Clinical Studies | Memory Disorders


CLINICAL STUDY 1 — Tyrosine Improves Working Memory in a Multitasking Environment

—Thomas JR, Lockwood PA, Singh A, Deuster PA. – Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences

Previous studies indicate that tyrosine may prove useful in promoting improved performance in situations in which performance is compromised by stress. To extend the generality of previous tyrosine findings, the present study examined the effects of tyrosine ingestion on performance during both a Multiple Task and a Simple Task battery. The multiple task battery was designed to measure working memory, arithmetic skills, and visual and auditory monitoring simultaneously, whereas the simple task battery measured only working memory and visual monitoring. Ten men and 10 women subjects underwent these batteries 1 h after ingesting 150 mg/kg of l-tyrosine or placebo. Administration of tyrosine significantly enhanced accuracy and decreased frequency of list retrieval on the working memory task during the multiple task battery compared with placebo. However, tyrosine induced no significant changes in performance on the arithmetic, visual, or auditory tasks during the Multiple Task, or modified any performance measures during the Simple Task battery. Blood levels of ACTH and cortisol were not, but heart rate and blood pressure were significantly increased during the performance tasks. The present results indicate that tyrosine may sustain working memory when competing requirements to perform other tasks simultaneously degrade performance, and that supplemental tyrosine may be appropriate for maintaining performance when mild to severe decrements are anticipated. PMID: 10548261

(phenylalanine is the precursor to tyrosine)

CLINICAL STUDY 2 — Tyrosine Supplementation Mitigates Working Memory Decrements During Cold Exposure

—Mahoney CR, Castellani J, Kramer FM, Young A, Lieberman HR. – US Army Soldier Research, Development and Engineering Center, Kansas Street, Natick, MA

In rats, dietary supplementation with the amino acid tyrosine (TYR) prevents depletion of central catecholamines observed during acute environmental stress. Concomitant changes in the animals’ behavioral responses to stress suggest that TYR might have similar effects on central catecholamines and cognition in humans exposed to environmental stress. This study aimed to determine if severe cold exposure impairs human cognition and if dietary supplementation with TYR would ameliorate such deficits. Volunteers (N=19) completed three test sessions on different days (35 degrees C control/placebo, approximately 10 degrees C/placebo, approximately 10 degrees C/TYR) using a double-blind, within subjects design. During each session, volunteers completed two 90-minute water immersions and consumed a food bar (150 mg/kg TYR or placebo) before each immersion (total TYR 300 mg/kg). Cognitive performance, mood, and salivary cortisol were assessed. Cortisol was elevated in the cold (p<.01). Volunteers made fewer correct responses on a Match-to-Sample memory measure (p<.05) and reaction time (RT) and errors increased on a choice RT test (p<.01) in the cold. Self-reported tension (p<.01), depression (p<.05) and confusion (p<.01) also increased in the cold. When volunteers consumed TYR, correct responses increased on a Match-to-Sample memory measure (p<.05) and study time for the sample was shorter (p<.05), indicative of more rapid and accurate information processing. Finally, RT on the memory measure revealed a similar pattern across immersions for TYR and thermoneutral conditions, but not cold/placebo (p<.05). This study demonstrates cold exposure degrades cognitive performance and supplementation with TYR alleviates working memory decrements. PMID: 17585971

(phenylalanine is the precursor to tyrosine)

CLINICAL STUDY 3 — Effect of Tyrosine on Cognitive Function and Blood Pressure under Stress

—Deijen JB, Orlebeke JF. – Department of Psychophysiology, Vrije Universiteit, Amsterdam, The Netherlands

The effects of tyrosine on mood, performance, heart rate and blood pressure of 16 healthy young subjects were assessed. Subjects were tested on two separate days, one test session after ingestion of 100 mg/kg tyrosine and the other test session after placebo, in random order. While performing a number of stress sensitive tasks, subjects were exposed to a stressor consisting of 90 dB noise. tyrosine was found to improve the performance on two cognitive tasks, which were performed 1 h after administration of the medication and which could be characterized as highly sensitive to stress. In addition, tyrosine decreased diastolic blood pressure 15 min after ingestion, while 1 h after ingestion diastolic blood pressure was the same with tyrosine and placebo. No effects on mood, systolic blood pressure and heart rate were found. PMID: 8293316

