Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults.

OBJECTIVE: Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergent neuropsychiatric symptoms (NPS) that represent an at-risk state for incident cognitive decline and dementia in people with mild cognitive impairment (MCI). We undertook a study to determine whether MBI was associated with progressive changes in neuropsychological performance in people without significant cognitive impairment. METHODS: A total of 9,931 older adults enrolled in the PROTECT study who did not have MCI or dementia undertook a comprehensive neuropsychological battery measuring attention, reasoning, executive function, and working memory at baseline and 1 year. MBI was ascertained using self-administration of the Mild Behavioral Impairment Checklist at 1 year, and participants were grouped according to MBI status: No Symptoms, Intermediate NPS and MBI. All assessments were completed online, and data analyzed using mixed-effects model repeated measures analysis of covariance. RESULTS: A total of 949 (10%) people had MBI. These individuals had significantly worse cognitive performance at baseline and significantly greater decline over 1 year in the four composite cognitive scores measuring attentional intensity (F [2,8578] = 3.97; p = 0.019), sustained attention (F [2,8578] = 18.63; p <0.0001), attentional fluctuation (F [2,8578] = 10.13; p <0.0001) and working memory (F [2,9895] = 13.1; p <0.0001). CONCLUSION: Our novel findings show that MBI is associated with faster decline in attention and working memory in this cognitively normal sample. MBI may be an earlier marker of neurodegenerative disease than MCI, captured at the stage of subjective cognitive decline or before, raising the possibility that MBI represents a novel target for dementia clinical trials or prevention strategies.

An online investigation of the relationship between the frequency of word puzzle use and cognitive function in a large sample of older adults.

OBJECTIVE: The identification of modifiable lifestyle factors to preserve cognitive function in older individuals becomes increasingly of importance. This study examines whether word puzzle use is related to cognitive function in older adults. METHODS: Cognitive data from 19 078 cognitively healthy individuals aged 50 to 93 years enrolled into the online PROTECT study were evaluated for self-reported frequency of performing word puzzles on a six-point scale, ranging from "more than once per day" to "never". Nine cognitive tests covered a range of domains including focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analyses of covariance were used to determine any differences between the six response groups. RESULTS: Each of the 14 cognitive measures analysed showed highly statistically significant main effects of the frequency of performing word puzzles. For each measure, the group who never performed word puzzles performed most poorly, with the group who reported occasional puzzle use also performing more poorly than virtually every other group. Measures of speed provided the greatest discriminations, with a grammatical reasoning score differentiating the two highest frequency groups, performing word puzzles daily or more than once daily. CONCLUSIONS: The frequency of word puzzle use is directly related to cognitive function in adults aged 50 and over. Future work needs to determine whether engaging in such puzzles can favourably influence cognitive trajectory with age.

The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over.

OBJECTIVE: Establishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number-puzzle use is related to cognitive function in older adults. METHODS: Data from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self-reported frequency of performing number puzzles. Two cognitive-test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups. RESULTS: Highly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant. CONCLUSIONS: This study has identified a close relationship between frequency of number-puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population.

Investigating the relationship between age of onset of depressive disorder and cognitive function.

OBJECTIVES: Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance. METHODS: This study examined baseline cross-sectional data from the ongoing online PROTECT study. A total of 7344 participants, 50 years or older, with a history of depression and no diagnosis of dementia were divided into three groups according to age of onset of their first depressive episode: early-onset, midlife-onset, and late-onset. Performance on measures of visuospatial episodic memory, executive function, verbal working, and visual working memory were evaluated. Demographic and clinical characteristics such as age, education, and severity of symptoms during their worst previous depressive episode and current depression severity were included in multivariate regression models. RESULTS: The late-onset depression group scored significantly lower on the verbal reasoning task than the early-onset group while there were no significant differences found on the other tasks. Midlife-onset depression participants performed better in the visual episodic memory task, but worse on the verbal reasoning task, than early-onset depression participants. Current depression severity was negatively correlated with all four cognitive domains, while historical severity score was found to be significantly associated with cognitive performance on the verbal reasoning and spatial working memory tasks. CONCLUSIONS: The most important indicator of cognitive performance in depression appears to be current, rather than historic depression severity; however, late-onset depression may be associated with more executive impairment than an early-onset depression.

