Brain Metabolites and Cognitive Function among Older Depressed and Healthy Individuals Using 2D MR Spectroscopy

Abstract

Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Twodimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.

Which pulse sequence is optimal for myo‐inositol detection at 3T?

“…While arguments may exist on why such approaches would offer better sensitivity than the n-quantum filters in NMR experiments (28), practical aspects of implementing such approaches in clinical scanners (such as relatively large minimum echo times, and a low resolution in the second dimension, to keep acquisition time manageable) have rendered the use of these techniques questionable for routine MRS acquisitions. The reduced repeatability of such measurements reported in vitro (mI CV's of ∼20% reported in Table 2 of (29)) and in vivo (30,31) (mI CV's in excess of 10% reported from data acquired with an SNR level of at least 4 times higher than the highest SNR considered in this report) have led the author to exclude such approaches from the current report. It is also questionable how efficient of a separation between Gly and mI is achievable with these acquisitions, while keeping the acquisition time manageable; overestimation of Gly by 160% and underestimation of mI by ∼20% have been reported in a brain phantom (29), indicating improper separation of the two metabolites.…”

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI‐cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies

“…Wyckoff and colleagues (2003) also reported increased myo-inositol concentrations in the left dorsolateral white matter of unmedicated late-life MDD patients. Moreover, a recent study correlated the increase in left dorsolateral prefrontal cortex myoinositol with increased cognitive function in healthy volunteers by not in late-life MDD patients (Elderkin- Thompson et al, 2004). In contrast, in a similar studies, no differences in frontal lobe myo-inositol concentrations were found between unmedicated MDD patients and healthy controls (Gruber et al, 2003a;Binesh et al, 2004).…”

Structural Neuroimaging of Geriatric Depression

“…Among nondepressed subjects, cognition positively correlated with Cho/Cr and mI/Cr and negatively correlated with phosphocholine/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation, whereas, depressed patients did not have consistent relationships between the metabolites. (89) Thus imaging studies have revealed both neuroanatomic as well as biochemical changes in the frontostriatal circuitry that may be associated with cognitive changes in depression.…”