Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging

Prashanthi D Vemuri, Timothy G. Lesnick, Scott A. Przybelski, Jonathan Graff-Radford, Robert I. Reid, Val Lowe, Samantha M. Zuk, Matthew L. Senjem, Christopher Schwarz, Jeffrey L. Gunter, Kejal M Kantarci, Mary Margaret Machulda, Michelle M Mielke, Ronald Carl Petersen, David S Knopman, Clifford R Jr. Jack

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Recent availability of amyloid and tau positron emission tomography (PET) has provided us with a unique opportunity to measure the association of systemic vascular health with brain health after accounting for the impact of Alzheimer disease (AD) pathologies. We wanted to quantify early cerebrovascular health–related magnetic resonance imaging brain measures (structure, perfusion, microstructural integrity) and evaluate their utility as a biomarker for cerebrovascular health. Methods: We used 2 independent samples (discovery, n = 390; validation, n = 1,035) of individuals, aged ≥ 60 years, along the cognitive continuum with imaging from the population-based sample of Mayo Clinic Study of Aging. We ascertained vascular health by summing up recently existing cardiovascular and metabolic conditions (CMC) from health care records (hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke). Using multiple regression models, we quantified associations between CMC and brain health after accounting for age, sex, education/occupation, and AD burden (from amyloid and tau PET). Results: Systemic vascular health was associated with medial temporal lobe thinning, widespread cerebral hypoperfusion, and loss of microstructural integrity in several white matter tracts including the corpus callosum and fornix. Further investigations suggested that microstructural integrity of the genu of the corpus callosum was suitable for assessing prodromal cerebrovascular health, had similar distributions in the discovery and independent validation datasets, and predicted cognitive performance above and beyond amyloid deposition. Interpretation: Systemic vascular health has significant impact on brain structure and function. Quantifying prodromal cerebrovascular health–related brain measures that are independent of AD pathology–related changes has great utility for cognitive aging. Ann Neurol 2018; 1–12.

Original languageEnglish (US)
JournalAnnals of Neurology
DOIs
StateAccepted/In press - Jan 1 2018

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Biomarkers
Magnetic Resonance Imaging
Health
Blood Vessels
Amyloid
Brain
Alzheimer Disease
Corpus Callosum
Positron-Emission Tomography
Sex Education
Cognitive Aging
Temporal Lobe
Hyperlipidemias
Occupations
Cardiac Arrhythmias
Coronary Artery Disease
Diabetes Mellitus
Heart Failure
Perfusion
Stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

@article{0036ddd38fbd4e8c81160c7cbee1e234,
title = "Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging",
abstract = "Objective: Recent availability of amyloid and tau positron emission tomography (PET) has provided us with a unique opportunity to measure the association of systemic vascular health with brain health after accounting for the impact of Alzheimer disease (AD) pathologies. We wanted to quantify early cerebrovascular health–related magnetic resonance imaging brain measures (structure, perfusion, microstructural integrity) and evaluate their utility as a biomarker for cerebrovascular health. Methods: We used 2 independent samples (discovery, n = 390; validation, n = 1,035) of individuals, aged ≥ 60 years, along the cognitive continuum with imaging from the population-based sample of Mayo Clinic Study of Aging. We ascertained vascular health by summing up recently existing cardiovascular and metabolic conditions (CMC) from health care records (hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke). Using multiple regression models, we quantified associations between CMC and brain health after accounting for age, sex, education/occupation, and AD burden (from amyloid and tau PET). Results: Systemic vascular health was associated with medial temporal lobe thinning, widespread cerebral hypoperfusion, and loss of microstructural integrity in several white matter tracts including the corpus callosum and fornix. Further investigations suggested that microstructural integrity of the genu of the corpus callosum was suitable for assessing prodromal cerebrovascular health, had similar distributions in the discovery and independent validation datasets, and predicted cognitive performance above and beyond amyloid deposition. Interpretation: Systemic vascular health has significant impact on brain structure and function. Quantifying prodromal cerebrovascular health–related brain measures that are independent of AD pathology–related changes has great utility for cognitive aging. Ann Neurol 2018; 1–12.",
author = "Vemuri, {Prashanthi D} and Lesnick, {Timothy G.} and Przybelski, {Scott A.} and Jonathan Graff-Radford and Reid, {Robert I.} and Val Lowe and Zuk, {Samantha M.} and Senjem, {Matthew L.} and Christopher Schwarz and Gunter, {Jeffrey L.} and Kantarci, {Kejal M} and Machulda, {Mary Margaret} and Mielke, {Michelle M} and Petersen, {Ronald Carl} and Knopman, {David S} and Jack, {Clifford R Jr.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/ana.25346",
language = "English (US)",
journal = "Annals of Neurology",
issn = "0364-5134",
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TY - JOUR

T1 - Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging

AU - Vemuri, Prashanthi D

AU - Lesnick, Timothy G.

