Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study

Hadassa M. Jochemsen; Raoul P Kloppenborg; Lisette C P G M De Groot; Ellen Kampman; Willem P T M Mali; Yolanda van der Graaf; Mirjam I Geerlings

doi:10.1016/j.jalz.2011.11.008

Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study

Hadassa M. Jochemsen, Raoul P Kloppenborg, Lisette C P G M De Groot, Ellen Kampman, Willem P T M Mali, Yolanda van der Graaf, Mirjam I Geerlings,

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

Abstract

BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age.

METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added.

RESULTS: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively).

CONCLUSION: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons.

Original language	English
Pages (from-to)	302-309
Number of pages	8
Journal	Alzheimer's & Dementia
Volume	9
Issue number	3
DOIs	https://doi.org/10.1016/j.jalz.2011.11.008
Publication status	Published - 2013

Keywords

Aged
Aging
Atherosclerosis
Atrophy
Biomarkers
Cerebral Infarction
Cerebral Ventricles
Cognition Disorders
Disease Progression
Executive Function
Female
Homocysteine
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Middle Aged
Neuropsychological Tests
Prospective Studies
Risk Factors
Journal Article
Research Support, Non-U.S. Gov't

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10.1016/j.jalz.2011.11.008

http://www.ncbi.nlm.nih.gov/pubmed/22863909

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Jochemsen, H. M., Kloppenborg, R. P., De Groot, L. C. P. G. M., Kampman, E., Mali, W. P. T. M., van der Graaf, Y., Geerlings, M. I. (2013). Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study. Alzheimer's & Dementia, 9(3), 302-309. https://doi.org/10.1016/j.jalz.2011.11.008

@article{a044f79a5118482e98c46c73b51c0036,

title = "Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study",

abstract = "BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age.METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added.RESULTS: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively).CONCLUSION: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons.",

keywords = "Aged, Aging, Atherosclerosis, Atrophy, Biomarkers, Cerebral Infarction, Cerebral Ventricles, Cognition Disorders, Disease Progression, Executive Function, Female, Homocysteine, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Risk Factors, Journal Article, Research Support, Non-U.S. Gov't",

author = "Jochemsen, {Hadassa M.} and Kloppenborg, {Raoul P} and {De Groot}, {Lisette C P G M} and Ellen Kampman and Mali, {Willem P T M} and {van der Graaf}, Yolanda and Geerlings, {Mirjam I} and FLJ Visseren and LJ Kappelle and DE Grobbee and PA Doevendans and GEHM Rutten and FL Moll",

year = "2013",

doi = "10.1016/j.jalz.2011.11.008",

language = "English",

volume = "9",

pages = "302--309",

journal = "Alzheimer's & Dementia",

issn = "1552-5260",

publisher = "John Wiley & Sons Inc.",

number = "3",

}

Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study. / Jochemsen, Hadassa M.; Kloppenborg, Raoul P; De Groot, Lisette C P G M et al.
In: Alzheimer's & Dementia, Vol. 9, No. 3, 2013, p. 302-309.

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

TY - JOUR

T1 - Homocysteine, progression of ventricular enlargement, and cognitive decline

T2 - the Second Manifestations of ARTerial disease-Magnetic Resonance study

AU - Jochemsen, Hadassa M.

AU - Kloppenborg, Raoul P

AU - De Groot, Lisette C P G M

AU - Kampman, Ellen

AU - Mali, Willem P T M

AU - van der Graaf, Yolanda

AU - Geerlings, Mirjam I

AU - Visseren, FLJ

AU - Kappelle, LJ

AU - Grobbee, DE

AU - Doevendans, PA

AU - Rutten, GEHM

AU - Moll, FL

PY - 2013

Y1 - 2013

N2 - BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age.METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added.RESULTS: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively).CONCLUSION: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons.

AB - BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age.METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added.RESULTS: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively).CONCLUSION: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons.

KW - Aged

KW - Aging

KW - Atherosclerosis

KW - Atrophy

KW - Biomarkers

KW - Cerebral Infarction

KW - Cerebral Ventricles

KW - Cognition Disorders

KW - Disease Progression

KW - Executive Function

KW - Female

KW - Homocysteine

KW - Humans

KW - Longitudinal Studies

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Neuropsychological Tests

KW - Prospective Studies

KW - Risk Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jalz.2011.11.008

DO - 10.1016/j.jalz.2011.11.008

M3 - Article

C2 - 22863909

SN - 1552-5260

VL - 9

SP - 302

EP - 309

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 3

ER -

Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study

Abstract

Keywords

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