Cambridge Brain Sciences Research Articles

Maintain Your Brain: outcomes of an online program to prevent cognitive decline with aging.

AbstractBackgroundEfforts to prevent cognitive decline with aging have had mixed results with successful interventions delivered in person. While online approaches are more scalable and feasible to deliver at a population level, no multimodal online intervention has yet been demonstrated efficacy. We aimed to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months.MethodInvitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). Participants were required to be eligible for at least two of four modules addressing physical inactivity and associated health risks (Physical Activity), adherence to a Mediterranean‐type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well‐being (Peace of Mind). Participants received modules based on their risks, with 1:1 randomized allocation to active personalised coaching modules (intervention) or static information‐based modules (control). The primary outcome was change in an online combined multi‐domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests. Secondary outcomes included specific cognitive domain and ANU‐ADRI risk scores.ResultOf 96,418 invitations issued, 14,064 (14%) consented, 11,026 (11%) were eligible and 6,104 (6%) completed all baseline assessments. Over three years, using intention to treat analysis, the intervention group improved significantly more in the global composite cognition (p<0.001). Significant benefits were also found in complex attention, executive function and learning and memory (all p<0.001), as well as on a validated dementia risk instrument (p = 0.007). Results were similar when adjusted for baseline age, gender, dementia risk and number of modules eligible and when analysis was based on those completing follow‐up.ConclusionAn online platform tailored to individuals’ risk factor profiles over three years significantly delayed cognitive decline in older adults. This platform is scalable; if delivered at a population level with may help reduce the prevalence of dementia globally.

Poorer online cognitive performance is associated with genetic risk for Alzheimer’s disease and brain phenotypes in healthy mid‐life and older adults.

AbstractBackgroundSelf‐administered online cognitive testing offers a cost‐effective and flexible alternative to in‐person neuropsychological assessments. We used the Creyos platform (previously named Cambridge Brain Sciences) to assess cognitive function in a large sample (N = 1673) of middle aged and older adults participating in the PISA (Prospective Imaging Study of Aging) study. PISA aims to characterise the early symptoms and progression of Alzheimer’s disease at its prodromal phase.MethodWe have utilised our Australia‐wide population based sample recruitment pool of research participants with genome wide genotyping. Participants completed a comprehensive online survey and online cognitive assessments, including Creyos, consisting of 12 self‐administered tasks covering memory, executive function, language, and visuo‐spatial domains. Using genetic profile scores in a sample size of 1,673 (70% female, aged 42‐75 years, mean 60.8). We tested the association between cognitive test results and genetic risk for Alzheimer’s disease and related phenotypes including structural neuroimaging measures.ResultsOur findings indicate a significant association of Alzheimer’s polygenic risk scores (PRS) with cognitive test results in healthy individuals within memory and executive function domains. The results of analyses with additional genetic profile scores including psychiatric traits and structural neuroimaging measures will also be presented.ConclusionThose who are at high genetic risk for Alzheimer’s disease have reduced cognitive function prior to dementia diagnosis from middle age. Our results highlight the utility of online cognitive testing as a cost‐effective alternative to in person testing for large scale studies and the potential for it’s used as a pre‐screening approach to identify those at high risk of Alzheimer’s disease.

FC4: Maintain Your Brain: a scalable 3-year online intervention which reduced cognitive decline in 55-77 year olds

Objective:There is increasing focus on effective preventative interventions applicable at the population scale such as through technology and web-based approaches. We aimed to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months.Methods:Invitations were sent to people aged 55-77 years from the 45 and Up study, a population-based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n=267,000). Participants were required to be eligible for at least two of four modules addressing physical inactivity and associated health risks (Physical Activity), adherence to a Mediterranean-type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well-being (Peace of Mind). Participants received modules based on their risks, with 1:1 randomized allocation to active personalised coaching modules (intervention) or static information-based modules (control). The primary outcome was change in an online combined multi-domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests using intention to treat analysis. Secondary outcomes included specific cognitive domain and ANU-ADRI risk scores.Results:From 96,418 invitations, 14,064 (14%) consented; 11,026 (11%) were eligible; and 6,104 (6%) completed all 10 baseline assessments. Over three years there was a significantly greater improvement in the global composite cognition z-score in the intervention group, ES = 0.106 (p<0.001). Significant benefits were also found in complex attention, executive function and learning and memory (all p<0.001), as well as on a validated dementia risk instrument (p=0.007).Conclusion:An online platform that tailored physical activity, nutrition, brain training, depression and anxiety interventions to an individual’s risk factor profile over three years significantly delayed cognitive decline in older adults. This platform is scalable and if rolled out at a population level may help reduce the prevalence of dementia globally.

