1H-MRS metabolites and rate of β-amyloid accumulation on serial PET in clinically normal adults

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Abstract

OBJECTIVE: To assess whether noninvasive proton magnetic resonance spectroscopy (1H-MRS) tissue metabolite measurements at baseline can predict an increase in the rate of β-amyloid (Aβ) accumulation on serial PET in clinically normal (CN) older adults.

METHODS: Consecutive participants aged 60 years and older (n = 594) from the Mayo Clinic Study of Aging who were CN at baseline and who underwent 1H-MRS from the posterior cingulate voxel and longitudinal 11C-Pittsburgh compound B (PiB)-PET were included. The rate of Aβ accumulation by serial cortical PiB standardized uptake value ratios was estimated as a function of baseline 1H-MRS metabolite ratios and time using mixed-effect models adjusted for age, sex, and APOE ε4. Effect of APOE ε4 on the relationship between baseline MRS and an increased rate of Aβ accumulation was also assessed.

RESULTS: Among all participants, a higher myo-inositol (mI)/creatine (p = 0.011) and a lower N-acetylaspartate/mI (p = 0.006) at baseline were associated with an increased Aβ accumulation over time after adjusting for age, sex, and APOE ε4. APOE ε4 did not modify the association of baseline 1H-MRS metabolite ratios and rate of Aβ accumulation. However, APOE ε4 carriers accumulated Aβ faster than noncarriers regardless of the baseline Aβ load (p = 0.001).

CONCLUSION: Among CN older adults, early metabolic alterations on 1H-MRS and APOE ε4 status are independently associated with an increased rate of Aβ accumulation. Our findings could have important implications for early diagnosis and identification of individuals for secondary prevention trials, because an increased rate of Aβ accumulation in CN older adults may confer a higher risk for cognitive decline and mild cognitive impairment.

Original languageEnglish (US)
Pages (from-to)1391-1399
Number of pages9
JournalNeurology
Volume89
Issue number13
DOIs
StatePublished - Sep 26 2017

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Amyloid
Inositol
Creatine
Gyrus Cinguli
Secondary Prevention
Proton Magnetic Resonance Spectroscopy
Early Diagnosis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{c57175b45fc14fd499766e067bb18ff2,
title = "1H-MRS metabolites and rate of β-amyloid accumulation on serial PET in clinically normal adults",
abstract = "OBJECTIVE: To assess whether noninvasive proton magnetic resonance spectroscopy (1H-MRS) tissue metabolite measurements at baseline can predict an increase in the rate of β-amyloid (Aβ) accumulation on serial PET in clinically normal (CN) older adults.METHODS: Consecutive participants aged 60 years and older (n = 594) from the Mayo Clinic Study of Aging who were CN at baseline and who underwent 1H-MRS from the posterior cingulate voxel and longitudinal 11C-Pittsburgh compound B (PiB)-PET were included. The rate of Aβ accumulation by serial cortical PiB standardized uptake value ratios was estimated as a function of baseline 1H-MRS metabolite ratios and time using mixed-effect models adjusted for age, sex, and APOE ε4. Effect of APOE ε4 on the relationship between baseline MRS and an increased rate of Aβ accumulation was also assessed.RESULTS: Among all participants, a higher myo-inositol (mI)/creatine (p = 0.011) and a lower N-acetylaspartate/mI (p = 0.006) at baseline were associated with an increased Aβ accumulation over time after adjusting for age, sex, and APOE ε4. APOE ε4 did not modify the association of baseline 1H-MRS metabolite ratios and rate of Aβ accumulation. However, APOE ε4 carriers accumulated Aβ faster than noncarriers regardless of the baseline Aβ load (p = 0.001).CONCLUSION: Among CN older adults, early metabolic alterations on 1H-MRS and APOE ε4 status are independently associated with an increased rate of Aβ accumulation. Our findings could have important implications for early diagnosis and identification of individuals for secondary prevention trials, because an increased rate of Aβ accumulation in CN older adults may confer a higher risk for cognitive decline and mild cognitive impairment.",
author = "Zuzana Nedelska and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Christopher Schwarz and Val Lowe and Machulda, {Mary Margaret} and Kremers, {Walter K} and Mielke, {Michelle M} and Roberts, {Rosebud O} and Boeve, {Bradley F} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Kantarci, {Kejal M}",
year = "2017",
month = "9",
day = "26",
doi = "10.1212/WNL.0000000000004421",
language = "English (US)",
volume = "89",
pages = "1391--1399",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "13",

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TY - JOUR

T1 - 1H-MRS metabolites and rate of β-amyloid accumulation on serial PET in clinically normal adults

AU - Nedelska, Zuzana

AU - Przybelski, Scott A.

