phosphocreatine and Cognition-Disorders

The objective of the investigation was to compare possibilities how to influence the general neuropsychic symptomatology described as cardiocerebral syndrome during the first three days of an acute myocardial infarction (AIM) in old age by means of creatine phosphate (CP).. The investigation which extended over 8 months comprised 50 subjects admitted to the coronary unit (CU) because of AIM symptomatology, age 65-93 years (75.1 +/- 5.6 years). Twenty-five subjects were given, using a uniform protocol, during the first three days at the CU, 18 g CP (Neoton, Schiapparelli) by the i.v. rut. The control group of 25 subjects (randomized) with AIM of comparable parameters (age, sex, location and course of IM) were not given CP. Evaluation of the dynamics of mental deterioration by means of a test of cognitive functions (MMS) during the first three days after IM by means of simple regression analysis, comparing the two groups, revealed a favourable effect of CP on mental functions as compared with the control group (p = 0.05). In the CP treated group there was, as compared with the control group, on the 1st and 2nd day a lower incidence of stenocardias (statistically not significant; p = NS), ventricular dysrhythmias (p = NS) and cardiac failure (p = NS).. Administration of creatine phosphate did not produce any undesirable side effects. Objective evidence was provided of the favourable effect of CP on mental deterioration in cardiocerebral syndrome in AIM in old age.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Female; Humans; Male; Myocardial Infarction; Phosphocreatine

The second-largest cause of X-linked mental retardation is a deficiency in creatine transporter (CRT; encoded by SLC6A8), which leads to speech and language disorders with severe cognitive impairment. This syndrome, caused by the absence of creatine in the brain, is currently untreatable because CRT is required for creatine entry into brain cells. Here, we developed a brain-specific Slc6a8 knockout mouse (Slc6a8-/y) as an animal model of human CRT deficiency in order to explore potential therapies for this syndrome. The phenotype of the Slc6a8-/y mouse was comparable to that of human patients. We successfully treated the Slc6a8-/y mice with the creatine analog cyclocreatine. Brain cyclocreatine and cyclocreatine phosphate were detected after 9 weeks of cyclocreatine treatment in Slc6a8-/y mice, in contrast to the same mice treated with creatine or placebo. Cyclocreatine-treated Slc6a8-/y mice also exhibited a profound improvement in cognitive abilities, as seen with novel object recognition as well as spatial learning and memory tests. Thus, cyclocreatine appears promising as a potential therapy for CRT deficiency.

Topics: Animals; Base Sequence; Brain; Cognition; Cognition Disorders; Creatinine; Disease Models, Animal; DNA Primers; Female; Humans; Imidazolidines; Learning; Male; Membrane Transport Proteins; Memory; Mental Retardation, X-Linked; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Neurological; Phosphocreatine

Although magnetic resonance spectroscopy has identified metabolic abnormalities in adult and childhood schizophrenia, no prior studies have investigated the relationship between neurometabolites and thought disorder. This study examined this association in language-related brain regions using proton magnetic resonance spectroscopic imaging ((1)H MRSI).. MRSI was acquired bilaterally from 28 youth with childhood-onset schizophrenia and 34 healthy control subjects in inferior frontal, middle frontal, and superior temporal gyri at 1.5T and short echo time (TR/TE = 1500/30 ms). CSF-corrected "total NAA" (tNAA; N-acetyl-aspartate + N-acetyl-aspartyl-glutamate), glutamate + glutamine (Glx), creatine + phosphocreatine (Cr + PCr), choline compounds (Cho), and myo-inositol (mI) were assayed in manually drawn regions-of-interest partitioned into gray matter, white matter, and CSF and then coregistered with MRSI. Speech samples of all subjects were coded for thought disorder.. In the schizophrenia group, the severity of formal thought disorder correlated significantly with tNAA in the left inferior frontal and superior temporal gyri and with Cr + PCr in left superior temporal gyrus.. Neurometabolite concentrations in language-related brain regions are associated with thought disorder in childhood-onset schizophrenia.

Topics: Adolescent; Analysis of Variance; Aspartic Acid; Brain; Child; Choline; Cognition Disorders; Creatine; Dipeptides; Female; Humans; Magnetic Resonance Spectroscopy; Male; Neuropsychological Tests; Phosphocreatine; Protons; Psychiatric Status Rating Scales; Schizophrenia, Childhood; Statistics, Nonparametric

Single-voxel proton magnetic resonance imaging ((1)H-MRS) and proton MR spectroscopic imaging ((1)H-MRSI) were used to compare brain metabolite levels in semi-acute mild traumatic brain injury (mTBI) patients (n = 10) and matched healthy controls (n = 9). The (1)H-MRS voxel was positioned in the splenium, a region known to be susceptible to axonal injury in TBI, and a single (1)H-MRSI slice was positioned above the lateral ventricles. To increase sensitivity to the glutamate (Glu) and the combined glutamate-glutamine (Glx) signal, an inter-pulse echo time shown to emphasize the major Glu signals was used along with an analysis method that reduces partial volume errors by using water as a concentration standard. Our preliminary findings indicate significantly lower levels of gray matter Glx and higher levels of white matter creatine-phosphocreatine (Cr) in mTBI subjects relative to healthy controls. Furthermore, Cr levels were predictive of executive function and emotional distress in the combined groups. These results suggest that perturbations in Cr, a critical component of the brain's energy metabolism, and Glu, the brain's major neurotransmitter, may occur following mTBI. Moreover, the different pattern of results for gray and white matter suggests tissue-specific metabolic responses to mTBI.

