Cognitive Outcome Measures Research Articles

Transcranial magnetic stimulation and transcranial direct current stimulation: treatments for cognitive and neuropsychiatric symptoms in the neurodegenerative dementias?

IntroductionTwo methods of non-invasive brain stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have demonstrable positive effects on cognition and can ameliorate neuropsychiatric symptoms such as depression. Less is known about the efficacy of these approaches in common neurodegenerative diseases. In this review, we evaluate the effects of TMS and tDCS upon cognitive and neuropsychiatric symptoms in the major dementias, including Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), and frontotemporal dementia (FTD), as well as the potential pre-dementia states of Mild Cognitive Impairment (MCI) and Parkinson’s disease (PD).MethodsPubMed (until 7 February 2014) and PsycINFO (from 1967 to January Week 3 2014) databases were searched in a semi-systematic manner in order to identify relevant treatment studies. A total of 762 studies were identified and 32 studies (18 in the dementias and 14 in PD populations) were included.ResultsNo studies were identified in patients with PDD, FTD or VaD. Of the dementias, 13 studies were conducted in patients with AD, one in DLB, and four in MCI. A total of 16 of the 18 studies showed improvements in at least one cognitive or neuropsychiatric outcome measure. Cognitive or neuropsychiatric improvements were observed in 12 of the 14 studies conducted in patients with PD.ConclusionsBoth TMS and tDCS may have potential as interventions for the treatment of symptoms associated with dementia and PD. These results are promising; however, available data were limited, particularly within VaD, PDD and FTD, and major challenges exist in order to maximise the efficacy and clinical utility of both techniques. In particular, stimulation parameters vary considerably between studies and are likely to subsequently impact upon treatment efficacy.

Assessing cognition and function in Alzheimer's disease clinical trials: Do we have the right tools?

Several lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging—Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre-symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28–29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD.

A cognitive-balance control training paradigm using wii fit to reduce fall risk in chronic stroke survivors.

The impaired ability to maintain balance while performing higher-level cognitive tasks (cognitive-motor interference) significantly predisposes stroke survivors to risk of falls. We investigated adherence and intervention-related effects of gaming to improve balance control and decrease cognitive-motor interference in stroke survivors. Community-dwelling individuals with hemiparetic stroke (N = 8) received balance control training using Wii Fit in conjunction with cognitive training for approximately 110 min/d for 5 consecutive days. Changes in balance and cognitive performance were evaluated by the limits of stability test performed under single-task (ST) and dual-task (DT) conditions. The outcome measures from the limits of stability test included reaction time and movement velocity of the center of pressure. The cognitive performance was quantified by the number of errors. The DT cost was computed for the balance and cognitive outcome measures using [(ST - DT)/ST × 100]. Adherence was assessed by change on the Intrinsic Motivation Inventory scores postintervention. No commercial party having a direct financial interest in the research findings reported here has conferred orwill confer. Posttraining, reaction time cost in the forward direction improved from 31 ± 8.02 to ±8.7 ± 6.6. Similarly, movement velocity cost improved from 33.7 ± 12.3 to 11 ± 1. Cognitive cost also decreased from 47.9 ± 13.9 to 20 ± 18.8. There were similar improvements in the backward direction for all the outcome measures. Scores on the Intrinsic Motivation Inventory improved from 16.6 ± 1.3 to 23.5 ± 1.5. The results demonstrate good adherence and evidence of clinical value of this high-intensity, short-duration protocol for reducing cognitive-motor interference and improving balance control in stroke survivors. Future studies should examine the dose-response effects and long-term changes of such DT training paradigm applied to improve fall efficacy.Video Abstract available. See Video (Supplemental Digital Content 1, http://links.lww.com/JNPT/A80) for more insights from the authors.

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Examining the association between late-life depressive symptoms, cognitive function, and brain volumes in the context of cognitive reserve.

