• Olga Voevodskaya, Konstantinos Poulakis, Pia Sundgren, Danielle van Westen, Sebastian Palmqvist, Lars-Olof Wahlund, Erik Stomrud, Oskar Hansson, Eric Westman, and Swedish BioFINDER Study Group.
• From the Division of Clinical Geriatrics (O.V., K.P., L.-O.W., E.W.), Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm; Department of Diagnostic Radiology (P.S., D.v.W.), Lund University; Imaging and Function (D.v.W.), Skåne University Health Care, Lund; Clinical Memory Research Unit (S.P., E.S., O.H.), Department of Clinical Sciences, Malmö, Lund University; Memory Clinic (E.S., O.H.), Skåne University Hospital, Malmö, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. olga.voevodskaya@ki.se.
• Neurology. 2019 Jan 29; 92 (5): e395-e405.

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 Aβ+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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