The Brain Balance® programme improves attention and classroom behaviour in students with attentional and developmental challenges in a school setting (El programa Brain Balance® mejora la atención y el comportamiento en el aula de estudiantes con dificultades de atención y de desarrollo en un entorno escolar)

ABSTRACT The Brain Balance® (BB) programme has been examined in a centre-based setting, but not yet in a school setting. This pilot study assessed sensorimotor, behavioural and cognitive functioning of students aged 5–15 years with pre-existing developmental and academic challenges who attended three one-hour sessions/week of the BB programme on-site at school (n = 15). Non-participating students served as controls (CTLs; n = 11). Before the programme, BB participants were more likely than CTLs to achieve low scores on at least two of six Cambridge Brain Sciences (CBS) cognitive tests. After the programme, the number of these participants with low scores decreased, compared with CTLs. Following participation, the BB group also demonstrated diminished primitive reflexes and improvement in scores on the Vanderbilt ADHD Diagnostic Teacher Rating Scale (VADTRS), and higher scores on sensorimotor tasks, compared with CTLs. Finally, BB participants tended to improve test accuracy and reaction times on six CBS cognitive tests (non-significant). These preliminary results show the potential efficacy of the BB programme in a school setting. Future studies will assess the programme in larger student populations.

Effects of Increasing Indoor Negative Air Ions on Cognitive Performance and Health of High Pure CO2 Level-Exposed College Students

Cognitive performance is essential to foster learning. High CO2 concentrations are common in classrooms and can lead to reduced cognitive performance. Negative air ions (NAIs) can improve cognitive performance. This study explored the effects of indoor NAIs on the cognitive performance and health of college students exposed to a high pure CO2 environment. Forty college students were exposed to four sets of conditions (NAIs+500 ppm CO2, 500 ppm CO2, NAIs+2500 ppm CO2, and 2500 ppm CO2). Participants’ cognitive performance, including reasoning, short-term memory, concentration, and verbal ability, was assessed under each condition using the Cambridge Brain Sciences tool. Acute health symptoms were investigated using a subjective questionnaire, and simultaneously, participants’ blood pressure, heart rate, and lung function were tested. Analysis of variance (ANOVA) in a repeated-measures design was used to analyze the effects of different conditions on cognitive performance and health symptoms. The results revealed that the different levels of CO2 and NAIs had a significant effect on cognitive performance after one hour of exposure and had no significant effect after three hours of exposure. Compared with 500 ppm CO2, 500 ppm CO2+NAIs resulted in better reasoning skills, short-term memory, and verbal skills, and 2500 ppm CO2 led to poorer reasoning skills. The addition of NAIs to 2500 ppm CO2 improved reasoning skills, short-term memory, and verbal skills. The benefits of adding NAIs to high pure CO2 condition on cognitive performance are more noticeable than those to low CO2 condition. Moreover, adding NAIs can reduce nasal irritation or dryness, skin irritation or dryness, sleepiness symptoms, and heart rate elevation caused by pure CO2. However, the benefits of NAIs on health symptoms and physiology were not observed under the 500 ppm CO2 condition. Adding NAIs to a high pure CO2 level is an effective means to improve the cognitive performance and health of college students.

Reliability, Validity, and User-Experience of Remote Unsupervised Computerized Neuropsychological Assessments in Community-Living 55- to 75-Year-Olds.