The effects of the selective muscarinic M3 receptor antagonist darifenacin, and of hyoscine (scopolamine), on motion sickness, skin conductance & cognitive function.

AIMS: The aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist darifenacin, oral hyoscine hydrobromide and placebo on motion sickness induced by cross-coupled stimulation. METHODS: The effects of darifenacin 10 mg or 20 mg, hyoscine hydrobromide 0.6 mg and placebo were assessed in a randomized, double-blind, four-way cross over trial of 16 healthy subjects. Motion sickness, skin conductance (a measure of sweating) and psychomotor cognitive function tests were investigated. RESULTS: Hyoscine hydrobromide produced significantly increased tolerance to motion versus placebo (P < 0.05 to P < 0.01). The motion protection effect of darifenacin (10 or 20 mg) was approximately one third that of hyoscine hydrobromide but was not significant versus placebo. Darifenacin and hyoscine hydrobromide both significantly reduced skin conductance versus placebo. Darifenacin produced either no effect or an enhanced effect on cognitive function in contrast to hyoscine hydrobromide, where there was significant impairment of psychomotor performance. CONCLUSION: The results suggest that selective antagonism of the M3 receptor may not be important in the prevention of motion sickness. However, selective M3 antagonism does not impair cognitive function. These observations may be important given that long-term treatment with non-selective anti-muscarinic agents such as oxybutynin may lead to an increased incidence of dementia.

Longitudinal changes in global and domain specific cognitive function in the very-old: findings from the Newcastle 85+ Study.

OBJECTIVE: Ageing is associated with changes in cognition in some, but not all domains. In young-old adults, defined as persons aged 65-84 years, baseline cognitive function has been shown to impact on cognitive trajectories. Whether similar patterns occur in the very-old, defined as persons aged 85 years and over, is not known. METHODS: Longitudinal changes (5 years' follow-up) in global and domain specific cognitive function including memory, attention and speed were investigated in participants from the Newcastle 85+ Study (n = 845). At baseline, participants were grouped using Mini-Mental State Examination cut-off scores and dementia status into the following: not impaired, mildly impaired or severely impaired/dementia groups. RESULTS: Only a limited number of cognitive measures showed significant decline in performance over time. Where observed, change generally occurred only in the severely impaired group. In the severely impaired group, small differences in baseline age were associated with poorer performance over time on most measures. Education was not protective against cognitive decline in any group. CONCLUSIONS: There are individuals who maintain a high level of cognitive function or only show mild impairments even into their ninth decade of life. This group of successful cognitive agers may provide insight for identifying predictors of cognitive integrity in later life. In individuals with severe impairment, cognitive performance shows significant decline over time, especially in measures of attention and speed. Further work to identify those individuals at highest risk of cognitive decline is necessary to implement early support and intervention strategies in this rapidly expanding age group. © 2017 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Utility, reliability, sensitivity and validity of an online test system designed to monitor changes in cognitive function in clinical trials.

OBJECTIVE: The advent of long-term remotely conducted clinical trials requires assessments which can be administered online. This paper considers the utility, reliability, sensitivity and validity of an internet-based system for measuring changes in cognitive function which is being used in one such trial. METHODS: The Platform for Research Online to investigate Genetics and Cognition in Ageing is a 10-year longitudinal and entirely remote study launched in November 2015. The CogTrackTM System is being used to monitor changes in important aspects of cognitive function using tests of attention, information processing and episodic memory. On study entry, the participants performed CogTrackTM up to three times over seven days, and these data are evaluated in this paper. RESULTS: During the first six months of the study, 14 531 individuals aged 50 to 94 years enrolled and performed the CogTrackTM System, 8627 of whom completed three test sessions. On the first administration, 99.4% of the study tasks were successfully completed. Repeated testing showed training/familiarisation effects on four of the ten measures which had largely stabilised by the third test session. The factor structure of the various measures was found to be robust. Evaluation of the influence of age identified clinically relevant declines over the age range of the population on one or more measures from all tasks. CONCLUSIONS: The results of these analyses identify CogTrackTM to be a practical and valid method to reliably, sensitively, remotely and repeatedly collect cognitive data from large samples of individuals aged 50 and over. Copyright © 2017 John Wiley & Sons, Ltd.

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients.

