Is there a relationship between low-grade systemic inflammation and cognition in healthy people aged 60-75 years?

Although inflammation has been associated with cognitive impairment in dementia, less is known about its role in the cognition of middle to older aged healthy people. This study utilised baseline data from the Australian Research Council Longevity Intervention (ARCLI) trial to investigate the relationship between markers of systemic inflammation (TNF-α, IL-6, IL-1ß, INF-γ, IL-2, IL-4, IL-10 and hsCRP) and cognitive function in 286 healthy volunteers aged 60-75 years. We assessed cognitive functioning across domains including attention, speed of memory, working memory and episodic memory using the Cognitive Drug Research test battery. Only IFN-γ was related to cognitive function, being associated with greater odds of having low continuity of attention (log2 IFN-γ OR, 1.46; 95 % CI, 1.18-1.85). The relationship between episodic memory, speed of memory and inflammation varied with BMI. In high BMI participants, increased inflammation was associated with worse cognitive function, while this association was reversed in those with low BMI. Outside of the influence of IFN-γ on attention, low-grade systemic inflammation was not robustly associated with cognitive function in this sample of middle to older aged healthy people. Further research is required to understand the role of BMI in the intersection of inflammation and cognitive function.

Driving impairment due to propofol at effect-site concentrations relevant after short propofol-only sedation.

Australian guidelines state "Following brief surgery or procedures with short acting anaesthetic drugs, the patient may be fit to drive after a normal night's sleep. After long surgery or procedures requiring longer lasting anaesthesia, it may not be safe to drive for 24 hours or more". The increasing use of the short-acting anaesthetic drug propofol as a solitary sedative medication for simple endoscopy procedures suggests a need to review this blanket policy. Thirty patients presenting for elective day surgery were recruited as volunteers for a pre-procedure driving simulation study and randomised to propofol or placebo arms. Driving ability was assessed at baseline and then, in the propofol group, at three effect-site concentrations. Driving impairment at these concentrations of propofol was compared to that of a third group of volunteers with a blood alcohol concentration of 0.05% (g/100 ml). Driving impairment at 0.2 µg/ml propofol effect-site concentration was not statistically different to placebo. Impairment increased with propofol effect-site concentration (P=0.002) and at 0.4 µg/ml it was similar to that found with a blood alcohol concentration of 50 mg/100 ml (0.05%). Plasma propofol concentrations of 0.2 µg/ml, as might be found approximately an hour after short (<1 hour duration) propofol-only sedation for endoscopy, were not associated with driving impairment in our young cohort of volunteers.

The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment.

Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects.

The neurocognitive effects of Hypericum perforatum Special Extract (Ze 117) during smoking cessation.

The efficacy and tolerability of current treatments for smoking cessation are relatively poor. More research is required to address the biological mechanisms underpinning nicotine withdrawal and drug treatments for smoking cessation. We assessed the neurocognitive effects of Remotiv® (Hypericum perforatum Special Extract - Ze 117), Nicabate CQ Nicotine Replacement therapy (NRT) and combined NRT/HP during conditions of smoking abstinence in 20 regular smokers aged between 18 and 60 years over a period of 10 weeks during smoking cessation. A Spatial Working Memory (SWM) task was completed at baseline, 4 weeks prior to quitting, as well as at the completion of the study, following the 10 weeks of treatment. Brain activity was recorded during the completion of the SWM task using Steady-State Probe Topography. Reaction time and accuracy on the SWM task were not found to be significantly different between treatment groups at retest. Differences in SSVEP treatment profiles at retest are discussed, including stronger SSVEP Amplitude increase in posterior-parietal regions for the HP and NRT groups and greater fronto-central SSVEP Phase Advance in the HP group.

Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.

Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.

Does a medicinal dose of kava impair driving? A randomized, placebo-controlled, double-blind study.