The present study aimed to investigate whether cognitive reserve moderated the association between depressive symptoms and cognition, as well as brain volumes in a sample of older adults. Non-demented participants (n = 3484) were selected from the Washington Heights/Hamilton Heights Inwood Columbia Aging Project (Northern Manhattan). A subsample of these participants without dementia (n = 703), who had brain imaging data, was also selected for a separate analysis. Depressive symptomatology was assessed with the 10-item Center for Epidemiologic Studies Depression Scale. Reading level and years of education were used as measures of cognitive reserve. Four distinct cognitive composite scores were calculated: executive function, memory, visual-spatial, and language. Multiple regression analysis revealed interaction effects between both measures of cognitive reserve and depressive symptoms on all the cognitive outcome measures except for visual-spatial ability. Those with greater reserve showed greater cognitive decrements than those with lower levels of reserve as depressive symptoms increased. A borderline interaction effect was revealed between reading level and depressive symptoms on total brain volumes. Those with lower reading scores showed greater volume loss as depressive symptoms increased than those with higher reading scores. Our findings indicate that the association between late-life depressive symptoms and core aspects of cognition varies depending on one's level of cognitive reserve. Those that had greater levels of education and/or reading ability showed a greater decrease in memory, executive, and language performances as depressive symptoms increased than those with lower years of education and reading ability.

Augmenting one-session treatment of children's specific phobias with attention training to positive stimuli

This study examined the efficacy of combining two promising approaches to treating children's specific phobias, namely attention training and one 3-h session of exposure therapy (‘one-session treatment’, OST). Attention training towards positive stimuli (ATP) and OST (ATP+OST) was expected to have more positive effects on implicit and explicit cognitive mechanisms and clinical outcome measures than an attention training control (ATC) condition plus OST (ATC+OST). Thirty-seven children (6–17 years) with a specific phobia were randomly assigned to ATP+OST or ATC+OST. In ATP+OST, children completed 160 trials of attention training responding to a probe that always followed the happy face in happy-angry face pairs. In ATC+OST, the probe appeared equally often after angry and happy faces. In the same session, children completed OST targeting their phobic situation/object. Clinical outcomes included clinician, parent and child report measures. Cognitive outcomes were assessed in terms of change in attention bias to happy and angry faces and in danger and coping expectancies. Assessments were completed before and after treatment and three-months later. Compared to ATC+OST, the ATP+OST condition produced (a) significantly greater reductions in children's danger expectancies about their feared situations/object during the OST and at three-month follow-up, and (b) significantly improved attention bias towards positive stimuli at post-treatment, which in turn, predicted a lower level of clinician-rated phobia diagnostic severity three-months after treatment. There were no significant differences between ATP+OST and ATC+OST conditions in clinician, parent, or child-rated clinical outcomes. Training children with phobias to focus on positive stimuli is effective in increasing attention towards positive stimuli and reducing danger expectancy biases. Studies with larger sample sizes and a stronger ‘dose’ of ATP prior to the OST may reveal promising outcomes on clinical measures for training attention towards positive stimuli.

Serum cholesterol and cognitive functions: the Lothian Birth Cohort 1936.

We examined the associations between serum cholesterol measures, statin use, and cognitive function measured in childhood and in old age. The possibility that lifelong (trait) cognitive ability accounts for any cross-sectional associations between cholesterol and cognitive performance in older age, seen in observational studies, has not been tested to date. Participants were 1,043 men and women from the Lothian Birth Cohort 1936 Study, most of whom had participated in a nationwide IQ-type test in childhood (Scottish Mental Survey of 1947), and were followed up at about age 70 years. Serum cholesterol measures included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and cholesterol:HDL cholesterol ratio. Cognitive outcome measures were age 70 IQ (using the same test as at age 11 years), general cognitive ability (g), processing speed, memory, and verbal ability. Higher TC, higher HDL-C, and lower triglycerides were associated with higher age 70 cognitive scores in most cognitive domains. These relationships were no longer significant after covarying for childhood IQ, with the exception a markedly attenuated association between TC and processing speed, and triglycerides and age 70 IQ. In the fully adjusted model, all conventionally significant (p < 0.05) effects were removed. Childhood IQ predicted statin use in old age. Statin users had lower g, processing speed, and verbal ability scores at age 70 years after covarying for childhood IQ, but significance was lost after adjusting for TC levels. These results suggest that serum cholesterol and cognitive function are associated in older age via the lifelong stable trait of intelligence. Potential mechanisms, including lifestyle factors, are discussed.

Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data.