(phenylalanine is the precursor to tyrosine)

CLINICAL STUDY 4 — L-Dopa Modulates Motor Cortex Excitability in Alzheimer’s Disease Patients

—Martorana A, Stefani A, Palmieri MG, Esposito Z, Bernardi G, Sancesario G, Pierantozzi M. – Dipartimento di Neuroscienze, Clinica Neurologica, Università di Roma, “Tor Vergata”, via Montpellier, 1, 00133 Rome, Italy

In Alzheimer’s disease (AD), transcranial magnetic stimulation (TMS) studies have shown abnormalities of motor cortical excitability, such as a decreased intra-cortical inhibition (ICI) and changes in resting motor threshold (rMT). We studied the effects of l-dopa on rMT and ICI in a cohort of moderate AD patients after paired-pulse TMS. Results were compared with a control group of healthy subjects. As expected, AD patients showed a significant reduction in ICI and a lower rMT. L-dopa administration (soluble form, melevodopa 200 mg) promptly reversed the ICI impairment up to normalization. This effect was specific, since it was not mimicked in control subjects. These results indicate a possible role of dopamine in modulating AD cortical excitability, thus suggesting an interaction between dopaminergic ascending pathways and endogenous intracortical transmitters. In addition, considering that l-dopa showed a pharmacological profile similar to the one of cholinomimetics, l-dopa might represent a reliable tool to study new therapeutic perspective and strategies for AD. PMID: 18594753

(phenylalanine is the precursor to tyrosine, which in turn is the precursor to l-dopa)

CLINICAL STUDY 5 — Glutamate-Glutamine Cycling in Alzheimer’s Disease

—Walton HS, Dodd PR. – School of Molecular and Microbial Science, University of Queensland, Australia

In addition to its definitive pathological characteristics, neuritic plaques and neurofibrillary tangles, Alzheimer’s disease (AD) brain exhibits regionally variable neuronal loss and synaptic dysfunction that are likely to underlie the sympatic memory loss and language abnormalities. A number of mechanisms that could give rise to this localized damage have been proposed, amongst which excitotoxicity figures prominently. This is the process, well attested in experimental systems, whereby brain cells are excited to death by the pathophysiological action of the brain’s most-abundant excitatory transmitter, glutamate. Glutamate transmission is mediated by a range of ionotropic and metabotropic receptors which, when activated, can lead to depolarization and increased intracellular Ca2+ ion concentration in the cells on which they are located. The action of glutamate is terminated by its removal from these receptor sites by transport into nearby cells, most commonly perisynaptic astrocytes. There it is converted to physiologically inert glutamine and shuttled back to excitatory nerve terminals. Malfunctions in components of the glutamate-glutamine cycle could result in a self-perpetuating neuronal death cascade mediated by glutamate. The approval by the FDA of an ionotropic glutamate receptor antagonist to treat late-stage AD has led to renewed interest in the contribution of altered glutamatergic neurotransmission to disease pathogenesis. This review encompasses those aspects of glutamate-glutamine cycling that are altered in AD. PMID: 17141374

CLINICAL STUDY 6 — GABAA Receptors: Properties and Trafficking

—Michels G, Moss SJ. – Department of Neuroscience, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA

Fast synaptic inhibition in the brain and spinal cord is mediated largely by ionotropic gamma-aminobutyric acid (GABA) receptors. GABAA receptors play a key role in controlling neuronal activity; thus modulating their function will have important consequences for neuronal excitation. GABAA receptors are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are involved in a number of CNS diseases, including sleep disturbances, anxiety, premenstrual syndrome, alcoholism, muscle spasms, Alzheimer’s disease, chronic pain, schizophrenia, bipolar affective disorders, and epilepsy. This review focuses on the functional and pharmacological properties of GABAA receptors and trafficking as an essential mechanism underlying the dynamic regulation of synaptic strength. PMID: 17364682

(l-glutamine is the precursor to gamma-aminobutyric acid GABA)

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