OVERVIEW: Increasing concerns over the potentially impairing effects of prescriptive sedative drugs such as benzodiazepines on driving have been raised. However, other alternatives such as natural medicines may also carry similar risks with respect to driving safety. Kava (Piper methysticum) is a psychotropic plant commonly used both recreationally and medicinally in the United States, Australia, and the South Pacific to elicit a physically tranquilizing effect. To date no controlled study has tested a medicinal dose of kava versus placebo and a standard sedative drug on driving ability and driving safety. OBJECTIVE: Due to the need to establish the safety of kava in operating a motor vehicle, we compared the acute effects of the plant extract versus the benzodiazepine oxazepam and placebo using a driving simulator. METHODS: A driving simulator (AusEd) was used by 22 adults aged between 18 and 65 years after being randomly administered an acute medicinal dose of kava (180 mg of kavalactones), oxazepam (30 mg), or placebo one week apart in a crossover design trial. RESULTS: No impairing effects on driving outcomes were found after kava administration compared to placebo. Results on specific driving outcome domains revealed that the oxazepam condition had significantly slower braking reaction time compared to the placebo condition (p =.002) and the kava condition (p =.003). The kava condition had significantly fewer lapses of concentration compared to the oxazepam condition (p =.033). No significant differences were found between conditions for steering deviation, speed deviation, and number of crashes. Results were not modified by driving experience. On the Bond-Lader visual analogue sub-scale of alertness, a significant Treatment × Time interaction (p =.032) was found, with a significant reduction over time for oxazepam decreasing alertness (p <.001), whereas no significant reduction was found in the kava or placebo conditions. CONCLUSION: The results indicate that a medicinal dose of kava containing 180 mg of kavalactones does not impair driving ability, whereas 30 mg of oxazepam shows some impairment. Research assessing larger recreational doses of kava on driving ability should now be conducted.

The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study.

RATIONALE: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines. METHODS: Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial. RESULTS: After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial ŋ² = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava. CONCLUSION: Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition.

The acute effects of d-amphetamine and d-methamphetamine on ERP components in humans.

While a number of behavioural studies have been conducted to investigate the acute effects of amphetamines on tasks of attention and information processing, there is currently a scarcity of research concerning their electrophysiological effects in healthy adults. It is also unclear as to whether amphetamines exert effects on stimulus evaluation or response selection. In two studies, independent groups of twenty healthy illicit stimulant users aged between 21 and 32 years were administered 0.42 mg/kg d-amphetamine versus placebo, and 0.42 mg/kg d-methamphetamine versus placebo respectively, and completed an auditory oddball task on two separate testing days. A 62-channel EEG was recorded during the completion of the task, and the effects of amphetamines on N200 and P300 ERP components were analysed. d-amphetamine significantly decreased reaction time, improved accuracy, and reduced the latency of the P300 component relative to placebo, while having no effect on the N200 component. d-methamphetamine had no effect on reaction time, accuracy or the P300 component, but reduced the amplitude of the N200 component, relative to placebo. It was concluded that there is tentative support to suggest that d-amphetamine at a dose of 0.42 mg/kg may enhance speed of information processing while d-methamphetamine at a dose of 0.42 mg/kg may reflect changes to stimulus evaluation.

Steady state visually evoked potential (SSVEP) topography changes associated with cocoa flavanol consumption.

In a randomized, double-blind placebo controlled trial, 63 middle-aged volunteers aged between 40 and 65 years were administered a daily chocolate drink containing 250 mg or 500 mg cocoa flavanols versus a low cocoa flavanol (placebo) drink over a 30-day period. Participants were tested at baseline as well as at the end of the treatment period on a test of Spatial Working Memory. Steady State Probe Topography (SST) was used to assess neurocognitive changes associated with cocoa flavanol supplementation during the completion of the Spatial Working Memory task. SST is an electrophysiological technique which utilizes a 13 Hz diffuse visual flicker in order to generate a steady state visually evoked potential (SSVEP). Changes in the amplitude and phase of the SSVEP response after 30 days were compared between treatment groups. Behavioral measures of accuracy and reaction time were not found to be significantly different between treatment groups, while average SSVEP amplitude and phase differences at a number of posterior parietal and centro-frontal sites were found to be significantly different between groups during memory encoding, the working memory hold period and retrieval. In the absence of significant behavioral effects, these differences in brain activation can be interpreted as evidence of increased neural efficiency in spatial working memory function associated with chronic cocoa flavanol consumption.

Examining brain-cognition effects of ginkgo biloba extract: brain activation in the left temporal and left prefrontal cortex in an object working memory task.

Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM) associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50-61 year old) male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order. For both groups, SSVEP was recorded from 64 scalp electrode sites during the completion of an object WM task both pre- and 14 days post-treatment. GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion.

A randomized, controlled trial of meditation for work stress, anxiety and depressed mood in full-time workers.

Objective. To assess the effect of meditation on work stress, anxiety and mood in full-time workers. Methods. 178 adult workers participated in an 8-week, 3-arm randomized controlled trial comparing a "mental silence" approach to meditation (n = 59) to a "relaxation" active control (n = 56) and a wait-list control (n = 63). Participants were assessed before and after using Psychological Strain Questionnaire (PSQ), a subscale of the larger Occupational Stress Inventory (OSI), the State component of the State/Trait Anxiety Inventory for Adults (STAI), and the depression-dejection (DD) subscale of the Profile of Mood States (POMS). Results. There was a significant improvement for the meditation group compared to both the relaxation control and the wait-list groups the PSQ (P = .026), and DD (P = .019). Conclusions. Mental silence-orientated meditation, in this case Sahaja Yoga meditation, is a safe and effective strategy for dealing with work stress and depressive feelings. The findings suggest that "thought reduction" or "mental silence" may have specific effects relevant to work stress and hence occupational health.

