cereb Blood Flow Metab. 2015;35(11):1729–37.CrossRefPubMedPubMedCentral Selnes P, Grambaite R, Rincon M, Bjornerud A, Gjerstad L, Hessen E, et al. Hippocampal complex atrophy in poststroke and mild cognitive impairment. J Cereb Blood Flow Metab. 2015;35(11):1729–37.CrossRefPubMedPubMedCentral
16.
go back to reference Selnes P, Blennow K, Zetterberg H, Grambaite R, Rosengren L, Johnsen L, et al. Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid. Cerebrospinal Fluid Res. 2010;7:10.CrossRefPubMedPubMedCentral Selnes P, Blennow K, Zetterberg H, Grambaite R, Rosengren L, Johnsen L, et al. Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid. Cerebrospinal Fluid Res. 2010;7:10.CrossRefPubMedPubMedCentral
17.
go back to reference Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, et al. Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci U S A. 2006;103(49):18727–32.CrossRefPubMedPubMedCentral Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, et al. Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci U S A. 2006;103(49):18727–32.CrossRefPubMedPubMedCentral
18.
go back to reference Kitagawa K, Matsumoto M, Niinobe M, Mikoshiba K, Hata R, Ueda H, et al. Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage--immunohistochemical investigation of dendritic damage. Neuroscience. 1989;31(2):401–11.CrossRefPubMed Kitagawa K, Matsumoto M, Niinobe M, Mikoshiba K, Hata R, Ueda H, et al. Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage--immunohistochemical investigation of dendritic damage. Neuroscience. 1989;31(2):401–11.CrossRefPubMed
19.
go back to reference Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68(3):409–27.CrossRefPubMedPubMedCentral Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68(3):409–27.CrossRefPubMedPubMedCentral
20.
go back to reference Shackelford DA, Nelson KE. Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit spinal cord. J Neurochem. 1996;66(1):286–95.CrossRefPubMed Shackelford DA, Nelson KE. Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit spinal cord. J Neurochem. 1996;66(1):286–95.CrossRefPubMed
21.
go back to reference Shackelford DA, Yeh RY. Dephosphorylation of tau during transient forebrain ischemia in the rat. Mol Chem Neuropathol. 1998;34(2–3):103–20.CrossRefPubMed Shackelford DA, Yeh RY. Dephosphorylation of tau during transient forebrain ischemia in the rat. Mol Chem Neuropathol. 1998;34(2–3):103–20.CrossRefPubMed
22.
go back to reference Burkhart KK, Beard DC, Lehman RA, Billingsley ML. Alterations in tau phosphorylation in rat and human neocortical brain slices following hypoxia and glucose deprivation. Exp Neurol. 1998;154(2):464–72.CrossRefPubMed Burkhart KK, Beard DC, Lehman RA, Billingsley ML. Alterations in tau phosphorylation in rat and human neocortical brain slices following hypoxia and glucose deprivation. Exp Neurol. 1998;154(2):464–72.CrossRefPubMed
23.
go back to reference Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol. 2013;698(1–3):6–18.CrossRefPubMed Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol. 2013;698(1–3):6–18.CrossRefPubMed
24.
go back to reference Mailliot C, Podevin-Dimster V, Rosenthal RE, Sergeant N, Delacourte A, Fiskum G, et al. Rapid tau protein dephosphorylation and differential rephosphorylation during cardiac arrest-induced cerebral ischemia and reperfusion. J Cereb Blood Flow Metab. 2000;20(3):543–9.CrossRefPubMed Mailliot C, Podevin-Dimster V, Rosenthal RE, Sergeant N, Delacourte A, Fiskum G, et al. Rapid tau protein dephosphorylation and differential rephosphorylation during cardiac arrest-induced cerebral ischemia and reperfusion. J Cereb Blood Flow Metab. 2000;20(3):543–9.CrossRefPubMed
25.
go back to reference Zhang Q, Gao T, Luo Y, Chen X, Gao G, Gao X, et al. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease. PLoS One. 2012;7(3):e33722.CrossRefPubMedPubMedCentral Zhang Q, Gao T, Luo Y, Chen X, Gao G, Gao X, et al. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease. PLoS One. 2012;7(3):e33722.CrossRefPubMedPubMedCentral
26.
go back to reference Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.CrossRefPubMed Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.CrossRefPubMed
27.
go back to reference Schaapsmeerders P, van Uden IW, Tuladhar AM, Maaijwee NA, van Dijk EJ, Rutten-Jacobs LC, et al. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults. Hum Brain Mapp. 2015;36(7):2432–42.CrossRefPubMed Schaapsmeerders P, van Uden IW, Tuladhar AM, Maaijwee NA, van Dijk EJ, Rutten-Jacobs LC, et al. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults. Hum Brain Mapp. 2015;36(7):2432–42.CrossRefPubMed
28.