Vortioxetine, a novel antidepressant for the treatment of major depressive disorder (MDD), is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and serotonin (5-HT) transporter (SERT) inhibitor. Here we review its preclinical and clinical properties and discuss translational aspects. Vortioxetine increases serotonergic, noradrenergic, dopaminergic, cholinergic, histaminergic and glutamatergic neurotransmission in brain structures associated with MDD. These multiple effects likely derive from its interaction with 5-HT-receptor-mediated negative feedback mechanisms controlling neuronal activity. In particular, 5-HT3 receptors may play a prominent role, since their blockade i) increases pyramidal neuron activity by removing 5-HT3 receptor-mediated excitation of GABA interneurons, and ii) augments SSRI effects on extracellular 5-HT. However, modulation of the other 5-HT receptor subtypes also likely contributes to vortioxetine's pharmacological effects. Preclinical animal models reveal differences from SSRIs and SNRIs, including antidepressant-like activity, increased synaptic plasticity and improved cognitive function. Vortioxetine had clinical efficacy in patients with MDD: 11 placebo-controlled studies (including one in elderly) with efficacy in 8 (7 positive, 1 supportive), 1 positive active comparator study plus a positive relapse prevention study. In two positive studies, vortioxetine was superior to placebo in pre-defined cognitive outcome measures. The clinically effective dose range (5-20mg/day) spans ~50 to >80% SERT occupancy. SERT and 5-HT3 receptors are primarily occupied at 5mg, while at 20mg, all targets are likely occupied at functionally relevant levels. The side-effect profile is similar to that of SSRIs, with gastrointestinal symptoms being most common, and a low incidence of sexual dysfunction and sleep disruption possibly ascribed to vortioxetine's receptor modulation.

Effects of Repeated Anodal tDCS Coupled With Cognitive Training for Patients With Severe Traumatic Brain Injury

To determine whether cumulative anodal transcranial direct current stimulation (A-tDCS) of the left dorsolateral prefrontal cortex (DLPFC) could enhance rehabilitation of memory and attention in patients with traumatic brain injury (TBI). Inpatient and outpatient neurorehabilitation unit. Twenty-three adult patients, 4- to 92- months post severe TBI. Participants were randomly allocated to 2 groups. The experimental group received A-tDCS (10 minutes; 1 mA; in the DLPFC), followed by rehabilitative cognitive training, daily for 15 days. Controls received A-tDCS for 25 seconds (sham condition) with the same rehabilitation. Battery of memory and attention tests, which included visual and auditory modalities. Participants were tested twice before beginning rehabilitation (to control for spontaneous recovery), after rehabilitation completion, and 4 months later. Tests scores in both groups were similar at 3 weeks before and immediately before treatment. After treatment, the experimental group exhibited larger effect sizes in 6 of 8 cognitive outcome measures, but they were not significantly different from controls. At follow-up, differences remained insignificant. In contrast to previous studies, our study did not provide sufficient evidence to support the efficacy of repeated A-tDCS for enhancing rehabilitation of memory and attention in patients after severe TBI.

Effects of correcting for prematurity on cognitive test scores in childhood

The American Academy of Pediatrics recommends that test scores should be corrected for prematurity up to 3 years of age, but this practice varies greatly in both clinical and research settings. The aim of this study was to contrast the effects of using chronological age and those of using corrected age on measures of cognitive outcome across childhood. A theoretical model was constructed using norms from the Bayley Scales of Infant and Toddler Development, Third Edition; the Wechsler Preschool and Primary Scale of Intelligence, Third Edition Australian; and the Wechsler Intelligence Scales for Children, Fourth Edition Australian. Baseline scores representing different levels of functioning (70, below average; 85, borderline; and 100, average) were recalculated using the normative data for ages 6 months to 16 years to account for 1, 2, 3 and 4 months of prematurity. The model created depicted the difference in standardised scores between chronological and corrected age. Compared with scores corrected for prematurity, the absolute reduction in scores using chronological age was greater for increasing degree of prematurity, younger ages at assessment and higher baseline scores and was substantial even beyond 3 years of age. However, the pattern was erratic, with considerable fluctuation evident across different ages and baseline scores. Chronological age results in a lowering of scores at all ages for preterm-born subjects that is greater in the first few years and in those born at earlier gestational ages. Whether or not to correct for prematurity depends upon the context of the assessment.

Birth weight and cognitive function in early adulthood: the Australian Aboriginal birth cohort study.

