Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition

Lauren E. Salminen; Peter R. Schofield; Kerrie D. Pierce; Yi Zhao; Xi Luo; Youdan Wang; David H. Laidlaw; Ryan P. Cabeen; Thomas E. Conturo; David F. Tate; Erbil Akbudak; Elizabeth M. Lane; Jodi M. Heaps; Jacob D. Bolzenius; Laurie M. Baker; Lee M. Cagle; Robert H. Paul

doi:10.1016/j.bbr.2015.08.028

Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition

Lauren E. Salminen, Peter R. Schofield, Kerrie D. Pierce, Yi Zhao, Xi Luo, Youdan Wang, David H. Laidlaw, Ryan P. Cabeen, Thomas E. Conturo, David F. Tate, Erbil Akbudak, Elizabeth M. Lane, Jodi M. Heaps, Jacob D. Bolzenius, Laurie M. Baker, Lee M. Cagle, Robert H. Paul

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n= 27, ThrThr n= 27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.

Original language	English
Pages (from-to)	85-93
Number of pages	9
Journal	Behavioural Brain Research
Volume	296
DOIs	https://doi.org/10.1016/j.bbr.2015.08.028
State	Published - Jan 1 2016

Keywords

AGT
Cognition
M235T
M268T
Rs699
White matter

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Salminen, L. E., Schofield, P. R., Pierce, K. D., Zhao, Y., Luo, X., Wang, Y., Laidlaw, D. H., Cabeen, R. P., Conturo, T. E., Tate, D. F., Akbudak, E., Lane, E. M., Heaps, J. M., Bolzenius, J. D., Baker, L. M., Cagle, L. M., & Paul, R. H. (2016). Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition. Behavioural Brain Research, 296, 85-93. https://doi.org/10.1016/j.bbr.2015.08.028

@article{80e382f094b74d64b9e01d1efa713a8c,

title = "Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition",

abstract = "The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n= 27, ThrThr n= 27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.",

keywords = "AGT, Cognition, M235T, M268T, Rs699, White matter",

author = "Salminen, {Lauren E.} and Schofield, {Peter R.} and Pierce, {Kerrie D.} and Yi Zhao and Xi Luo and Youdan Wang and Laidlaw, {David H.} and Cabeen, {Ryan P.} and Conturo, {Thomas E.} and Tate, {David F.} and Erbil Akbudak and Lane, {Elizabeth M.} and Heaps, {Jodi M.} and Bolzenius, {Jacob D.} and Baker, {Laurie M.} and Cagle, {Lee M.} and Paul, {Robert H.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier B.V.",

year = "2016",

month = jan,

day = "1",

doi = "10.1016/j.bbr.2015.08.028",

language = "English",

volume = "296",

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Salminen, LE, Schofield, PR, Pierce, KD, Zhao, Y, Luo, X, Wang, Y, Laidlaw, DH, Cabeen, RP, Conturo, TE, Tate, DF, Akbudak, E, Lane, EM, Heaps, JM, Bolzenius, JD, Baker, LM, Cagle, LM & Paul, RH 2016, 'Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition', Behavioural Brain Research, vol. 296, pp. 85-93. https://doi.org/10.1016/j.bbr.2015.08.028

TY - JOUR

T1 - Neuromarkers of the common angiotensinogen polymorphism in healthy older adults

T2 - A comprehensive assessment of white matter integrity and cognition

AU - Salminen, Lauren E.

AU - Schofield, Peter R.

AU - Pierce, Kerrie D.

AU - Zhao, Yi

AU - Luo, Xi

AU - Wang, Youdan

AU - Laidlaw, David H.

AU - Cabeen, Ryan P.

AU - Conturo, Thomas E.

AU - Tate, David F.

AU - Akbudak, Erbil

AU - Lane, Elizabeth M.

AU - Heaps, Jodi M.

AU - Bolzenius, Jacob D.

AU - Baker, Laurie M.

AU - Cagle, Lee M.

AU - Paul, Robert H.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n= 27, ThrThr n= 27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.

AB - The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n= 27, ThrThr n= 27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.

KW - AGT

KW - Cognition

KW - M235T

KW - M268T

KW - Rs699

KW - White matter

UR - http://www.scopus.com/inward/record.url?scp=84941299793&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2015.08.028

DO - 10.1016/j.bbr.2015.08.028

M3 - Article

C2 - 26318936

AN - SCOPUS:84941299793

SN - 0166-4328

VL - 296

SP - 85

EP - 93

JO - Behavioural Brain Research

JF - Behavioural Brain Research

ER -

Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition

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Keywords

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