Self-administered computerized neuropsychological assessments (CNAs) provide lower cost, more accessible alternatives to traditional in-person assessments but lack critical information on psychometrics and subjective experience of older adults in remote testing environments. We used an online brief battery of computerized tasks selected from the Cogstate Brief Battery (CBB) and Cambridge Brain Sciences (CBS) to 1) determine test-retest reliability in an unsupervised setting; 2) examine convergent validity with a comprehensive 'gold standard' paper-and-pencil neuropsychological test battery administered in-person; and 3) explore user-experience of remote computerized testing and individual tests. Fifty-two participants (mean age 65.8±5.7 years) completed CBB and CBS tests on their own computer, unsupervised from home, on three occasions, and visited a research center for an in-person paper-and-pencil assessment. They also completed a user-experience questionnaire. Test-retest reliabilities varied for individual measures (ICCs = 0.20 to 0.83). Global cognition composites showed excellent reliability (ICCs > 0.8 over 1-month follow-up). A strong relationship between a combination of CNA measures and paper-and-pencil battery was found (canonical correlation R = 0.87, p = 0.04). Most tests were rated as enjoyable with easy-to-understand instructions. Ratings of general experience with online testing were mostly favorable; few had difficulty concentrating (17%) or using the computer for tasks (10%), although over one-third experienced performance anxiety (38%). A combined brief online battery selected from two CNAs demonstrated robust psychometric standards for reliability (global composite), and convergent validity with a gold standard battery, and mostly good usability and acceptability in the remote testing environment.

Computer‐administered neuropsychological assessment batteries: Validity, reliability, and user experience in an Australian sample of community‐living older adults in the CogSCAN Study

AbstractBackgroundAccess to a “gold‐standard” in‐person neuropsychological assessment to detect cognitive decline in older adults using paper‐and‐pencil (PnP) tests is limited. Computerized neuropsychological assessments (CNAs) potentially provide lower cost, scalable, accessible alternatives but critical psychometric data on the validity, reliability and user‐experience of CNAs in older adults are lacking.Method263 community‐dwelling individuals aged 60 years and older without dementia were assigned to complete two CNA batteries and one standardised neuropsychological assessment with 14 PnP tests, one week apart (Construct Validity Group) or two CNAs on two occasions, one month apart (Reliability Group). CNAs were self‐administered under supervision. Orders of CNA batteries, and of CNA and PnP sessions were counterbalanced (Figure 1). Participants completed questionnaires evaluating their experience after each CNA battery. Four CNA batteries were investigated: Cambridge Brain Sciences (CBS), CANTAB, Cogstate, and NIH Toolbox, each containing 5—8 tests; key variables recommended by the test developers were examined (Table 1).ResultParticipant characteristics are summarised in Table 2. Concurrent Validity: Modest correlations (r’s of 0.3‐0.6) between CNA and PnP measures were observed for all CNA batteries, generally aligning with corresponding domains, though notably reflecting the multidimensionality of cognitive measures (Table 3); the strongest associations (r ≥0.5) were with attention and processing speed measures across three CNA batteries, also NIH Toolbox vocabulary, memory and executive measures.Reliability: One‐month test‐retest reliabilities of individual measures were variable (Table 4); across three batteries some, typically speed measures, had reliability coefficients ≥ 0.7. User Experience: Completion rates were high (96‐100%). Usability ratings of CNAs were high on average, although variability was large for CBS (Figure 2). Ratings of acceptability were lower than usability, though on average, participants endorsed CNAs positively.ConclusionA selection of computerized measures demonstrated adequate psychometric standards for concurrent validity with ‘gold standard’ in‐person neuropsychological assessments, alongside good usability and acceptability, though test‐retest reliability was low for many measures. CogSCAN’s comprehensive comparative data will guide researchers in selecting the most suitable CNA measures for older adults. Work in progress is investigating CNA validity, reliability and user experience in older adults with cognitive decline and culturally and linguistically diverse older adults.