BACKGROUND: The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. METHODS AND RESULTS: Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (ß = -0.34 vs ß = -0.35) were significant predictors of attention, and CCA-BFV (ß = -0.34) was a predictor of executive function. CONCLUSIONS: Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients.

Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial.

OBJECTIVE: Assess cognitive effects of adjunctive perampanel in adolescents. METHODS: In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1-3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8-12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT). RESULTS: One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, -0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (-6.9 vs. -2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. -1.2; p = 0.012), and worsening in Continuity of Attention (-3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%). SIGNIFICANCE: Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain.

Single-Dose Interaction Study of the Arginine Vasopressin Type 1B Receptor Antagonist ABT-436 and Alcohol in Moderate Alcohol Drinkers.

BACKGROUND: ABT-436, a potent and selective arginine vasopressin (AVP) type 1B receptor (V1B ) antagonist, has previously demonstrated basal hypothalamic-pituitary-adrenal (HPA) axis attenuation in man. A V1B antagonist is hypothesized as an alcohol-dependent treatment based on the role of the V1B receptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V1B antagonist has shown favorable effects in rat models of alcohol dependence. A single-dose clinical study was conducted to assess the potential for pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol. METHODS: Twenty moderate alcohol drinkers each received the 4 possible combinations of a single 1,000 mg ABT-436 dose (or matching placebo) and a single 0.5 g/kg alcohol dose (or placebo for alcohol) in a double-blind, randomized, 4-period crossover study. Plasma ABT-436 and blood alcohol levels were measured to assess pharmacokinetic interactions. A computerized cognitive test battery (CDR System), Bond-Lader Visual Analog Scales scales, and a postural stability test were used to measure the effects of alcohol and the potential interaction with ABT-436. The pharmacologic effect of ABT-436 was assessed by measuring serum cortisol. RESULTS: Neither ABT-436 nor alcohol affected the blood levels of the other. Alcohol reduced performance on 2 of 5 CDR System composite variables (power of attention, p = 0.002; quality of secondary episodic memory, p < 0.001), and decreased postural stability (p = 0.043). ABT-436 did not exacerbate those deleterious effects. ABT-436 reduced serum cortisol (p < 0.001), and alcohol did not significantly diminish this expected effect on the HPA axis. CONCLUSIONS: No pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol was observed.

Differences in memory function between 5-HT1A receptor genotypes in patients with major depressive disorder.

BACKGROUND: While extensive literature on the role of the serotonin receptor 1A (5-HT1A-R) in cognition exists, the findings are largely from animal studies. There has been little research conducted into 5-HT1A-R genotypes and cognitive function in humans. This article evaluates the role of 5-HT1A-R genotypes on the profile of cognitive function in patients with major depressive disorder (MDD). METHODS: The study sample was 455 MDD patients aged between 18 and 55 years. They had enrolled into a clinical trial and were tested prior to dosing on the baseline study day using the CDR System, an integrated set of 3 attention tests, 2 working memory tests, and 4 episodic memory tests. 5-HT1A-R genotyping for (SNP ID rs6295) had been conducted during the study screening period. RESULTS: Validated factor scores were derived from the 9 tests. It was found that patients with the C/C genotype for the C(1019)G polymorphism of the 5-HT1A-R were significantly superior in retaining and retrieving information, in both working and episodic memory, than those with either the C/G or the G/G genotypes. No differences were found in measures of attention or in the speed of retrieval of information from memory. CONCLUSIONS: This is, to our knowledge, the first relationship found between objective tests of cognitive function and 5-HT1A-R genotypes in MDD.

Memantine improves attention and episodic memory in Parkinson's disease dementia and dementia with Lewy bodies.

OBJECTIVE: In both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), attentional dysfunction is a core clinical feature together with disrupted episodic memory. This study evaluated the cognitive effects of memantine in DLB and PDD using automated tests of attention and episodic memory. METHODS: A randomised double-blind, placebo-controlled, 24-week three centre trial of memantine (20 mg/day) was conducted in which tests of attention (simple and choice reaction time) and word recognition (immediate and delayed) from the CDR System were administered prior to dosing and again at 12 and 24 weeks. Although other results from this study have been published, the data from the CDR System tests were not included and are presented here for the first time. RESULTS: Data were available for 51 patients (21 DLB and 30 PDD). In both populations, memantine produced statistically significant medium to large effect sized improvements to choice reaction time, immediate and delayed word recognition. CONCLUSIONS: These are the first substantial improvements on cognitive tests of attention and episodic recognition memory identified with memantine in either DLB or PDD.