Neurocognitive effects of kava (Piper methysticum): a systematic review.

RATIONALE: Kava (Piper methysticum) elicits dose-dependent psychotropic effects and thus may potentially deleteriously affect cognitive performance. Clinical trials have assessed the effects of kava on cognition, however, to our knowledge no systematic review has been conducted in this area. OBJECTIVE: To systematically review the effects of kava on cognition, providing an analysis of the individual study's methodological quality, results and effect sizes. METHODS: A systematic review was conducted of publications up to June 15th 2010, using the electronic databases MEDLINE, PsychINFO, CINAHL, Web of Science and The Cochrane Library. The search criteria involved kava and cognition related terms, e.g. memory and attention. RESULTS: Ten human clinical trials met inclusion criteria (acute n = 7, chronic n = 3). One acute study found that kava significantly improved visual attention and working memory processes while another found that kava increased body sway. One chronic study found that kava significantly impaired visual attention during high-cognitive demand. Potential enhanced cognition may be attributed to the ability of kava to inhibit re-uptake of noradrenaline in the pre-frontal cortex, while increased body sway may be due to GABA pathway modulation. CONCLUSIONS: The majority of evidence suggests that kava has no replicated significant negative effects on cognition.

Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory.

AIMS: Our group has conducted several Internet investigations into the biobehavioural effects of self-reported recreational use of MDMA (3,4-methylenedioxymethamphetamine or Ecstasy) and other psychosocial drugs. Here we report a new study examining the relationship between self-reported Ecstasy use and traces of MDMA found in hair samples. METHODS: In a laboratory setting, 49 undergraduate volunteers performed an Internet-based assessment which included mood scales and the University of East London Drug Use Questionnaire, which asks for history and current drug use. They also provided a hair sample for determination of exposure to MDMA over the previous month. RESULTS: Self-report of Ecstasy use and presence in hair samples were consistent (p < 0.00001). Both subjective and objective measures predicted lower self-reported ratings of happiness and higher self-reported stress. Self-reported Ecstasy use, but not presence in hair, was also associated with decreased tension. CONCLUSION: Different psychoactive drugs can influence long-term mood and cognition in complex and dynamically interactive ways. Here we have shown a good correspondence between self-report and objective assessment of exposure to MDMA. These data suggest that the Internet has potentially high utility as a useful medium to complement traditional laboratory studies into the sequelae of recreational drug use.

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.

The effect of mobile phone electromagnetic fields on the alpha rhythm of human electroencephalogram.

Mobile phones (MP) emit low-level electromagnetic fields that have been reported to affect neural function in humans; however, demonstrations of such effects have not been conclusive. The purpose of the present study was to test one of the strongest findings in the literature; that of increased "alpha" power in response to MP-type radiation. Healthy participants (N = 120) were tested using a double-blind counterbalanced crossover design, with each receiving a 30-min Active and a 30-min Sham Exposure 1 week apart, while electroencephalogram (EEG) data were recorded. Resting alpha power (8-12 Hz) was then derived as a function of time, for periods both during and following exposure. Non-parametric analyses were employed as data could not be normalized. Previous reports of an overall alpha power enhancement during the MP exposure were confirmed (relative to Sham), with this effect larger at ipsilateral than contralateral sites over posterior regions. No overall change to alpha power was observed following exposure cessation; however, there was less alpha power contralateral to the exposure source during this period (relative to ipsilateral). Employing a strong methodology, the current findings support previous research that has reported an effect of MP exposure on EEG alpha power.

The sensitivity of human event-related potentials and reaction time to mobile phone emitted electromagnetic fields.

There is some evidence to suggest that exposure to mobile phones (MPs) can affect neural activity, particularly in response to auditory stimuli. The current investigation (n = 120) aimed to test recent findings in this area, namely that N100 amplitude and latency would decrease, and that P300 latency and reaction time (RT) would increase under active relative to sham exposure during an auditory task. Visual measures were also explored. A double blind, counterbalanced, crossover design was employed where subjects attended two sessions 1 week apart. In both sessions participants (1) performed auditory and visual oddball tasks while electroencephalogram (EEG) was recorded with a MP set to sham exposure mounted over the temporal region, and (2) performed the same tasks while the handset was set to active/sham. When active, the MP transmitted for 30 min at 895 MHz (average power 250 mW, pulse modulated at 217 Hz, average SAR 0.11 W/kg). Paired t-tests compared difference scores from the sham/sham session to those from the sham/active condition. The study was designed to detect differences of 1\4 of a standard deviation with a power of 0.80. There was no significant difference between exposure conditions for any auditory or visual event related potential (ERP) component or RT. As previous positive findings were not replicated, it was concluded that there is currently no evidence that acute MP exposure affects these indices of brain activity.