Maintain Your Brain: a 3‐year online randomized controlled trial to reduce cognitive decline in 55‐77 year olds

AbstractBackgroundTechnology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia such as physical inactivity, suboptimal nutrition and low cognitive activity. Our aim was to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months. The trial was completed in November 2021.MethodInvitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). Participants were required to be eligible for at least two of four modules. The modules addressed physical inactivity and health risks associated with inactivity (Physical Activity), adherence to a Mediterranean‐type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well‐being (Peace of Mind). All participants received modules based on their risks, with randomized allocation to active personalised coaching modules (intervention) or static information‐based modules (control). The primary outcome was change in an online combined multi‐domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests. Secondary outcomes included ANU‐ADRI risk score, specific cognitive domain scores and diagnoses of dementia.ResultFrom 96,418 invitations, 14,064 (14%) consented; 12,281 (13%) were eligible. Of these, 6,236 (6%) completed all 10 baseline assessments and were enrolled in the trial. Nearly 70% or 4,365 participants provided follow‐up data. At final 36‐months’ follow‐up, 3,482 (55.8%) completed the primary outcome and 2594 (41.6%) had returned informant‐rated Amsterdam‐Instrumental Activities of Daily Living Scale questionnaires.ConclusionOnline strategies to prevent cognitive decline in 55‐77 year olds are feasible and appear acceptable for more than half of participants. Analysis of group*time effects will be presented.

Effects of a Bonded Arginine Silicate Inositol combination (nooLVL®) on Cognitive function in esports Gamers

ObjectivesThe purpose of this open‐label study was to assess the ability of a bonded arginine silicate inositol combination (nooLVL) to affect reaction time and responses to cognitive tasks in esports gamers. nooLVL is a non‐stimulant complex of bonded arginine silicate with inositol. Previous studies have evaluated nooLVL in esports gamers showing improvements in accuracy, decision making, and reaction time during gaming. This study looks to further detect cognitive changes in esports gamers on an array of cognitive tests developed by Cambridge Brain Sciences.MethodsAssessments were evaluated on six Cambridge Brain Sciences (CBS) cognitive tasks: Feature Match, Double Trouble, Mental Rotations, Polygons, Odd One Out, and Spatial Planning. These tests measure visuospatial processing, deductive reasoning, intelligent behavior, concentration, and attention. The subjects were healthy adult males and females (age >18; n=9) with minimum previous gaming experience of 3‐5 hours of video games per week for at least 6 months. All study participants consumed 1600mg per day of nooLVL (600mg arginine, 105mg silicon, 385mg inositol and 60mg potassium) for seven days. They completed the CBS tests at baseline, on day 1 after a single dose of nooLVL, and again on day 7.ResultsMean changes within group at baseline to day 1, day 1 to day 7 and baseline to day 7 were analyzed with paired t‐tests. Significant differences were found in Double Trouble (baseline vs day 1 [p=0.0019], day 1 vs day 7 [p=0.0369] and baseline vs day 7 [p=0.0005]), Mental Rotations (baseline to day 1 [p=0.0506] and baseline to day 7 [p=0.0192]), and Spatial Planning (baseline to day 7 was observed [p=0.0266]). The Double Trouble assessment measures concentration, Mental Rotations examination measures the function of visual representation in the brain, and Spatial Planning assessment measures intelligent behavior through forethought and sequencing performance.Outcomes of the Feature Match, Polygons, and Odd One Out tests did not show significance.ConclusionsThese data show that nooLVL® a complex of bonded arginine silicate with inositol, when used in esport gamers, improves outcomes on certain functioning tests such as visual processing, concentration, and spatial learning as early as after a single dose and lasting up to seven days.

The use of online testing to assess cognitive differences in healthy individuals at high genetic risk of Alzheimer's disease.

The PISA study aims to characterise the natural history and symptom progression of Alzheimer's disease (AD) at its prodromal phase. Utilising genetic risk prediction we have identified middle-aged and older Australians at high risk of dementia. In addition to onsite phenotyping, online surveys and cognitive testing have been used to economically collect information from an Australia-wide sample. We have utilised our population based sample recruitment pool (N=15,351) of previous research participants who have been genome wide genotyped. Participants are invited to complete a comprehensive online survey, then complete online cognitive assessments, including Cambridge Brain Sciences (CBS), Cogstate, and an emotion recognition task. Thus far nearly 4,000 participants have taken part in our online survey, and of these 2055 participants have completed the CBS assessment consisting of twelve subtests assessing memory, reasoning, attention, and planning. Recruitment for CBS and the other platforms is ongoing and participants are being invited to complete follow-up assessments after two years. At baseline we find significant association of both APOE genotype and polygenetic risk scores (PRS) for AD (omitting the APOE region) in healthy middle aged and elderly individuals with cognitive domains tested using the CBS platform. The utility of online cognitive testing for large scale testing in cohort and epidemiological studies will be discussed. The identification of cognitive changes associated with AD risk and prodromal disease gives important insights into mechanisms of AD development throughout the life span and is an opportunity to investigate prodromal markers to allow selection of individuals for early treatment strategies.