Topics: Adult; Affective Symptoms; Axons; Biomarkers; Body Water; Brain; Brain Injuries; Cognition Disorders; Corpus Callosum; Creatine; Diffuse Axonal Injury; Energy Metabolism; Female; Glutamic Acid; Glutamine; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Middle Aged; Nerve Fibers, Myelinated; Phosphocreatine; Young Adult

Involvement of the prefrontal cortex in schizophrenia has been implicated by neuropsychological, as well as neuropathological and imaging studies. Reductions of N-acetylaspartate (NAA), an in vivo marker of neuronal integrity, have repeatedly been detected in the frontal lobes of patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). In chronic medicated patients, a positive correlation between NAA levels of the prefrontal cortex and cognitive functioning has been observed, but to date, there have been no studies in first-episode neuroleptic-naive patients. In this study, single-voxel 1H-MRS was used to investigate neuronal function of the dorsolateral prefrontal cortex in 15 first-episode and 20 chronic schizophrenic patients. Outcomes were compared to 20 age-matched healthy controls to assess the relationship between prefrontal metabolism and neuropsychological performance. Patients with chronic schizophrenia had significant reductions of NAA, glutamate/glutamine, and choline levels compared to first-episode patients and healthy controls. Furthermore, creatine and phosphocreatine were significantly reduced in both patient groups compared to healthy controls. In the neuropsychological tests, chronic schizophrenic patients performed significantly poorer in the Auditory Verbal Learning Task (AVLT) compared to first-episode patients. In both patient groups, NAA levels of the left frontal lobe significantly correlated with performances in verbal learning and memory. These results corroborate data from recent structural and spectroscopic imaging studies of the frontal lobes in schizophrenia, in which cortical gray matter reductions after onset of symptoms as well as reduced levels of NAA in chronic, but not in first-episode schizophrenic patients have been reported.

Topics: Adult; Aged; Antipsychotic Agents; Aspartic Acid; Choline; Chronic Disease; Cognition Disorders; Creatine; Dominance, Cerebral; Energy Metabolism; Female; Frontal Lobe; Glutamic Acid; Glutamine; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mental Recall; Middle Aged; Neurons; Phosphocreatine; Prefrontal Cortex; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Verbal Learning

We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry. In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores. The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence. These conclusions are deemed preliminary due t

Topics: Adult; Anxiety Disorders; Body Mass Index; Choline; Cognition Disorders; Creatine; Frontal Lobe; Functional Laterality; Humans; Magnetic Resonance Spectroscopy; Phosphocreatine; Prosencephalon; Protons; Regression Analysis; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Time Factors; Wechsler Scales

Obstructive sleep apnea (OSA) is associated with intermittent hypoxia and cognitive decrements. As the hippocampus is particularly susceptible to hypoxia, we hypothesized that it may show biochemical abnormalities, and they may relate to apnea severity.. Eight males with OSA and five age-matched controls underwent neurocognitive testing before and after polysomnography and proton magnetic resonance spectra were obtained from the left hippocampal area of all subjects.. In the left hippocampal area, N-acetyl-containing/creatine-containing compounds was significantly increased in OSA (P=0.04). Inspection of these compounds with respect to the water resonance indicated that this was most likely due to a decrease in creatine-containing compounds rather than any change in N-acetyl-containing compounds. Lower levels of hippocampal creatine-containing compounds were correlated with worse OSA severity and neurocognitive performance.. We suggest the changes in creatine levels in the hippocampal area represent adjustments to brain bioenergetics, similar to those seen in ischemic preconditioning, and may reflect the different susceptibility of these tissues to hypoxic damage in OSA.

Topics: Adult; Arousal; Aspartic Acid; Cognition Disorders; Electroencephalography; Female; Hippocampus; Humans; Hypoxia, Brain; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neuropsychological Tests; Phosphocreatine; Polysomnography; Psychomotor Performance; Severity of Illness Index; Sleep Apnea, Obstructive; Sleep Stages