AU - Lesnick, Timothy G.

AU - Schwarz, Christopher

AU - Lowe, Val

AU - Machulda, Mary Margaret

AU - Kremers, Walter K

AU - Mielke, Michelle M

AU - Roberts, Rosebud O

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Kantarci, Kejal M

PY - 2017/9/26

Y1 - 2017/9/26

N2 - OBJECTIVE: To assess whether noninvasive proton magnetic resonance spectroscopy (1H-MRS) tissue metabolite measurements at baseline can predict an increase in the rate of β-amyloid (Aβ) accumulation on serial PET in clinically normal (CN) older adults.METHODS: Consecutive participants aged 60 years and older (n = 594) from the Mayo Clinic Study of Aging who were CN at baseline and who underwent 1H-MRS from the posterior cingulate voxel and longitudinal 11C-Pittsburgh compound B (PiB)-PET were included. The rate of Aβ accumulation by serial cortical PiB standardized uptake value ratios was estimated as a function of baseline 1H-MRS metabolite ratios and time using mixed-effect models adjusted for age, sex, and APOE ε4. Effect of APOE ε4 on the relationship between baseline MRS and an increased rate of Aβ accumulation was also assessed.RESULTS: Among all participants, a higher myo-inositol (mI)/creatine (p = 0.011) and a lower N-acetylaspartate/mI (p = 0.006) at baseline were associated with an increased Aβ accumulation over time after adjusting for age, sex, and APOE ε4. APOE ε4 did not modify the association of baseline 1H-MRS metabolite ratios and rate of Aβ accumulation. However, APOE ε4 carriers accumulated Aβ faster than noncarriers regardless of the baseline Aβ load (p = 0.001).CONCLUSION: Among CN older adults, early metabolic alterations on 1H-MRS and APOE ε4 status are independently associated with an increased rate of Aβ accumulation. Our findings could have important implications for early diagnosis and identification of individuals for secondary prevention trials, because an increased rate of Aβ accumulation in CN older adults may confer a higher risk for cognitive decline and mild cognitive impairment.

AB - OBJECTIVE: To assess whether noninvasive proton magnetic resonance spectroscopy (1H-MRS) tissue metabolite measurements at baseline can predict an increase in the rate of β-amyloid (Aβ) accumulation on serial PET in clinically normal (CN) older adults.METHODS: Consecutive participants aged 60 years and older (n = 594) from the Mayo Clinic Study of Aging who were CN at baseline and who underwent 1H-MRS from the posterior cingulate voxel and longitudinal 11C-Pittsburgh compound B (PiB)-PET were included. The rate of Aβ accumulation by serial cortical PiB standardized uptake value ratios was estimated as a function of baseline 1H-MRS metabolite ratios and time using mixed-effect models adjusted for age, sex, and APOE ε4. Effect of APOE ε4 on the relationship between baseline MRS and an increased rate of Aβ accumulation was also assessed.RESULTS: Among all participants, a higher myo-inositol (mI)/creatine (p = 0.011) and a lower N-acetylaspartate/mI (p = 0.006) at baseline were associated with an increased Aβ accumulation over time after adjusting for age, sex, and APOE ε4. APOE ε4 did not modify the association of baseline 1H-MRS metabolite ratios and rate of Aβ accumulation. However, APOE ε4 carriers accumulated Aβ faster than noncarriers regardless of the baseline Aβ load (p = 0.001).CONCLUSION: Among CN older adults, early metabolic alterations on 1H-MRS and APOE ε4 status are independently associated with an increased rate of Aβ accumulation. Our findings could have important implications for early diagnosis and identification of individuals for secondary prevention trials, because an increased rate of Aβ accumulation in CN older adults may confer a higher risk for cognitive decline and mild cognitive impairment.

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U2 - 10.1212/WNL.0000000000004421

DO - 10.1212/WNL.0000000000004421

M3 - Article

C2 - 28842444

AN - SCOPUS:85030610246

VL - 89

SP - 1391

EP - 1399

JO - Neurology

JF - Neurology

SN - 0028-3878

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