Cognition and elevated blood pressure in community‐dwelling older adults with subjective cognitive decline: A cross‐sectional exploratory study

AbstractBackgroundThe impact of blood pressure (BP) on cognition in older adults remains equivocal. We investigated the relationships between cognition (global and domain‐specific) and ambulatory blood pressure in older adults with subjective cognitive decline (SCD).MethodWe conducted a cross‐sectional exploratory analysis of data collected from 230 community‐dwelling older adults (age mean [SD]: 69.3 [7.2], 57.8% female) with self‐reported SCD. We assessed global cognitive functioning, memory, concentration, planning, and reasoning using the computer‐based Cambridge Brain Sciences battery. Assessment of 24‐hour BP was performed using an automated, ambulatory BP monitoring device (SpacelabsModel 90207). Ambulatory BP was measured every 30 minutes between 6am and 10pm, and hourly between 10pm and 6am. We employed hierarchical regression models to examine associations between 24‐hour systolic BP and cognition. Further, we conducted ANCOVAs exploring dose‐response relationships by stratifying our sample using clinical cut‐offs for normal (≤120 mmHg, n = 52), preclinical (121 to 135 mmHg, n = 119), and hypertensive (>135 mmHg, n = 59) BP. All analyses were adjusted for age, sex, MoCA, years of education, and diagnosis of diabetes and/or hypertension.ResultIn our sample, 24‐hour systolic BP was negatively associated with reasoning scores (unstandardized B [95% CI] = ‐0.008 [‐0.016 to ‐0.001], R2Change = 0.016, p = 0.028). The dose‐response analysis revealed a main group effect (F[2,221] = 3.6, p = 0.029, ηp2= 0.032), with post‐hocpairwise comparisons indicating that individuals with normal BP levels outperformed those with preclinical (mean difference [95% CI] = 0.280 [0.068 to 0.492], p = 0.010), and hypertensive (0.265 [0.021 to 0.508], p = 0.034) BP levels. The tasks adopted to assess reasoning targeted specifically grammatical reasoning, conflict resolution, and deductive reasoning, which fall under the overall scope of executive function tasks. No other relevant associations or interactions were found.ConclusionIn this sample of older adults with SCD, 24‐hour systolic BP levels above optimal clinical parameters were negatively associated with cognitive reasoning performance. Future research should investigate whether interventions that target BP control could mitigate impairment on reasoning performance.

The factor structure of executive function in childhood and adolescence

Executive functioning (EF) plays a major role in many domains of human behaviour, including self-regulation, academic achievement, and even sports expertise. While a significant proportion of cross-sectional research has focused on the developmental pathways of EF, the existing literature is fractionated due to a wide range of methodologies applied to narrow age ranges, impeding comparison across a broad range of age groups. The current study used a cross-sectional design to investigate the factor structure of EF within late childhood and adolescence. A total of 2166 Flemish children and adolescents completed seven tasks of the Cambridge Brain Sciences test battery. Based on the existing literature, a Confirmatory Factor Analysis was performed, which indicated that a unitary factor model provides the best fit for the youngest age group (7–12 years). For the adolescents (12–18 years), the factor structure consists of four different components, including working memory, shifting, inhibition and planning. With regard to differences between early (12–15 years) and late (15–18 years) adolescents, working memory, inhibition and planning show higher scores for the late adolescents, while there was no difference on shifting. The current study is one of the first to administer the same seven EF tests in a considerably large sample of children and adolescents, and as such contributes to the understanding of the developmental trends in EF. Future studies, especially with longitudinal designs, are encouraged to further increase the knowledge concerning the factor structure of EF, and the development of the different EF components.