In a previous proton magnetic resonance spectroscopic imaging ((1)H MRSI) study of the hippocampus in patients receiving electroconvulsive therapy (ECT), the metabolite signals for N-acetylaspartate (NAA), creatine and phosphocreatine, and choline-containing compounds (Ch) were evaluated before and directly after a course of ECT. Stable metabolite signals for NAA and creatine and phosphocreatine but increasing signals from choline-containing compounds post-ECT compared with pre-ECT were found. The purpose of this investigation was to monitor the long-term course of the hippocampal metabolite signals post-ECT treatment.. Twelve of 17 depressed patients (DSM-IV and ICD-10 criteria), examined while receiving ECT, were reevaluated after a minimum interval of 12 months. Data were gathered between 1997 and 2000. In all patients, (1)H MRSI studies of the hippocampus were performed and relative contributions of cerebrospinal fluid, gray matter, and white matter to each MRSI voxel were determined. Patients' cognitive as well as psychopathologic status was obtained.. Two of the examined patients suffered a relapse. All other patients were in stable remission. No changes in hippocampal NAA signals were detected after a mean interval of 20 months (SD = 8.6) after the last ECT. The initially significant increase in the Ch signal was found to be reversed to nearly pre-ECT values.. The results of our long-term follow-up corroborate our original finding that ECT has no influence on NAA signals. The observed reversal of the Ch signal might reflect alterations in membrane turnover. Increased Ch signals are thought to reflect an increased membrane turnover and should reverse accordingly. This increase in membrane turnover could potentially play a role in the therapeutic effect of ECT.

Topics: Aspartic Acid; Choline; Cognition Disorders; Creatine; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Follow-Up Studies; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neuropsychological Tests; Phosphocreatine; Recurrence; Severity of Illness Index; Signal Transduction; Time Factors

Parkinsonism is a common neurological sequela of carbon monoxide (CO) poisoning, but its pathophysiological mechanism has yet to be clarified.. To describe a married couple who were both affected by CO poisoning, but only 1 of whom developed CO-induced parkinsonism, and to discuss the possible underlying pathophysiological mechanism of CO-induced parkinsonism by comparing the neuroimaging findings of these patients.. Case report from a clinical neurology department.. A married couple experienced CO poisoning simultaneously. One month later, only the husband gradually developed delayed sequelae, including parkinsonism and intellectual impairment. On detailed neurological examination, the husband showed mild but definite rigidity and bradykinesia, while no parkinsonian signs were observed in the wife. Neuropsychological examination revealed impaired memory and attention in both patients, but they were more severe in the husband than in the wife. Magnetic resonance imaging scans of the patients' brains disclosed diffuse high-intensity white matter signals in both patients and bilateral pallidal necrosis in the wife. Dopamine transporter imaging showed that the degree of dopamine neuronal loss was comparable between these patients. Magnetic resonance spectroscopy revealed more severe white matter damage in the husband than in the wife. Thirteen months later, neurological and neuropsychological examinations showed complete recovery from parkinsonism as well as intellectual impairment. Follow-up magnetic resonance spectroscopy also suggested remarkable improvements in white matter damage.. These results support the role of white matter damage in producing parkinsonism after CO poisoning and highlight the possible usefulness of magnetic resonance spectroscopy in predicting delayed sequelae in patients after CO poisoning. Arch Neurol. 2000;57:1214-1218

Topics: Aspartic Acid; Brain Chemistry; Carbon Monoxide Poisoning; Carrier Proteins; Choline; Cognition Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Phosphocreatine; Tomography, Emission-Computed, Single-Photon

To study how neuronal cells are affected by development of chronic cerebral vasospasm after subarachnoid hemorrhage (SAH), the changes in neuronal metabolites during development of vasospasm were evaluated by in vivo localized proton magnetic resonance spectroscopy (MRS) in primates.. SAH was produced by introduction of a blood clot around the right middle cerebral artery and the right side of the circle of Willis. MRS experiments were performed before SAH and on Days 7 and 14 after SAH. Multislice magnetic resonance images were obtained to locate the volume of interest (1.0 cm3) in the bilateral parietal regions. The peak areas for choline compounds, the sum of creatine and phosphocreatine, and N-acetyl-aspartate were calculated.. Angiograms revealed approximately 50% reduction of vessel caliber for the right main cerebral arteries on Day 7. Magnetic resonance imaging revealed no apparent cerebral infarction, even in the spasm-side hemisphere. MRS revealed a significant (P < 0.05) reduction of the N-acetyl-aspartate/creatine and phosphocreatine ratio on Days 7 and 14 and a significant increase in the choline/creatine and phosphocreatine ratio on Day 7, in the spasm-side parietal region. In the sham-operated animals, there were no significant changes in these ratios in the bilateral parietal region on Days 7 and 14 after the operation.. The results suggested that the development of cerebral vasospasm after SAH caused ischemic injury in a subpopulation of neuronal cells, even when no apparent cerebral infarction was shown. Proton MRS may be useful to evaluate how neuronal cells are affected by the ischemic insult during development of vasospasm in clinical situations.

Topics: Animals; Aspartic Acid; Brain; Brain Ischemia; Cerebral Angiography; Cerebrovascular Circulation; Choline; Chronic Disease; Cognition Disorders; Creatinine; Energy Metabolism; Female; Ischemic Attack, Transient; Macaca fascicularis; Magnetic Resonance Imaging; Neurons; Phosphocreatine; Subarachnoid Hemorrhage