go back to reference Ihle-Hansen H, Thommessen B, Fagerland MW, Oksengard AR, Wyller TB, Engedal K, Fure B: Multifactorial vascular risk factor intervention to prevent cognitive impairment after stroke and TIA: a 12-month randomized controlled trial. Int J Stroke. 2014;9:932-38. Ihle-Hansen H, Thommessen B, Fagerland MW, Oksengard AR, Wyller TB, Engedal K, Fure B: Multifactorial vascular risk factor intervention to prevent cognitive impairment after stroke and TIA: a 12-month randomized controlled trial. Int J Stroke. 2014;9:932-38.
29.
go back to reference Jorm AF, Jacomb PA. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med. 1989;19(4):1015–22.CrossRefPubMed Jorm AF, Jacomb PA. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med. 1989;19(4):1015–22.CrossRefPubMed
30.
go back to reference Goldstein LB, Bertels C, Davis JN. Interrater reliability of the NIH stroke scale. Arch Neurol. 1989;46(6):660–2.CrossRefPubMed Goldstein LB, Bertels C, Davis JN. Interrater reliability of the NIH stroke scale. Arch Neurol. 1989;46(6):660–2.CrossRefPubMed
31.
go back to reference Sulter G, Steen C, De KJ. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke. 1999;30(8):1538–41.CrossRefPubMed Sulter G, Steen C, De KJ. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke. 1999;30(8):1538–41.CrossRefPubMed
32.
go back to reference 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(3):189–98.CrossRefPubMed 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(3):189–98.CrossRefPubMed
33.
34.
go back to reference Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept mot Skills. 1958;8:271–6.CrossRef Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept mot Skills. 1958;8:271–6.CrossRef
35.
go back to reference Randolph C, Tierney MC, Mohr E, Chase TN. The repeatable battery for the assessment of neuropsychological status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998;20(3):310–9.CrossRefPubMed Randolph C, Tierney MC, Mohr E, Chase TN. The repeatable battery for the assessment of neuropsychological status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998;20(3):310–9.CrossRefPubMed
36.
go back to reference Adams H, Bendixen B, Kappelle L, Biller J, Love B, Gordon D. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke Treatment. Stroke. 1993;24:35–41.CrossRefPubMed Adams H, Bendixen B, Kappelle L, Biller J, Love B, Gordon D. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke Treatment. Stroke. 1993;24:35–41.CrossRefPubMed
37.
go back to reference Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337(8756):1521–6.CrossRefPubMed Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337(8756):1521–6.CrossRefPubMed
38.
go back to reference Smith SM, De Stefano N, Jenkinson M, Matthews PM. Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr. 2001;25(3):466–75.CrossRefPubMed Smith SM, De Stefano N, Jenkinson M, Matthews PM. Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr. 2001;25(3):466–75.CrossRefPubMed
39.
go back to reference Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Federico A, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17(1):479–89.CrossRefPubMed Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Federico A, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17(1):479–89.CrossRefPubMed
40.
go back to reference Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208–19.CrossRefPubMed Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208–19.CrossRefPubMed
42.
go back to reference Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5(2):143–56.CrossRefPubMed Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5(2):143–56.CrossRefPubMed
43.
go back to reference Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage. 2002;17(2):825–41.CrossRefPubMed Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage. 2002;17(2):825–41.CrossRefPubMed
44.
go back to reference Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging. 2001;20(1):45–57.CrossRefPubMed Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging. 2001;20(1):45–57.CrossRefPubMed
45.
go back to reference Ostergaard L, Aamand R, Gutierrez-Jimenez E, Ho YC, Blicher JU, Madsen SM, et al. The capillary dysfunction hypothesis of Alzheimer's disease. Neurobiol Aging. 2013;34(4):1018–31.CrossRefPubMed Ostergaard L, Aamand R, Gutierrez-Jimenez E, Ho YC, Blicher JU, Madsen SM, et al. The capillary dysfunction hypothesis of Alzheimer's disease. Neurobiol Aging. 2013;34(4):1018–31.CrossRefPubMed
Metadata
Title
Association between total-Tau and brain atrophy one year after first-ever stroke
Authors
Hege Ihle-Hansen
Guri Hagberg
Brynjar Fure
Bente Thommessen
Morten W. Fagerland
Anne R. Øksengård
Knut Engedal
Per Selnes
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0890-6

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