Magnetic Resonance Spectroscopy Insights Into Late-Life Depression: Advances in Brain Metabolic Profiling

Background: Late-life depression (LLD) is a primary depression with onset age greater than 60 years old. The typical clinical manifestations of patients include low mood and impaired cognitive function, which may be related to their neurobiochemical changes. Magnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and other neurometabolites in patients with LLD, clarifying their neurobiochemical characteristics.Objective: This systematic review examined the existing evidence regarding MRS in LLD, emphasizing the connection between brain metabolites and clinical symptoms, including depression and cognitive deficits.Methods: A systematic search was conducted across PubMed, Embase, Web of Science, Cochrane, and gray literature to identify studies relevant to this systematic review. The included studies summarized the alterations in metabolites within the brain regions associated with LLD and explored the correlation between these metabolites and clinical symptoms, aiming to elucidate the neurobiochemical features of LLD.Results: In patients with LLD, the N-acetylaspartate (NAA) level was significantly reduced in the frontal cortex and was positively correlated with the severity of depressive symptoms. Furthermore, lower NAA/creatine (Cr) levels in the hippocampus were positively linked to reduced cognitive functions. The NAA level was also reduced, while myo-Inositol (mI) and the glutathione (GSH) to Cr ratio were increased in the cingulate cortex. Specifically, a higher GSH/Cr ratio in the anterior cingulate cortex correlated positively with depressive symptom severity. Conversely, the GSH/Cr ratio in the left lingual gyrus negatively correlated with language acquisition proficiency. Similarly, depressive symptom improvement was inversely related to a decrease in the glutamate (Glu)/total Cr (tCr) ratio in the posterior cingulate cortex (PCC) after antidepressant treatment. In contrast, the mI level showed a significant rise in the left temporal lobe and basal ganglia, and a negative correlation was observed between the mI/tCr ratio in the basal ganglia and overall cognitive performance. The choline to Cr ratio was also elevated in both the whole brain and the basal ganglia. Additionally, the levels of potential of hydrogen and potential of magnesium (pMg) were increased in gray matter. Conversely, white matter showed reduced nucleoside triphosphates, beta-nucleoside triphosphates (beta-NTP), and pMg. Moreover, beta-NTP and inorganic phosphate (Pi) were significantly associated with executive function in white matter.Conclusion: LLD is associated with neurobiochemical alterations in the frontal lobe, cingulate gyrus, and other areas of the brain, which are strongly linked to depressive symptoms and cognitive impairment. In contrast, the neurobiochemical changes observed in the hippocampus and parietal lobe are distinctive features in cognitive disorders, indicating that the underlying mechanisms of cognitive impairment in these two conditions differ.