The relationship between performance on the standardised field sobriety tests, driving performance and the level of Delta9-tetrahydrocannabinol (THC) in blood.

The consumption of Delta9-tetrahydrocannabinol (THC) as cannabis has been shown to result in impaired and culpable driving. Testing drivers for the presence of THC in blood is problematic as THC and its metabolites may remain in the blood for several days following its consumption, even though the drug may no longer have an influence on driving performance. In the present study, the aim was to assess whether performance on the standardised field sobriety tests (SFSTs) provides a sensitive measure of impaired driving behaviour following the consumption of THC. In a repeated measures design, 40 participants consumed cigarettes that contained either 0% THC (placebo), 1.74% THC (low dose) or 2.93% THC (high dose). For each condition, after smoking a cigarette, participants performed the SFSTs on three occasions (5, 55 and 105 min after the smoking procedure had been completed) as well as a simulated driving test on two occasions (30 and 80 min after the smoking procedure had been completed). The results revealed that driving performance was not significantly impaired 30 min after the consumption of THC but was significantly impaired 80 min after the consumption of THC in both the low and high dose conditions. The percentage of participants whose driving performance was correctly classified as either impaired or not impaired based on the SFSTs ranged between 65.8 and 76.3%, across the two THC conditions. The results suggest that performance on the SFSTs provides a moderate predictor of driving impairment following the consumption of THC and as such, the SFSTs may provide an appropriate screening tool for authorities that wish to assess the driving capabilities of individuals suspected of being under the influence of a drug other than alcohol.

An evaluation of the sensitivity of the Standardised Field Sobriety Tests (SFSTs) to detect impairment due to marijuana intoxication.

The Standardised Field Sobriety Tests (SFST) were developed to test for alcohol intoxication but are currently being used by the State Police of Victoria (Australia) to test for driving impairment associated with drugs other than alcohol. The aim of the present study was to assess whether the SFSTs provide a sensitive measure of impairment following the consumption of a drug other than alcohol: delta-9-tetrahydrocannabinol (THC or cannabis). In a repeated-measures design, 40 participants consumed cigarettes that contained either 0% THC (placebo), 1.74% THC (low dose) or 2.93% THC (high dose). For each condition, after smoking a cigarette, participants performed the SFSTs on three occasions: 5 min (Time 1), 55 min (Time 2) and 105 min (Time 3) after the smoking procedure had been completed. The results revealed that there was a positive relationship between the dose of THC administered and the number of participants classified as impaired based on the SFSTs. Results also revealed that the percentage of participants classified as impaired decreased from Time 1 to Time 3 and that the addition of a new sign, head movements or jerks (HMJ), increased the percentage of participants classified as impaired in both the low and high THC conditions. These findings suggest that impaired performance on the SFSTs is positively related to the dose of THC administered and that the inclusion of HMJ as a scored sign in the SFSTs improves their predictive validity when testing for THC intoxication.

The effects of dexamphetamine on simulated driving performance.

RATIONALE: The number of road fatalities related to the presence of amphetamines in drivers has been relatively constant over the past 10 years. However, there remains uncertainty as to the extent that these drugs induce driving impairment, and whether any such impairments translate to an increase in road fatalities. OBJECTIVES: To examine the acute effects of 0.42 mg/kg dexamphetamine on simulated driving performance, and to establish which, if any, simulated driving abilities become impaired following dexamphetamine administration. METHODS: A repeated-measures, counter-balanced, double-blind, placebo-controlled design was employed. Twenty healthy volunteers completed two treatment conditions-0.42 mg/kg dexamphetamine and placebo. Performance was assessed using a driving simulator task. Blood and saliva samples were obtained prior to the driving tasks and immediately after task completion (120 min and 170 min post-drug administration, respectively). RESULTS: Mean dexamphetamine blood concentrations were 83 ng/ml and 98 ng/ml at 120 min and 170 min, respectively. Results indicated a decrease in overall simulated driving ability following dexamphetamine administration during the day-time but not the night-time scenario tasks. Contributing to this performance reduction, "incorrect signalling", "failing to stop at a red traffic light" and "slow reaction times" were the behaviours most strongly affected by dexamphetamine. CONCLUSIONS: The decrease in simulated driving ability observed during the day-time driving tasks are consistent with the perceptual narrowing or tunnel vision that is associated with dexamphetamine consumption.