3T hippocampal glutamate-glutamine complex reflects verbal memory decline in aging

Abstract

The hippocampus is a critical site for alterations that are responsible for age-related changes in memory. Here, we present a relatively novel approach of examining the relationship between memory performance and Glutamate-Glutamine levels using short echo time magnetic resonance spectroscopy (MRS). Specifically, we investigated the relationship between Glx (a composite of glutamate and glutamine) levels in the hippocampus, performance on a word recall task and resting state functional connectivity (RSFC). While there was no overall difference in Glx intensity between young and aging adults, we identified a positive correlation between delayed word-list recall and Glx, bilaterally in older adults, but not in young adults. Collapsed across age, we also discovered a negative relationship between Glx intensity and RSFC between the anterior hippocampus and regions in the subcallosal gyrus, replicating a recent finding by Wagner et al., (2016). These findings demonstrate the possibly utility of Glx in identifying age-related changes in the brain and behavior and provide encouragement that MRS can be useful in predicting age-related decline before any physical abnormalities are present.

Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal learning performance in the marmoset

“…In a recent functional MRS study, an increase in medial PFC Glx concentration was found when participants were engaged in a task of visual imagery, relative to a control condition [20], suggesting greater Glu/Gln cycling or increased synaptic glutamate release in response to task demands. Other studies found that Glx predicted performance on a verbal memory task in both young men [4] and older adults [5]. Our study extends these results for the first time in an NHP, by showing an association between PFC Glx and cognitive flexibility.…”

“…For example, NAA in cortical tissues has been found to correlate with selective aspects of cognitive performance in healthy populations [3]. Glx concentration in the hippocampus has also been shown to predict verbal memory performance in healthy adult males [4] and delayed word list recall in older adults [5]. However, Patel et al [3] caution that such approaches reveal brain/cognition associations that are typically small to moderate, and subject to a number of methodological biases.…”

Modulation on Glutamic Pathway of Frontal-Striatum-Thalamus by rs11146020 and rs3813296 Gene Polymorphism in First-Episode Negative Schizophrenia

“…As suggested in previous studies, it is also closely associated with the degeneration of the brain in schizophrenia patients (Zhang et al, 2012(Zhang et al, , 2014Cetin-Karayumak et al, 2019). Further, recent research mentioned that words and visuospatial memory information are conveyed across aforesaid regions via the excitatory projections of glutamatergic pyramidal neurons (Hoftman et al, 2017;Nikolova et al, 2017). More importantly, the current results are especially helpful for reminding clinical researchers to pay attention to the first-episode negative schizophrenia patients with the TT genotype.…”

Glutamine + glutamate level predicts the magnitude of microstructural organization in the gray matter in the healthy elderly

“…Thus, previous MRS studies showed that a decreased Glx level can be observed in neurodegenerative conditions, such as aging (Goryawala et al, 2016;Grachev et al, 2001), mild cognitive impairment and Alzheimer's disease (Antuono et al, 2001;Huang et al, 2016;Riese et al, 2015), in several GM regions including mPFC and PCC, which implies neuronal dysfunction and loss in these GM regions. Consistently, cognitive performance or cognitive symptoms have been reported to positively correlate with Glx levels in elderly people (Zahr et al, 2008) and patients with mild cognitive impairment (Nikolova et al, 2017) and Alzheimer's disease (Walecki et al, 2011). Then, an increased cortical MD, which has been observed in aging and the above-mentioned diseases (Lin et al, 2016;Ni et al, 2010;Ray et al, 2006;Weston et al, 2015), may reflect the decline in the magnitude of microstructural organization in the GM associated with aging and age-related diseases, i.e.…”