WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES

Geert Jan Biessels; Josephine Barnes; Carole H. Sudre; Hugh Pemberton; Cassidy M. Fiford; Owen T. Carmichael; Frederik Barkhof; Phoebe Walsh; M. Jorge Cardoso

doi:10.1016/j.jalz.2017.07.686

WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES

Geert Jan Biessels, Josephine Barnes, Carole H. Sudre, Hugh Pemberton, Cassidy M. Fiford, Owen T. Carmichael, Frederik Barkhof, Phoebe Walsh, M. Jorge Cardoso

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

Abstract

Background: Hippocampal volume change is an important diagnostic and disease-tracking biomarker in Alzheimer's disease (AD). As a proxy for global cerebral vascular disease (CVD), white matter hyperintensities (WMH) have been found to be predictive of hippocampal atrophy rates in controls and late mild cognitive impairment (LMCI). In this preliminary work we extend this to early MCI (EMCI) and assess whether WMH has predictive value over other CVD markers: lacunes and microbleeds (CMB). Methods:Data were from the Alzheimer's Disease Neuroimaging Initiative (Go and 2). We measured hippocampal atrophy rates using automated techniques (Similarity and Truth Estimation for Propagated Segmentations -STEPS, and symmetric Boundary Shift Integral -BSI) over a 12 month interval. WMH were measured on baseline images using a novel automated algorithm (Bayesian Model Selection -BaMoS). We counted CMBs and lacunes manually at baseline. For CMBs, results were categorised into 0, 1, 2-4 and >4 CMBs. Linear regression analyses were used to assess whether each CVD marker was associated with subsequent hippocampal change. For CMBs and lacunes, the reference groups against which those who had CMBs and lacunes were compared, were those with none. Separate models were fitted for each CVD marker and diagnostic group. Further models were fitted with all CVD markers as predictors. Other covariates included gender and intracranial volume (TIV). Results: Log2WMH was predictive of hippocampal atrophy rates in controls, EMCI and LMCI (see table). An overall test showed CMB category was predictive of hippocampal atrophy rates in controls. We found no evidence for a relationship of lacunes with hippocampal atrophy rates. Log2WMH was independently predictive of hippocampal atrophy rates in controls and LMCI, and at trend level in EMCI. Having 1 vs. 0 CMB was independently predictive of hippocampal rates in controls and AD. Conclusions: We found that CVD markers predict hippocampal atrophy in all diagnostic groups: WMH predicted atrophy in controls through to LMCI and CMB numbers predicted hippocampal tissue loss in controls and AD. The fact that many of these findings were independent of one another suggests that different aspects of vascular disease may contribute to disease progression.

Original language	English
Pages (from-to)	P1547-P1548
Journal	Alzheimer's & Dementia
Volume	13
Issue number	7
DOIs	https://doi.org/10.1016/j.jalz.2017.07.686
Publication status	Published - 20 Oct 2017

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Biessels, G. J., Barnes, J., Sudre, C. H., Pemberton, H., Fiford, C. M., Carmichael, O. T., Barkhof, F., Walsh, P., & Cardoso, M. J. (2017). WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES. Alzheimer's & Dementia, 13(7), P1547-P1548. https://doi.org/10.1016/j.jalz.2017.07.686

@article{85ce28623bf247d7822e487d44888129,

title = "WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES",

abstract = "Background: Hippocampal volume change is an important diagnostic and disease-tracking biomarker in Alzheimer's disease (AD). As a proxy for global cerebral vascular disease (CVD), white matter hyperintensities (WMH) have been found to be predictive of hippocampal atrophy rates in controls and late mild cognitive impairment (LMCI). In this preliminary work we extend this to early MCI (EMCI) and assess whether WMH has predictive value over other CVD markers: lacunes and microbleeds (CMB). Methods:Data were from the Alzheimer's Disease Neuroimaging Initiative (Go and 2). We measured hippocampal atrophy rates using automated techniques (Similarity and Truth Estimation for Propagated Segmentations -STEPS, and symmetric Boundary Shift Integral -BSI) over a 12 month interval. WMH were measured on baseline images using a novel automated algorithm (Bayesian Model Selection -BaMoS). We counted CMBs and lacunes manually at baseline. For CMBs, results were categorised into 0, 1, 2-4 and >4 CMBs. Linear regression analyses were used to assess whether each CVD marker was associated with subsequent hippocampal change. For CMBs and lacunes, the reference groups against which those who had CMBs and lacunes were compared, were those with none. Separate models were fitted for each CVD marker and diagnostic group. Further models were fitted with all CVD markers as predictors. Other covariates included gender and intracranial volume (TIV). Results: Log2WMH was predictive of hippocampal atrophy rates in controls, EMCI and LMCI (see table). An overall test showed CMB category was predictive of hippocampal atrophy rates in controls. We found no evidence for a relationship of lacunes with hippocampal atrophy rates. Log2WMH was independently predictive of hippocampal atrophy rates in controls and LMCI, and at trend level in EMCI. Having 1 vs. 0 CMB was independently predictive of hippocampal rates in controls and AD. Conclusions: We found that CVD markers predict hippocampal atrophy in all diagnostic groups: WMH predicted atrophy in controls through to LMCI and CMB numbers predicted hippocampal tissue loss in controls and AD. The fact that many of these findings were independent of one another suggests that different aspects of vascular disease may contribute to disease progression.",

author = "Biessels, {Geert Jan} and Josephine Barnes and Sudre, {Carole H.} and Hugh Pemberton and Fiford, {Cassidy M.} and Carmichael, {Owen T.} and Frederik Barkhof and Phoebe Walsh and Cardoso, {M. Jorge}",

year = "2017",

month = oct,

day = "20",

doi = "10.1016/j.jalz.2017.07.686",

language = "English",

volume = "13",

pages = "P1547--P1548",

journal = "Alzheimer's & Dementia",

issn = "1552-5260",

number = "7",

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Biessels, GJ, Barnes, J , Sudre, CH, Pemberton, H, Fiford, CM, Carmichael, OT, Barkhof, F, Walsh, P & Cardoso, MJ 2017, 'WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES', Alzheimer's & Dementia, vol. 13, no. 7, pp. P1547-P1548. https://doi.org/10.1016/j.jalz.2017.07.686

TY - JOUR

T1 - WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES

AU - Biessels, Geert Jan

AU - Barnes, Josephine

AU - Sudre, Carole H.