Effects of Inositol-Enhanced Bonded Arginine Silicate Ingestion on Cognitive and Executive Function in Gamers.

Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7–14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.

Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

ABSTRACTBackgroundSupplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations.ObjectiveThe objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI).MethodsA total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons.ResultsA total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052).ConclusionsDietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. This trial was registered at clinicaltrials.gov as NCT03369925.

Protocol for the Prognostication of Consciousness Recovery Following a Brain Injury.

Individuals who have suffered a severe brain injury typically require extensive hospitalization in intensive care units (ICUs), where critical treatment decisions are made to maximize their likelihood of recovering consciousness and cognitive function. These treatment decisions can be difficult when the neurological assessment of the patient is limited by unreliable behavioral responses. Reliable objective and quantifiable markers are lacking and there is both (1) a poor understanding of the mechanisms underlying the brain’s ability to reconstitute consciousness and cognition after an injury and (2) the absence of a reliable and clinically feasible method of tracking cognitive recovery in ICU survivors. Our goal is to develop and validate a clinically relevant EEG paradigm that can inform the prognosis of unresponsive, brain-injured patients in the ICU. This protocol describes a study to develop a point-of-care system intended to accurately predict outcomes of unresponsive, brain-injured patients in the ICU. We will recruit 200 continuously-sedated brain-injured patients across five ICUs. Between 24 h and 7 days post-ICU admission, high-density EEG will be recorded from behaviorally unresponsive patients before, during and after a brief cessation of pharmacological sedation. Once patients have reached the waking stage, they will be asked to complete an abridged Cambridge Brain Sciences battery, a web-based series of neurocognitive tests. The test series will be repeated every day during acute admission (ICU, ward), or as often as possible given the constraints of ICU and ward care. Following discharge, patients will continue to complete the same test series on weekly, and then monthly basis, for up to 12 months following injury. Functional outcomes will also be assessed up to 12 months post-injury. We anticipate our findings will lead to an increased ability to identify patients, as soon as possible after their brain injury, who are most likely to survive, and to make accurate predictions about their long-term cognitive and functional outcome. In addition to providing critically needed support for clinical decision-making, this study has the potential to transform our understanding of key functional EEG networks associated with consciousness and cognition.

Higher Fitness Levels Influence Association Between Cognition And Mobility In Older Adults With Hypertension And Dementia Risk

Higher levels of fitness are associated with preserved cognitive function in older adults. Preserved cognition is linked to better mobility and reduced risk of falls. However, it remains to be explored whether cardiovascular fitness (CF) influences the link between cognition and mobility in individuals with cardiovascular disease burden and risk of dementia. PURPOSE: We explored whether CF influences the relationship between cognition and mobility in older adults with hypertension and subjective cognitive decline. These individuals are at higher risk of dementia due to cardiovascular disease burden and early sings of cognitive impairment. METHODS: Older adults (n = 118, age 70.1 (SD = 6.7) years, 62% males) underwent CF assessment (Bruce protocol treadmill stress test) and were grouped based on Bruce protocol stage completion into low (stage 1 [n=31]), average (stage 2 [n=57]), and high (stage ≥3 [n=30]) CF groups. Cognition was measured via the Cambridge Brain Sciences cognitive battery; mobility (usual and dual-task gait [naming animals]) was measured using the GAITRite walkway system. We conduced hierarchical regression models adjusting for sex, age and years of education to determine whether CF modulated association between cognition and mobility. RESULTS: For usual gait, cognition was positively associated with gait velocity in high CF (Change statistics: F(1,25)=14.3, p=.001, R2=.35,), as well as step length in high CF (F(1,25)=10.8, p=.003, R2 =.27) and average CF (F(1,50)=4.4, p=.04, R2 =.08,), and gait variability in average CF (F(1,48)=9.8, p=.003, R2=.17). For dual-task gait, cognition was positively associated with gait velocity in both high CF (F(1,25)=9.15, p=.006, R2=.26) and average CF (F(1,49)=5.8, p=.02, R2 =.10), as well as step length in both high CF group (F(1,25)=7.2, p=.01, R2=.21) and average CF group (F(1,49)=7.2, p=.01, R2 =.13). CONCLUSIONS: Cognition was positively associated with mobility outcomes in individuals with average and high CF, while no associations were seen in those with low CF. These findings suggest that the protective effects of cognition on mobility (e.g., reduced falls risk and prolonged independence) may be hindered by low CF in older adults with hypertension.