It has been suggested that in addition to genetic factors, fetal and post-natal growth influence cognition in early adulthood. However, most studies have been in developed populations, so it is unclear if the same findings would be seen in other, less developed, settings, and have used testing tools not applicable to an Australia Aboriginal population. This study investigated the relationships between cognitive function in early adulthood and birth weight and contemporary height. Simple reaction time (SRT), choice reaction time (CRT) and working memory (WM) were assessed using the CogState battery. A significant association was seen between birth weight and SRT in early adulthood, but not with the other two cognitive measures. Urban dwellers had significantly shorter SRT and CRT than their remote counterparts. Contemporary body mass index and maternal age were associated with CRT. Only fetal growth restriction was associated with WM, with greater WM in those with restricted growth. No associations were seen with contemporary height. These results suggest that fetal growth may be more important than the factors influencing post-natal growth in terms of cognition in early adulthood in this population, but that the associations may be inconsistent between cognitive outcomes. Further research is required to identify whether similar associations are seen in other, similar, populations and to assess why differences in cognitive outcome measures are seen.

Hyperbaric oxygen for blast‐related postconcussion syndrome: Three‐month outcomes

Mild traumatic brain injury (mTBI) and postconcussion syndrome (PCS) are common among military combatants. Hyperbaric oxygen (HBO2 ) is a proposed treatment for these conditions, but it has not been rigorously studied. The objective of this study was to determine the effects of HBO2 by 3 months post compression at 2 commonly employed dosing levels to treat PCS; whether specific subgroups may have benefited; and if no overall effect was found, whether benefit is masked by other conditions. This randomized, double-blind, sham-controlled study was conducted at the Naval Air Station in Pensacola, Florida on 61 male Marines with a history of mTBI and PCS. Intervention consisted of 40 once daily 60-minute hyperbaric chamber compressions at 2.0 atmospheres absolute (ATA) at 1 of 3 randomly preassigned oxygen fractions, resulting in respective blinded groups with an oxygen-breathing exposure equivalent to (1) surface air (sham), (2) 100% oxygen at 1.5ATA, or (3) 100% oxygen at 2.0ATA. The main outcome measure was the Rivermead Post-Concussion Questionnaire-16 (RPQ-16) collected before compressions and at 2 later points. The interaction of time by intervention group was not significant for improvement on the RPQ-16. Nor was there evidence of efficacy on the RPQ-16 for any subgroup. No significant time by intervention interaction was found for any functional, cognitive, or psychomotor secondary outcome measure at an unadjusted 0.05 significance level. Using a randomized control trial design and analysis including a sham, results showed no evidence of efficacy by 3 months post-compression to treat the symptomatic, cognitive, or behavioral sequelae of PCS after combat-related mTBI.

Treatment effects in multiple cognitive domains in Alzheimer's disease: a two-year cohort study.

IntroductionDespite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer’s disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort.MethodsA cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE).ResultsAt one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function.ConclusionsThe present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system.

A Randomised Placebo-Controlled Trial to Differentiate the Acute Cognitive and Mood Effects of Chlorogenic Acid from Decaffeinated Coffee

In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB) or 540mg pure chlorogenic acids (CGA) or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP). Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT), Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS). No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05), as well as decision time on a 2-choice reaction time task (Jensen box) in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05). Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02) and the caffeine Research VAS relative to CGA (t=3.09, p=0.009) and placebo (t=2.75,p=0.02) at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively), whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively). These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be attributable to CGAs.Trial Registration: Australia New Zealand Clinical Trials Registry ACTRN12611000067976 www.anzctr.org.au

Puzzling With Online Games (BAM-COG): Reliability, Validity, and Feasibility of an Online Self-Monitor for Cognitive Performance in Aging Adults

BackgroundOnline interventions are aiming increasingly at cognitive outcome measures but so far no easy and fast self-monitors for cognition have been validated or proven reliable and feasible.ObjectiveThis study examines a new instrument called the Brain Aging Monitor–Cognitive Assessment Battery (BAM-COG) for its alternate forms reliability, face and content validity, and convergent and divergent validity. Also, reference values are provided.MethodsThe BAM-COG consists of four easily accessible, short, yet challenging puzzle games that have been developed to measure working memory (“Conveyer Belt”), visuospatial short-term memory (“Sunshine”), episodic recognition memory (“Viewpoint”), and planning (“Papyrinth”). A total of 641 participants were recruited for this study. Of these, 397 adults, 40 years and older (mean 54.9, SD 9.6), were eligible for analysis. Study participants played all games three times with 14 days in between sets. Face and content validity were based on expert opinion. Alternate forms reliability (AFR) was measured by comparing scores on different versions of the BAM-COG and expressed with an intraclass correlation (ICC: two-way mixed; consistency at 95%). Convergent validity (CV) was provided by comparing BAM-COG scores to gold-standard paper-and-pencil and computer-assisted cognitive assessment. Divergent validity (DV) was measured by comparing BAM-COG scores to the National Adult Reading Test IQ (NART-IQ) estimate. Both CV and DV are expressed as Spearman rho correlation coefficients.ResultsThree out of four games showed adequate results on AFR, CV, and DV measures. The games Conveyer Belt, Sunshine, and Papyrinth have AFR ICCs of .420, .426, and .645 respectively. Also, these games had good to very good CV correlations: rho=.577 (P=.001), rho=.669 (P<.001), and rho=.400 (P=.04), respectively. Last, as expected, DV correlations were low: rho=−.029 (P=.44), rho=−.029 (P=.45), and rho=−.134 (P=.28) respectively. The game Viewpoint provided less desirable results with an AFR ICC of .167, CV rho=.202 (P=.15), and DV rho=−.162 (P=.21).ConclusionsThis study provides evidence for the use of the BAM-COG test battery as a feasible, reliable, and valid tool to monitor cognitive performance in healthy adults in an online setting. Three out of four games have good psychometric characteristics to measure working memory, visuospatial short-term memory, and planning capacity.