AU - Pemberton, Hugh

AU - Fiford, Cassidy M.

AU - Carmichael, Owen T.

AU - Barkhof, Frederik

AU - Walsh, Phoebe

AU - Cardoso, M. Jorge

PY - 2017/10/20

Y1 - 2017/10/20

N2 - Background: Hippocampal volume change is an important diagnostic and disease-tracking biomarker in Alzheimer's disease (AD). As a proxy for global cerebral vascular disease (CVD), white matter hyperintensities (WMH) have been found to be predictive of hippocampal atrophy rates in controls and late mild cognitive impairment (LMCI). In this preliminary work we extend this to early MCI (EMCI) and assess whether WMH has predictive value over other CVD markers: lacunes and microbleeds (CMB). Methods:Data were from the Alzheimer's Disease Neuroimaging Initiative (Go and 2). We measured hippocampal atrophy rates using automated techniques (Similarity and Truth Estimation for Propagated Segmentations -STEPS, and symmetric Boundary Shift Integral -BSI) over a 12 month interval. WMH were measured on baseline images using a novel automated algorithm (Bayesian Model Selection -BaMoS). We counted CMBs and lacunes manually at baseline. For CMBs, results were categorised into 0, 1, 2-4 and >4 CMBs. Linear regression analyses were used to assess whether each CVD marker was associated with subsequent hippocampal change. For CMBs and lacunes, the reference groups against which those who had CMBs and lacunes were compared, were those with none. Separate models were fitted for each CVD marker and diagnostic group. Further models were fitted with all CVD markers as predictors. Other covariates included gender and intracranial volume (TIV). Results: Log2WMH was predictive of hippocampal atrophy rates in controls, EMCI and LMCI (see table). An overall test showed CMB category was predictive of hippocampal atrophy rates in controls. We found no evidence for a relationship of lacunes with hippocampal atrophy rates. Log2WMH was independently predictive of hippocampal atrophy rates in controls and LMCI, and at trend level in EMCI. Having 1 vs. 0 CMB was independently predictive of hippocampal rates in controls and AD. Conclusions: We found that CVD markers predict hippocampal atrophy in all diagnostic groups: WMH predicted atrophy in controls through to LMCI and CMB numbers predicted hippocampal tissue loss in controls and AD. The fact that many of these findings were independent of one another suggests that different aspects of vascular disease may contribute to disease progression.

AB - Background: Hippocampal volume change is an important diagnostic and disease-tracking biomarker in Alzheimer's disease (AD). As a proxy for global cerebral vascular disease (CVD), white matter hyperintensities (WMH) have been found to be predictive of hippocampal atrophy rates in controls and late mild cognitive impairment (LMCI). In this preliminary work we extend this to early MCI (EMCI) and assess whether WMH has predictive value over other CVD markers: lacunes and microbleeds (CMB). Methods:Data were from the Alzheimer's Disease Neuroimaging Initiative (Go and 2). We measured hippocampal atrophy rates using automated techniques (Similarity and Truth Estimation for Propagated Segmentations -STEPS, and symmetric Boundary Shift Integral -BSI) over a 12 month interval. WMH were measured on baseline images using a novel automated algorithm (Bayesian Model Selection -BaMoS). We counted CMBs and lacunes manually at baseline. For CMBs, results were categorised into 0, 1, 2-4 and >4 CMBs. Linear regression analyses were used to assess whether each CVD marker was associated with subsequent hippocampal change. For CMBs and lacunes, the reference groups against which those who had CMBs and lacunes were compared, were those with none. Separate models were fitted for each CVD marker and diagnostic group. Further models were fitted with all CVD markers as predictors. Other covariates included gender and intracranial volume (TIV). Results: Log2WMH was predictive of hippocampal atrophy rates in controls, EMCI and LMCI (see table). An overall test showed CMB category was predictive of hippocampal atrophy rates in controls. We found no evidence for a relationship of lacunes with hippocampal atrophy rates. Log2WMH was independently predictive of hippocampal atrophy rates in controls and LMCI, and at trend level in EMCI. Having 1 vs. 0 CMB was independently predictive of hippocampal rates in controls and AD. Conclusions: We found that CVD markers predict hippocampal atrophy in all diagnostic groups: WMH predicted atrophy in controls through to LMCI and CMB numbers predicted hippocampal tissue loss in controls and AD. The fact that many of these findings were independent of one another suggests that different aspects of vascular disease may contribute to disease progression.

UR - http://www.mendeley.com/research/white-matter-hyperintensities-associated-hippocampal-atrophy-rates-after-adjusting-other-vascular-ma

U2 - 10.1016/j.jalz.2017.07.686

DO - 10.1016/j.jalz.2017.07.686

M3 - Article

SN - 1552-5260

VL - 13

SP - P1547-P1548

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 7

ER -

WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH HIPPOCAMPAL ATROPHY RATES AFTER ADJUSTING FOR OTHER VASCULAR MARKERS IN PREDEMENTIA DISEASE STAGES

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