Effect of Citicoline on Memory Function in Healthy Order Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract Objectives Subtle deficits in memory in healthy elderly adults are considered to be a normal consequence of aging [i.e., age-associated memory impairment (AAMI)]. The prevalence of cognitive impairment without dementia in the elderly is estimated at 5.4 million, and every year roughly 12% of these individuals go on to develop dementia. Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. Unfortunately, few studies have investigated the effects of citicoline supplementation on memory in healthy elderly adults with memory loss due to aging. Thus, the objective of this study was to investigate the effects of Cognizin®, a citicoline supplement, on memory in healthy elderly populations with AAMI. Methods A total of 100 healthy men and women between 50 to 85 years of age with AAMI participated in this randomized, double-blind, placebo-controlled trial. Subjects were randomized to receive placebo (n = 51) or Cognizin® (n = 49; 500 mg/day) for 12 weeks. Memory functions were assessed at baseline and end of the intervention (12 weeks) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, hematology and clinical chemistry. Results A total of 99 out of 100 subjects completed the study in its entirety. After the 12 week intervention, subjects supplemented with Cognizin® showed significantly greater improvements in episodic memory (assessed by the Paired Associate test) compared to those on placebo. Scores for composite memory, calculated using the scores of four memory tests (Spatial Span, Monkey Ladder, Paired Associate, and Digit Span) also improved to a greater extent following Cognizin® supplementation compared to placebo. There were no adverse events related to a study product and hematology and clinical chemistry were stable throughout the intervention. Conclusions Dietary supplement of Cognizin® for 12 weeks improved overall memory performance, especially episodic memory, in healthy males and females with AAMI. The findings suggest that regular consumption of Cognizin® may be safe and potentially beneficial against memory loss due to aging. Funding Sources Kyowa Hakko Bio Co., Ltd.

Memory Function and Brain Functional Connectivity Adaptations Following Multiple-Modality Exercise and Mind-Motor Training in Older Adults at Risk of Dementia: An Exploratory Sub-Study.

BackgroundMultiple-modality exercise improves brain function. However, whether task-based brain functional connectivity (FC) following exercise suggests adaptations in preferential brain regions is unclear. The objective of this study was to explore memory function and task-related FC changes following multiple-modality exercise and mind–motor training in older adults with subjective cognitive complaints.MethodsWe performed secondary analysis of memory function data in older adults [n = 127, mean age 67.5 (7.3) years, 71% women] randomized to an exercise intervention comprised of 45 min of multiple-modality exercise with additional 15 min of mind-motor training (M4 group, n = 63) or an active control group (M2 group, n = 64). In total, both groups exercised for 60 min/day, 3 days/week, for 24 weeks. We then conducted exploratory analyses of functional magnetic resonance imaging (fMRI) data collected from a sample of participants from the M4 group [n = 9, mean age 67.8 (8.8) years, 8 women] who completed baseline and follow-up task-based fMRI assessment. Four computer-based memory tasks from the Cambridge Brain Sciences cognitive battery (i.e. Monkey Ladder, Spatial Span, Digit Span, Paired Associates) were employed, and participants underwent 5 min of continuous fMRI data collection while completing the tasks. Behavioral data were analyzed using linear mixed models for repeated measures and paired-samples t-test. All fMRI data were analyzed using group-level independent component analysis and dual regression procedures, correcting for voxel-wise comparisons.ResultsOur findings indicated that the M4 group showed greater improvements in the Paired Associates tasks compared to the M2 group at 24 weeks [mean difference: 0.47, 95% confidence interval (CI): 0.08 to 0.86, p = 0.019]. For our fMRI analysis, dual regression revealed significant decrease in FC co-activation in the right precentral/postcentral gyri after the exercise program during the Spatial Span task (corrected p = 0.008), although there was no change in the behavioral task performance. Only trends for changes in FC were found for the other tasks (all corrected p < 0.09). In addition, for the Paired Associates task, there was a trend for increased co-activation in the right temporal lobe (Brodmann Area = 38, corrected p = 0.07), and left middle frontal temporal gyrus (corrected p = 0.06). Post hoc analysis exploring voxel FC within each group spatial map confirmed FC activation trends observed from dual regression.ConclusionOur findings suggest that multiple modality exercise with mind–motor training resulted in greater improvements in memory compared to an active control group. There were divergent FC adaptations including significant decreased co-activation in the precentral/postcentral gyri during the Spatial Span task. Borderline significant changes during the Paired Associates tasks in FC provided insight into the potential of our intervention to promote improvements in visuospatial memory and impart FC adaptations in brain regions relevant to Alzheimer’s disease risk.Clinical Trial RegistrationThe trial was registered in ClinicalTrials.gov in April 2014, Identifier: NCT02136368.