AU - Przybelski, Scott A.

AU - Graff-Radford, Jonathan

AU - Reid, Robert I.

AU - Lowe, Val

AU - Zuk, Samantha M.

AU - Senjem, Matthew L.

AU - Schwarz, Christopher

AU - Gunter, Jeffrey L.

AU - Kantarci, Kejal M

AU - Machulda, Mary Margaret

AU - Mielke, Michelle M

AU - Petersen, Ronald Carl

AU - Knopman, David S

AU - Jack, Clifford R Jr.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: Recent availability of amyloid and tau positron emission tomography (PET) has provided us with a unique opportunity to measure the association of systemic vascular health with brain health after accounting for the impact of Alzheimer disease (AD) pathologies. We wanted to quantify early cerebrovascular health–related magnetic resonance imaging brain measures (structure, perfusion, microstructural integrity) and evaluate their utility as a biomarker for cerebrovascular health. Methods: We used 2 independent samples (discovery, n = 390; validation, n = 1,035) of individuals, aged ≥ 60 years, along the cognitive continuum with imaging from the population-based sample of Mayo Clinic Study of Aging. We ascertained vascular health by summing up recently existing cardiovascular and metabolic conditions (CMC) from health care records (hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke). Using multiple regression models, we quantified associations between CMC and brain health after accounting for age, sex, education/occupation, and AD burden (from amyloid and tau PET). Results: Systemic vascular health was associated with medial temporal lobe thinning, widespread cerebral hypoperfusion, and loss of microstructural integrity in several white matter tracts including the corpus callosum and fornix. Further investigations suggested that microstructural integrity of the genu of the corpus callosum was suitable for assessing prodromal cerebrovascular health, had similar distributions in the discovery and independent validation datasets, and predicted cognitive performance above and beyond amyloid deposition. Interpretation: Systemic vascular health has significant impact on brain structure and function. Quantifying prodromal cerebrovascular health–related brain measures that are independent of AD pathology–related changes has great utility for cognitive aging. Ann Neurol 2018; 1–12.

AB - Objective: Recent availability of amyloid and tau positron emission tomography (PET) has provided us with a unique opportunity to measure the association of systemic vascular health with brain health after accounting for the impact of Alzheimer disease (AD) pathologies. We wanted to quantify early cerebrovascular health–related magnetic resonance imaging brain measures (structure, perfusion, microstructural integrity) and evaluate their utility as a biomarker for cerebrovascular health. Methods: We used 2 independent samples (discovery, n = 390; validation, n = 1,035) of individuals, aged ≥ 60 years, along the cognitive continuum with imaging from the population-based sample of Mayo Clinic Study of Aging. We ascertained vascular health by summing up recently existing cardiovascular and metabolic conditions (CMC) from health care records (hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke). Using multiple regression models, we quantified associations between CMC and brain health after accounting for age, sex, education/occupation, and AD burden (from amyloid and tau PET). Results: Systemic vascular health was associated with medial temporal lobe thinning, widespread cerebral hypoperfusion, and loss of microstructural integrity in several white matter tracts including the corpus callosum and fornix. Further investigations suggested that microstructural integrity of the genu of the corpus callosum was suitable for assessing prodromal cerebrovascular health, had similar distributions in the discovery and independent validation datasets, and predicted cognitive performance above and beyond amyloid deposition. Interpretation: Systemic vascular health has significant impact on brain structure and function. Quantifying prodromal cerebrovascular health–related brain measures that are independent of AD pathology–related changes has great utility for cognitive aging. Ann Neurol 2018; 1–12.

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U2 - 10.1002/ana.25346

DO - 10.1002/ana.25346

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JO - Annals of Neurology

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SN - 0364-5134

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