Neuroanatomical correlates of cognitive functioning in prodromal Huntington disease

IntroductionThe brain mechanisms of cognitive impairment in prodromal Huntington disease (prHD) are not well understood. Although striatal atrophy correlates with some cognitive abilities, few studies of prHD have investigated whether cortical gray matter morphometry correlates in a regionally specific manner with functioning in different cognitive domains. This knowledge would inform the selection of cognitive measures for clinical trials that would be most sensitive to the target of a treatment intervention.MethodIn this study, random forest analysis was used to identify neuroanatomical correlates of functioning in five cognitive domains including attention and information processing speed, working memory, verbal learning and memory, negative emotion recognition, and temporal processing. Participants included 325 prHD individuals with varying levels of disease progression and 119 gene-negative controls with a family history of HD. In intermediate analyses, we identified brain regions that showed significant differences between the prHD and the control groups in cortical thickness and striatal volume. Brain morphometry in these regions was then correlated with cognitive functioning in each of the domains in the prHD group using random forest methods. We hypothesized that different regional patterns of brain morphometry would be associated with performances in distinct cognitive domains.ResultsThe results showed that performances in different cognitive domains that are vulnerable to decline in prHD were correlated with regionally specific patterns of cortical and striatal morphometry. Putamen and/or caudate volumes were top-ranked correlates of performance across all cognitive domains, as was cortical thickness in regions related to the processing demands of each domain.ConclusionsThe results underscore the importance of identifying structural magnetic resonance imaging (sMRI) markers of functioning in different cognitive domains, as their relative sensitivity depends on the extent to which processing is called upon by different brain networks. The findings have implications for identifying neuroimaging and cognitive outcome measures for use in clinical trials.

Effects of interactive metronome therapy on cognitive functioning after blast-related brain injury: A randomized controlled pilot trial.

We report preliminary findings on the efficacy of interactive metronome (IM) therapy for the remediation of cognitive difficulties in soldiers with persisting cognitive complaints following blast-related mild-to-moderate traumatic brain injury (TBI). Forty-six of a planned sample of 50 active duty soldiers with persistent cognitive complaints following a documented history of blast-related TBI of mild-to-moderate severity were randomly assigned to receive either standard rehabilitation care (SRC) or SRC plus a 15-session standardized course of IM therapy. Primary outcome measures were Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Index Scores. Secondary outcome measures included selected subtests from the Delis-Kaplan Executive Functioning System (Trail Making Test and Color-Word Interference) and the Wechsler Adult Intelligence Scale-Fourth Edition (Symbol Search, Digit-Symbol Coding, Digit Span, and Letter-Number Sequencing) as well as the Integrated Visual and Auditory Continuous Performance Test. Significant group differences (SRC vs. IM) were observed for RBANS Attention (p = .044), Immediate Memory (p = .019), and Delayed Memory (p = .031) indices in unadjusted analyses, with the IM group showing significantly greater improvement at Time 2 than the SRC group, with effect sizes in the medium-to-large range in the adjusted analyses for each outcome (Cohen's d = 0.511, 0.768, and 0.527, respectively). Though not all were statistically significant, effects in 21 of 26 cognitive outcome measures were consistently in favor of the IM treatment group (binomial probability = .00098). The addition of IM therapy to SRC appears to have a positive effect on neuropsychological outcomes for soldiers who have sustained mild-to-moderate TBI and have persistent cognitive complaints after the period for expected recovery has passed.

