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

• Published in: Neurology Vol. 92; no. 5; pp. e395 - e405
• Main Authors: Voevodskaya, Olga, Poulakis, Konstantinos, Sundgren, Pia, van Westen, Danielle, Palmqvist, Sebastian, Wahlund, Lars-Olof, Stomrud, Erik, Hansson, Oskar, Westman, Eric
• Format: Journal Article
• Language: English
• Published: United States American Academy of Neurology 29-01-2019; Lippincott Williams & Wilkins
• Subjects: 1993; Aged; alzheimers-disease; Amyloid beta-Peptides - metabolism; apoe genotype; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; atrophy rates; Biomarkers - metabolism; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; cerebrospinal-fluid; Clinical Medicine; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Creatine - metabolism; Cross-Sectional Studies; Diagnostic Screening Programs; Disease Progression; Female; h-1 mrs; Humans; inositol; Inositol - metabolism; Klinisk medicin; Longitudinal Studies; magnetic resonance in medicine; magnetic-resonance-spectroscopy; Male; Medical and Health Sciences; Medicin och hälsovetenskap; n-acetylaspartate; Neurologi; Neurology; Neurosciences; Neurosciences & Neurology; Neurovetenskaper; ovencher sw; p672; posterior cingulate cortex; Proton Magnetic Resonance Spectroscopy; spectroscopy; v30
• ISSN: 0028-3878; 1526-632X; 1526-632X
• DOI: 10.1212/WNL.0000000000006852

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.