Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

Prashanthi Vemuri; Timothy G. Lesnick; Scott A. Przybelski; David S. Knopman; Val J. Lowe; Jonathan Graff-Radford; Rosebud O. Roberts; Michelle M. Mielke; Mary M. Machulda; Ronald C. Petersen; Clifford R. Jack

doi:10.1002/ana.25071

Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

Prashanthi Vemuri, Timothy G. Lesnick, Scott A. Przybelski, David S. Knopman, Val J. Lowe, Jonathan Graff-Radford, Rosebud O. Roberts, Michelle M. Mielke, Mary M. Machulda, Ronald C. Petersen, Clifford R. Jack

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

72 Scopus citations

Abstract

Objective: To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. Methods: We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC⁻) versus CMC > 0 (CMC⁺) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. Results: CMC⁺ participants had significantly greater neurodegeneration than CMC⁻ participants but did not differ by amyloid or ERC-tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC-tau. Interpretation: Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706–718.

Original language	English (US)
Pages (from-to)	706-718
Number of pages	13
Journal	Annals of neurology
Volume	82
Issue number	5
DOIs	https://doi.org/10.1002/ana.25071
State	Published - Nov 2017

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.25071

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title = "Age, vascular health, and Alzheimer disease biomarkers in an elderly sample",

abstract = "Objective: To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. Methods: We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC−) versus CMC > 0 (CMC+) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. Results: CMC+ participants had significantly greater neurodegeneration than CMC− participants but did not differ by amyloid or ERC-tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC-tau. Interpretation: Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706–718.",

author = "Prashanthi Vemuri and Lesnick, {Timothy G.} and Przybelski, {Scott A.} and Knopman, {David S.} and Lowe, {Val J.} and Jonathan Graff-Radford and Roberts, {Rosebud O.} and Mielke, {Michelle M.} and Machulda, {Mary M.} and Petersen, {Ronald C.} and Jack, {Clifford R.}",

note = "Publisher Copyright: {\textcopyright} 2017 American Neurological Association",

year = "2017",

month = nov,

doi = "10.1002/ana.25071",

language = "English (US)",

volume = "82",

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T1 - Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

AU - Vemuri, Prashanthi

AU - Lesnick, Timothy G.

AU - Przybelski, Scott A.

AU - Knopman, David S.

AU - Lowe, Val J.

AU - Graff-Radford, Jonathan

AU - Roberts, Rosebud O.

AU - Mielke, Michelle M.

AU - Machulda, Mary M.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

PY - 2017/11

Y1 - 2017/11

N2 - Objective: To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. Methods: We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC−) versus CMC > 0 (CMC+) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. Results: CMC+ participants had significantly greater neurodegeneration than CMC− participants but did not differ by amyloid or ERC-tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC-tau. Interpretation: Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706–718.

AB - Objective: To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. Methods: We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC−) versus CMC > 0 (CMC+) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. Results: CMC+ participants had significantly greater neurodegeneration than CMC− participants but did not differ by amyloid or ERC-tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC-tau. Interpretation: Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706–718.

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Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

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