Advanced

Brain myoinositol as a potential marker of amyloid-related pathology : A longitudinal study

Voevodskaya, Olga; Poulakis, Konstantinos; Sundgren, Pia LU ; Westen, Danielle Van LU ; Palmqvist, Sebastian LU ; Wahlund, Lars Olof; Stomrud, Erik LU ; Hansson, Oskar LU and Westman, Eric (2019) In Neurology 92(5). p.395-405
Abstract

ObjectiveTo investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.MethodsIn this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline β-amyloid (Aβ), and between MRS and the longitudinal Mini-Mental State... (More)

ObjectiveTo investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.MethodsIn this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline β-amyloid (Aβ), and between MRS and the longitudinal Mini-Mental State Examination, accounting for APOE, age, and sex.ResultsWhile baseline MRS metabolites were similar in Aβ positive (Aβ+) and negative (Aβ-) individuals, in the Aβ+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for N-acetylaspartate (NAA)/mI. In the Aβ- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment Aβ+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y (p = 0.07) for mI/Cr and -3.55%/y (p < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that Aβ+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than Aβ+ individuals with high baseline NAA/mI.ConclusionWe demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of Aβ-related processes over time. In addition, we show that in A7beta;+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
92
issue
5
pages
395 - 405
publisher
American Academy of Neurology
external identifiers
  • scopus:85065535775
ISSN
0028-3878
DOI
10.1212/WNL.0000000000006852
language
English
LU publication?
yes
id
577aaf2e-c307-4e50-b196-175099ccf2f3
date added to LUP
2019-05-21 21:35:02
date last changed
2019-07-16 04:09:36
@article{577aaf2e-c307-4e50-b196-175099ccf2f3,
  abstract     = {<p>ObjectiveTo investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.MethodsIn this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline β-amyloid (Aβ), and between MRS and the longitudinal Mini-Mental State Examination, accounting for APOE, age, and sex.ResultsWhile baseline MRS metabolites were similar in Aβ positive (Aβ+) and negative (Aβ-) individuals, in the Aβ+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for N-acetylaspartate (NAA)/mI. In the Aβ- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment Aβ+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y (p = 0.07) for mI/Cr and -3.55%/y (p &lt; 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that Aβ+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than Aβ+ individuals with high baseline NAA/mI.ConclusionWe demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of Aβ-related processes over time. In addition, we show that in A7beta;+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.</p>},
  author       = {Voevodskaya, Olga and Poulakis, Konstantinos and Sundgren, Pia and Westen, Danielle Van and Palmqvist, Sebastian and Wahlund, Lars Olof and Stomrud, Erik and Hansson, Oskar and Westman, Eric},
  issn         = {0028-3878},
  language     = {eng},
  month        = {01},
  number       = {5},
  pages        = {395--405},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Brain myoinositol as a potential marker of amyloid-related pathology : A longitudinal study},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000006852},
  volume       = {92},
  year         = {2019},
}