Effect of Donepezil in Alzheimer Disease Can Be Measured by a Computerized Human Analog of the Morris Water Maze

Background: Drug development for Alzheimer disease (AD) is challenged by the success in animal models tested in the Morris water maze (MWM) and the subsequent failures to meet primary outcome measures in phase II or III clinical trials in patients. The human variant of MWM (hMWM) enables us to examine allocentric and egocentric navigation as in the MWM. Objective: It was the aim of this study to examine the utility of a computerized hMWM to assess the effects of donepezil in mild AD. Methods: Donepezil 5 mg/day was started after initial hMWM testing in the treated group (n = 12), and after 28 days, the dose was increased to 10 mg/day. The performance after 3 months was compared to that of a non-treated group (n = 12). Results: Donepezil stabilized or improved the spatial navigation performance after 3 months, especially in the allocentric delayed recall subtask (p = 0.014). Conclusions: The computerized hMWM has the potential to measure the effects of donepezil in mild AD. It is a sensitive cognitive outcome measure in AD clinical trials.

Development of a short form of Stroke-Specific Quality of Life Scale for patients after aneurysmal subarachnoid hemorrhage

BackgroundThe identification of aneurysmal subarachnoid hemorrhage (aSAH) patients with a decrease in health-related quality of life (HRQOL) is challenging. Stroke-Specific Quality of Life (SS-QOL) Scale is one of the commonest disease-specific quality of life measures initially developed and validated for ischemic stroke patients. A disadvantage is subject burden and a short form is more practical to use in clinical and research setting. AimThis study aimed to develop a short form (12-item) of a Chinese version of Stroke-Specific Quality of Life Scale for aSAH (SSQOL-a) for clinical and research applications. MethodsWe carried out a prospective observational assessor-blinded multi-center study in Hong Kong. The study was registered at ClinicalTrials.gov of the U.S. National Institutes of Health (NCT01038193), and was approved by hospital ethics committees. ResultsOne hundred and eighty-six aSAH patients were recruited over a 30month period during admission. One hundred (54%) aSAH patients completed the 12-month assessment battery and were included into the current study. The total score, physical component score, and psychosocial score of the 12-item Chinese version showed satisfactory internal consistency and explained high percentages of variance of the full Chinese version (92% to 96%). The 12-item Chinese version showed significant correlations with neurological, functional, generic quality of life, psychiatric, and cognitive outcome measures at 12months. Chinese version calculated physical subscore had better discrimination in detecting complete recovery than the Dutch version calculated physical subscore in our Chinese population. ConclusionsThe 12-item Chinese version of SSQOL-a has a satisfactory internal consistency and criterion validity for SAH patients at 12month assessments.

P 237. Repeated anodal tDCS coupled with cognitive training for patients with severe traumatic brain injury-a pilot RCT

Does repeated anodal transcranial direct current stimulation (A-tDCS) of the left dorso-lateral prefrontal cortex (DLPFC) enhance cognitive rehabilitation effects on memory and attention in patients with traumatic brain injury (TBI). Twenty-three adult patients, 4–92 months post severe TBI, were randomly allocated to two groups. The experimental group received A-tDCS (10 min; 1 mA; in the DLPFC), followed by 1-h cognitive training, daily for 15 days. Controls received A-tDCS for 25 s (sham condition) with the same rehabilitation programme. Effects of the treatment were assessed using a battery of memory and attention tests (Rey’s Auditory Verbal Learning Test, Paced Auditory Serial Addition Test, Cambridge Neuropsychological Test Automated Battery), which included visual and auditory modalities. Additionally, European Brain Injury Questionaire was used to assess functional gains in daily activities. Participants were tested twice before beginning rehabilitation (to control for spontaneous recovery), after rehabilitation completion, and four months later. Tests scores in both groups were similar at three weeks before and immediately before treatment. After treatment, the experimental group exhibited larger effect sizes in six out of eight cognitive outcome measures, but they were not significantly different from controls. At follow-up, experimental group’s effect sizes were higher in five outcome measures. However, differences remained insignificant. No serious adverse effects were observed during the programme. In contrast to previous studies, our study did not provide sufficiently strong evidence to support the efficacy of repeated A-tDCS over the left DLPFC for enhancing rehabilitation of memory and attention in patients after severe TBI. However, effect sizes suggested a positive response to stimulation.