Meta-Analysis of Neurochemical Changes Estimated via Magnetic Resonance Spectroscopy in Mild Cognitive Impairment and Alzheimer's Disease

Abstract

The changes of neurochemicals in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients has been observed via magnetic resonance spectroscopy in several studies. However, whether it exists the consistent pattern of changes of neurochemicals in the encephalic region during the progression of MCI to AD were still not clear. The study performed meta-analysis to investigate the patterns of neurochemical changes in the encephalic region in the progress of AD. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases, and finally included 63 studies comprising 1,086 MCI patients, 1,256 AD patients, and 1,907 healthy controls. It showed that during the progression from MCI to AD, N-acetyl aspartate (NAA) decreased continuously in the posterior cingulate (PC) (SMD: −0.42 [95% CI: −0.62 to −0.21], z = −3.89, P < 0.05), NAA/Cr (creatine) was consistently reduced in PC (SMD: −0.58 [95% CI: −0.86 to −0.30], z = −4.06, P < 0.05) and hippocampus (SMD: −0.65 [95% CI: −1.11 to −0.12], z = −2.44, P < 0.05), while myo-inositol (mI) (SMD: 0.44 [95% CI: 0.26–0.61], z = 4.97, P < 0.05) and mI/Cr (SMD: 0.43 [95% CI: 0.17–0.68], z = 3.30, P < 0.05) were raised in PC. Furthermore, these results were further verified by a sustained decrease in the NAA/mI of PC (SMD: −0.94 [95% CI: −1.24 to −0.65], z = −6.26, P < 0.05). Therefore, the levels of NAA and mI were associated with the cognitive decline and might be used as potentially biomarkers to predict the possible progression from MCI to AD.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020200308.

A Comparative study of Posterior cingulate metabolism in Patients with Mild Cognitive Impairment due to Parkinson’s Disease or to Alzheimer’s Disease

“…In ADMCI, the PCC metabolic pattern is one that is well documented in the literature (Liu et al, 2021), consisting of elevated Ins concentration or Ins/Cr ratio (Mitolo et al, 2019;Waragai et al, 2017). It has been suggested that increased Ins/Cr in ADMCI possibly represents gliosis or is a marker of in ammation (Kantarci et al, 2007;Kantarci et al, 2009).…”

“…Proton Magnetic resonance spectroscopy ( 1 H-MRS)(Ciurleo, Di Lorenzo, Bramanti, & Marino, 2014; Gujar, Maheshwari, Bjorkman-Burtscher, & Sundgren, 2005) is a potential option for identifying neurobiomarkers of cognitive status, which can be used to investigate brain metabolites like N-acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (Ins), glutamine (Gln), and glutamate (Glu), and also provide information about neuronal integrity (NAA), membrane turnover (Cho), glial metabolism (mIns), energy metabolism (Cr), and glutamatergic neuronal activity (Glu, Gln) in patients. Abnormal metabolic ratios (NAA/Cr, Cho/Cr and mI/Cr) or metabolic absolute concentration in the posterior cingulate cortex (PCC) have been identi ed in AD, as well as mild cognitive impairment (Liu et al, 2021;Mitolo et al, 2019). A recent 7-year follow-up study suggest that cognitively normal elderly subjects with low NAA/MI ratios in the PCC might be at risk of preclinical AD (Waragai, Moriya, & Nojo, 2017).…”

Taurine Supplementation as a Neuroprotective Strategy upon Brain Dysfunction in Metabolic Syndrome and Diabetes

“…Little attention has been given to taurine concentrations measured by MRS in the brain of AD patients relative to those in healthy individuals ([ 164 , 165 ] and references therein). That is because most MRS studies were conducted at low magnetic fields.…”

Neurometabolic correlates of posturography in normal aging and older adults with mild cognitive impairment: Evidence from a 1H-MRS study

“…Alterations in neurometabolite concentrations or neurometabolite ratios have also been shown to play a pivotal role as mediators of progressive performance declines observed in older adults with MCI or patients with dementia-related disorders (e.g., Kantarci et al, 2002 , Lyros et al, 2020 , Mitolo et al, 2019 , Oeltzschner et al, 2019 ). Specifically, low tNAA/tCr and elevated mIns/tCr and tCho/tCr in posterior cingulate cortex and/or hippocampus were reported as early predictors of transition from MCI to Alzheimer’s disease ( Liu et al, 2021 , Zhao et al, 2021 ). Finally, elevated levels of mIns in hippocampus and high levels of tCho and glutamate in the anterior cingulate cortex were found to be associated with worse performance on a working memory task as well as elevated low-grade systemic inflammation ( Lind et al, 2021 , Vints et al, 2022 ).…”

“…We focused specifically on possible associations between balance performance and expressions of tNAA/tCr tCho/tCr and mIns/tCr in hippocampus, hippocampal gyrus, posterior cingulate cortex, sensorimotor cortex, and prefrontal cortex. We hypothesized that (1) lower tNAA/tCr and elevated tCho/tCr and mIns/tCr, which are considered as biomarkers of neurodegeneration and neuroinflammation, respectively (e.g., Lind et al, 2020 , Liu et al, 2021 , Vints et al, 2022 , Zhao et al, 2021 ), would be related to reduced balance performance in general. Moreover, we hypothesized that (2) specific neurometabolic markers of neurodegeneration (tNAA/tCr) and neuroinflammation (mIns/tCr and tCho/tCr) in the hippocampus would predict worse balance performance of older individuals with MCI more than normative older adults.…”