Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype

Abstract

The biomarker potential of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer’s disease has not yet been explored. We measured GABA, glutamate + glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound B-positive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid β deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer’s disease.

Neurochemical Modulation in Posteromedial Default-mode Network Cortex Induced by Transcranial Magnetic Stimulation

“…Importantly, GABA responsiveness assessed with MRS has already been linked to plasticity responses such as learning mechanisms in the human motor cortex [37,38]. On the other side, basal posteriomedial GABA concentrations seems to be decreased in aging [18] and in amnestic mild cognitive impairment [17] as well as it proved sensitive enough to detect pharmacological interventions in the latter condition [63].…”

“…Intrinsic functional connectivity of the DMN is also mediated by GABA and glutamate [16]. Complementarily, MRS neurotransmitter measures in the DMN are sensitive to healthy and pathological aging [17,18].…”

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

“…For inclusion, subjects had to be aged between 55 and 80 years. Cognitive health was ascertained by a Mini-Mental State Examination (MMSE) score of !27 and clinical examination that included clinical workup and neuropsychological testing (see also Riese et al, 2015;Steininger et al, 2014). Exclusion criteria were as follows: significant medication or drug abuse that may affect cognition, magnetic resonance imaging (MRI) exclusion criteria, contraindications against venipuncture, clinically relevant changes in red blood cell count, allergy to PiB or any of its constituents, history of severe allergic reactions to drugs or allergens, critical or medically unstable illness, pregnancy or lactation, and significant exposure to radiation.…”

“…PET acquisition has been published before (Riese et al, 2015;Steininger et al, 2014). An antecubital venous line was positioned for the application of approximately 350 MBq of PiB.…”

Large-scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses

“…There is strong evidence that glutamatergic excitation, GABAergic inhibition and balanced E/I are altered in older adults and psychiatric patients relative to younger adults and healthy controls (HCs), respectively, and that unbalanced E/I contributes to impaired cognitive functioning (Brady et al, 2013; Caspary et al, 2008; Edden et al, 2012; El Idrissi et al, 2013; Ende et al, 2016; Gonzalez-Burgos et al, 2015; Legon et al, 2015; Luscher and Fuchs, 2015; Murray et al, 2014; Nelson and Valakh, 2015; Pehrson and Sanchez, 2015; Purkayastha et al, 2015; Riese et al, 2015; Robertson et al, 2016; Roux and Buzsaki, 2015; Schmidt and Mirnics, 2015; Stebbings et al, 2016; Tse et al, 2015). This pathophysiological mechanism may contribute importantly to inconsistent GLM findings because they may lead to BOLD signal decrease, increase, or no change in different brain regions in older adults and patients, depending on the relative extent of changes in excitation and inhibition in each region.…”