The association between a history of self-reported concussion and response inhibition: a population-based study

ObjectiveWe investigated the long-term cognitive effects of concussion in almost 20,000 members of the general population, using tests that are known to be sensitive to small changes in performance.BackgroundConcussions are the most common type of mild traumatic brain injury, with clinical symptoms such as headaches, dizziness, and nausea, persisting for months post-injury. Despite a growing understanding of the severity and duration of these symptoms, very little is known about the long-term effects of concussion on higher level cognitive functioning and emotional lability.Design/MethodsWe asked 19,261 participants to complete a demographic questionnaire as well as the Cambridge Brain Sciences (CBS) cognitive battery. We divided our sample into two groups: those reporting at least one concussion in their lifetime (post-concussion) and those reporting no concussions in their lifetime (non-concussed). We compared the performance of the two groups on the 12 CBS tasks, as well as on four non-cognitive variables measuring levels of social contact, anxiety, depression, and concentration difficulties.ResultsWe found that post-concussion individuals performed significantly worse on a modified Stroop task that measures aspects of response inhibition, but were no worse on any other cognitive measure, including short-term memory, reasoning, and verbal abilities. Crucially, performance profiles of the post-concussion individuals indicated that they made more errors on trials that involved an incongruent colour/word pair. Beyond measures of cognition, we found that post-concussion participants also reported higher levels of anxiety, depression, and trouble concentrating when compared to the non-concussed group. The number of reported concussions also predicted task scores on this task only.ConclusionsOur results suggest that sustaining a concussion is not associated with long-term global effects on cognition. Those who report at least one concussion appear to have a modest, but statistically significant deficit of response inhibition. This impairment seems to be related to the number of concussions reported.

The effect of transcranial direct current stimulation on the short-term spatial memory in healthy volunteers

Introduction. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation. The application of a weak, subthreshold direct current on the cerebral cortex leads to a change in cortical neuron activity, which continues for a certain amount of time after exposure. The main mechanism of this effect is subthreshold changes in the membrane potential, while the after-effect phenomenon is associated with the influence of tDCS on synaptic plasticity. Study objective. To examine the effect of tDCS of the posterior parietal cortex on certain types of spatial memory with the electrodes positioned P3– P4+ and P3+ P4–. Materials and methods. The study included 18 healthy volunteers (10 men and 8 women) aged 18–23 years. The experiment used stimulation points P3 and P4 according to the 10–20 international electrode positioning system. Stimulation was performed using a direct current of 0.7 mA for 20 min. The study participants underwent three stimulation sessions (P3– P4+, P3+ P4–, P30 P40) in a randomized order with an interval of 3 days between them. After each session, the state of their short-term spatial memory was assessed using the Spatial Memory (categorical spatial memory) and Spatial Span (coordinate spatial memory) tests by Cambridge Brain Sciences, as well as the subjective effect of tDCS. Results. There were no statistically significant differences in the results of neuropsychological tests between ‘active’ stimulation (P3– P4+ and P3+ P4–) and sham stimulation. The lack of effect may be due to the use of insufficient current (0.7 mA) or other factors (duty cycle, electrode location, stimulation time, etc.). No adverse effects of stimulation were reported. Conclusion. tDCS with 0.7 mA current does not affect spatial memory in healthy people when using P3– P4+ and P3+ P4– electrode mountings.