Improved working memory performance following administration of a single dose of American ginseng (Panax quinquefolius L.) to healthy middle-age adults.

OBJECTIVE: A ginsenoside-rich extract of American ginseng (Panax quinquefolius L.), Cereboost(TM), was previously shown to improve working memory and mood in healthy young individuals. The present study represented a partial replication investigating whether these effects extended to healthy middle-aged individuals. METHODS: Fifty-two healthy volunteers (40-60 years old, mean age 51.63) received 200 mg of P. quinquefolius or a matching placebo according to a double-blind, placebo-controlled, balanced, crossover design. The Cognitive Drug Research battery and the Computerised Mental Performance Assessment System were used to evaluate cognitive performance at baseline then 1, 3 and 6 h following treatment. Blood glucose and mood were co-monitored. RESULTS: Compared with placebo, P. quinquefolius improved cognitive performance on 'Working Memory' factor at 3 h. Similar effects were observed in one of the two tasks making up this factor, spatial working memory. There were no significant effects on mood or blood glucose levels. CONCLUSIONS: These data confirm that P. quinquefolius can acutely benefit working memory and extend the age range of this effect to middle-aged individuals. These changes are unlikely to be underpinned by modulation of blood glucose in this population.

Atomoxetine for attention deficits following traumatic brain injury: results from a randomized controlled trial.

OBJECTIVE: To determine if atomoxetine would improve attention impairment following traumatic brain injury (TBI). SETTING: Outpatients from a free-standing, private, not-for-profit rehabilitation hospital. POPULATION: Fifty-five adult participants with a history of a single moderate-to-severe TBI, who were at least 1 year from injury and with self-reported complaints of attention difficulties. INTERVENTION: Atomoxetine, a selective norepinephrine re-uptake inhibitor with a primary indication for attention dosed at 40 mg twice a day for 2 weeks, compared to placebo. DESIGN: Randomized double-blind placebo controlled trial, with placebo run-in. MEASURES: Cognitive Drug Research (CDR), Computerized Cognitive Assessment System, Stroop Color and Word Test, Adult ADHD Self-Report Scale (ASRS-v1.1), Neurobehavioural Functioning Inventory (NFI). RESULTS: Atomoxetine was well-tolerated by the subject sample. The use of atomoxetine by individuals with reported attention difficulty following TBI did not significantly improve scores on measures of attention, the CDR Power of Attention domain or the Stroop Interference score. In addition, no significant relationship was found between atomoxetine use and self-reported symptoms of attention or depression. CONCLUSION: Atomoxetine did not significantly improve performance on measures of attention among individuals post-TBI with difficulties with attention. This study follows a trend of other pharmacological studies not demonstrating significant results among those with a history of TBI. Various possibilities are discussed, including the need for a more sophisticated system of classification of TBI.

Examining the cognitive effects of a special extract of Bacopa monniera (CDRI08: Keenmnd): a review of ten years of research at Swinburne University.

Bacopa monniera (EBm), an Indian aquatic herb, has been used in traditional Ayurvedic medicine for centuries for indications related to memory and inflammation. More recently specific extracts of EBm have emerged that have been subjected to rigorous in vitro, animal and now human clinical trials. In this paper we discuss some of these studies with special reference to mechanisms and efficacy of a special extract of Bacopa (CDRI08). Studies using this extract indicate that CDRI08 has several modes of action on the human brain. Promising indications for use in humans include improving cognition in the elderly and in patients with neurodegenerative disorders.

An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-blind, placebo controlled, cross-over study.

Energy drinks are widely available mostly containing glucose, and several have been demonstrated to improve alertness and cognitive function; these effects generally being identified 30-60min after administration. The present study assessed whether an energy shot without carbohydrates would affect major aspects of cognitive function and also mood in volunteers over a 6h time period. This randomized, double-blind, placebo-controlled,crossover study compared the acute effects of the energy shot with a matching placebo in 94 healthy volunteers. Cognitive function was assessed with a widely used set of automated tests of attention and memory. Mood was assessed with the Bond-Lader, Beck Anxiety Index, Beck Depression Index, Chalder Fatigue Scales (CFS), and the POMS. The volunteers were requested to limit their sleep to between 3 and 6h the night before each testing day. Compared to the placebo, the energy shot significantly improved 6 validated composite cognitive function measures from the CDR System as well as self-rated alertness; the benefits on 4 of the cognitive measures still remaining at 6h. The overall effect sizes of the performance improvements were in the small to medium range and thus notable in this field. In conclusion, an energy shot can significantly improve important aspects of cognitive function for up to 6h compared to placebo in partially sleep-deprived healthy volunteers.

