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

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Brain myoinositol as a potential marker of amyloid-related pathology : A longitudinal study. / Voevodskaya, Olga; Poulakis, Konstantinos; Sundgren, Pia; Westen, Danielle Van; Palmqvist, Sebastian; Wahlund, Lars Olof; Stomrud, Erik; Hansson, Oskar; Westman, Eric.

I: Neurology, Vol. 92, Nr. 5, 29.01.2019, s. E395-E405.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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TY - JOUR

T1 - Brain myoinositol as a potential marker of amyloid-related pathology

T2 - Neurology

AU - Voevodskaya, Olga

AU - Poulakis, Konstantinos

AU - Sundgren, Pia

AU - Westen, Danielle Van

AU - Palmqvist, Sebastian

AU - Wahlund, Lars Olof

AU - Stomrud, Erik

AU - Hansson, Oskar

AU - Westman, Eric

PY - 2019/1/29

Y1 - 2019/1/29

N2 - 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.

AB - 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.

U2 - 10.1212/WNL.0000000000006852

DO - 10.1212/WNL.0000000000006852

M3 - Article

VL - 92

SP - E395-E405

JO - Neurology

JF - Neurology

SN - 1526-632X

IS - 5

ER -