TY - JOUR
T1 - Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging
AU - Vemuri, Prashanthi
AU - Lesnick, Timothy G.
AU - Przybelski, Scott A.
AU - Graff-Radford, Jonathan
AU - Reid, Robert I.
AU - Lowe, Val J.
AU - Zuk, Samantha M.
AU - Senjem, Matthew L.
AU - Schwarz, Christopher G.
AU - Gunter, Jeffrey L.
AU - Kantarci, Kejal
AU - Machulda, Mary M.
AU - Mielke, Michelle M.
AU - Petersen, Ronald C.
AU - Knopman, David S.
AU - Jack, Clifford R.
N1 - Publisher Copyright:
© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
PY - 2018/11
Y1 - 2018/11
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;84:713–724.
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;84:713–724.
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U2 - 10.1002/ana.25346
DO - 10.1002/ana.25346
M3 - Article
C2 - 30264411
AN - SCOPUS:85055490032
SN - 0364-5134
VL - 84
SP - 705
EP - 716
JO - Annals of neurology
JF - Annals of neurology
IS - 5
ER -