Relationship between cognition, magnetic resonance white matter hyperintensities, and cardiovascular autonomic changes in late-life depression.

OBJECTIVES: To explore the relationship between specific aspects of cognition, white matter hyperintensities (WMHs), and cardiovascular autonomic parameters in late-life depression (LLD). DESIGN: Cross-sectional analysis. SETTING: Secondary care psychiatry. PARTICIPANTS: Forty-one individuals older than 60 years, with current or previous history of major depression, and 32 age-matched comparison subjects. MEASUREMENTS: Cognition was assessed by a standardized computer battery of tasks (Cognitive Drug Research) that measured processing speed, attention, episodic memory, and working memory. Cardiovascular autonomic parameters were estimated by a noninvasive device that calculated blood pressure, heart rate variability, and baroreflex sensitivity (Task Force Monitor). Magnetic resonance imaging was performed on a 3-T magnetic resonance imaging system, and WMH volume was estimated using an automated validated method. RESULTS: As expected, cognitive deficits in all tested domains were present in LLD subjects compared with comparison subjects. In the LLD group, processing speed was correlated with scores on memory and working memory tasks. Attentional deficits were correlated with total and periventricular WMH volume, and episodic memory was associated with heart rate variability. There were no associations between cognitive variables and traditional vascular risk factors or between cognitive variables and any of these parameters in the comparison subjects. CONCLUSIONS: This study suggests that processing speed may be an important factor underlying deficits in LLD, but it also indicates that other factors, including those related to vascular disease, are important and thus provide further support for the vascular depression hypothesis.

The cognitive profile of type 1 Gaucher disease patients.

BACKGROUND: The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well. METHODS: Cognitive function was assessed in a large cohort of GD1 patients with the use of the CDR system, a set of computerised cognitive tests. Testing was performed at baseline and every 6 months thereafter during a two-year study period. RESULTS: Our patient cohort (84 patients, median age 40 years, median time from diagnosis 15 years) showed mild deficits relative to healthy age-matched subjects on the composite scores: power of attention (Z-score (mean ± SD) -0.9 ± 1.37) and speed of memory (Z-score (mean ± SD) -1.39 ± 1.49). No decline in cognitive function was seen during the two-year period. Age correlated with the composite scores variability of attention and quality of working memory. Moreover, severely affected patients (Zimran severity score (SSI) ≥ 15) scored more poorly compared to mildly affected patients (SSI ≤ 5) on the composite measure power of attention, reflecting the ability to concentrate. CONCLUSIONS: GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory. The clinical relevance of these findings is uncertain.

Analysis of neuron-specific enolase and S100B as biomarkers of cognitive decline following surgery in older people.

BACKGROUND/AIMS: Post-operative cognitive decline is frequent in older individuals following major surgery; however, biomarkers of this decline are less clearly defined. METHODS: Sixty-eight participants over the age of 60 provided blood samples at baseline and 24 h post-surgery. Cognitive decline was measured at baseline and 52 weeks post-surgery using the Cambridge Assessment for Mental Disorder in the Elderly, section B (CAMCOG) score. Plasma levels of neuron-specific enolase (NSE) and S100B were measured by ELISA. RESULTS: Baseline NSE and the change in NSE levels between baseline and 24 h were correlated with the change in CAMCOG score between baseline and 52 weeks. CONCLUSION: NSE concentrations may be a useful predictor of individuals at risk of more severe long-term cognitive decline.

A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910).

BACKGROUND: One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. METHODS: In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI) was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day), Pycnogenol (150 mg/day), or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation, oxidative stress and safety) as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms). The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration.ARCLI will represent one of the largest and most comprehensive experimental clinical trials in which supplements are administered to elderly participants. Results from ARCLI may help develop novel preventative health practices and nutritional/pharmacological targets in the elderly for cognitive and brain health. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487910.