Toward digitally screening and profiling AD: A GAMLSS approach of MemTrax in China.

PURPOSES: To establish a normative range of MemTrax (MTx) metrics in the Chinese population. METHODS: The correct response percentage (MTx-%C) and mean response time (MTx-RT) were obtained and the composite scores (MTx-Cp) calculated. Generalized additive models for location, shape and scale (GAMLSS) were applied to create percentile curves and evaluate goodness of fit, and the speed-accuracy trade-off was investigated. RESULTS: 26,633 subjects, including 13,771 (51.71%) men participated in this study. Age- and education-specific percentiles of the metrics were generated. Q tests and worm plots indicated adequate fit for models of MTx-RT and MTx-Cp. Models of MTx-%C for the low and intermediate education fit acceptably, but not well enough for a high level of education. A significant speed-accuracy trade-off was observed for MTx-%C from 72 to 94. CONCLUSIONS: GAMLSS is a reliable method to generate smoothed age- and education-specific percentile curves of MTx metrics, which may be adopted for mass screening and follow-ups addressing Alzheimer's disease or other cognitive diseases. HIGHLIGHTS: GAMLSS was applied to establish nonlinear percentile curves of cognitive decline. Subjects with a high level of education demonstrate a later onset and slower decline of cognition. Speed-accuracy trade-off effects were observed in a subgroup with moderate accuracy. MemTrax can be used as a mass-screen instrument for active cognition health management advice.

Challenges to be overcome using population-based sampling methods to recruit veterans for a study of post-traumatic stress disorder and traumatic brain injury.

BACKGROUND: Many investigators are interested in recruiting veterans from recent conflicts in Afghanistan and Iraq with Traumatic Brain Injury (TBI) and/or Post Traumatic Stress Disorder (PTSD). Researchers pursuing such studies may experience problems in recruiting sufficient numbers unless effective strategies are used. Currently, there is very little information on recruitment strategies for individuals with TBI and/or PTSD. It is known that groups of patients with medical conditions may be less likely to volunteer for clinical research. This study investigated the feasibility of recruiting veterans returning from recent military conflicts--Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF)--using a population-based sampling method. METHODS: Individuals were sampled from a previous epidemiological study. Three study sites focused on recruiting survey respondents (n = 445) who lived within a 60 mile radius of one of the sites. RESULTS: Overall, the successful recruitment of veterans using a population-based sampling method was dependent on the ability to contact potential participants following mass mailing. Study enrollment of participants with probable TBI and/or PTSD had a recruitment yield (enrolled/total identified) of 5.4%. We were able to contact 146 individuals, representing a contact rate of 33%. Sixty-six of the individuals contacted were screened. The major reasons for not screening included a stated lack of interest in the study (n = 37), a failure to answer screening calls after initial contact (n = 30), and an unwillingness or inability to travel to a study site (n = 10). Based on the phone screening, 36 veterans were eligible for the study. Twenty-four veterans were enrolled, (recruitment yield = 5.4%) and twelve were not enrolled for a variety of reasons. CONCLUSIONS: Our experience with a population-based sampling method for recruitment of recent combat veterans illustrates the challenges encountered, particularly contacting and screening potential participants. The screening and enrollment data will help guide recruitment for future studies using population-based methods.

Episodic memory assessment: effects of sex and age on performance and response time during a continuous recognition task.

Introduction: Continuous recognition tasks (CRTs) assess episodic memory (EM), the central functional disturbance in Alzheimer's disease and several related disorders. The online MemTrax computerized CRT provides a platform for screening and assessment that is engaging and can be repeated frequently. MemTrax presents complex visual stimuli, which require complex involvement of the lateral and medial temporal lobes and can be completed in less than 2 min. Results include number of correct recognitions (HITs), recognition failures (MISSes = 1-HITs), correct rejections (CRs), false alarms (FAs = 1-CRs), total correct (TC = HITs + CRs), and response times (RTs) for each HIT and FA. Prior analyses of MemTrax CRT data show no effects of sex but an effect of age on performance. The number of HITs corresponds to faster RT-HITs more closely than TC, and CRs do not relate to RT-HITs. RT-HITs show a typical skewed distribution, and cumulative RT-HITs fit a negative survival curve (RevEx). Thus, this study aimed to define precisely the effects of sex and age on HITS, CRs, RT-HITs, and the dynamics of RTs in an engaged population. Methods: MemTrax CRT online data on 18,255 individuals was analyzed for sex, age, and distributions of HITs, CRs, MISSes, FAs, TC, and relationships to both RT-HITs and RT-FAs. Results: HITs corresponded more closely to RT-HITs than did TC because CRs did not relate to RT-HITs. RT-FAs had a broader distribution than RT-HITs and were faster than RT-HITs in about half of the sample, slower in the other half. Performance metrics for men and women were the same. HITs declined with age as RT-HITs increased. CRs also decreased with age and RT-FAs increased, but with no correlation. The group over aged 50 years had RT-HITs distributions slower than under 50 years. For both age ranges, the RevEx model explained more than 99% of the variance in RT-HITs. Discussion: The dichotomy of HITs and CRs suggests opposing cognitive strategies: (1) less certainty about recognitions, in association with slower RT-HITs and lower HIT percentages suggests recognition difficulty, leading to more MISSes, and (2) decreased CRs (more FAs) but faster RTs to HITs and FAs, suggesting overly quick decisions leading to errors. MemTrax CRT performance provides an indication of EM (HITs and RT-HITs may relate to function of the temporal lobe), executive function (FAs may relate to function of the frontal lobe), processing speed (RTs), cognitive ability, and age-related changes. This CRT provides potential clinical screening utility for early Alzheimer's disease and other conditions affecting EM, other cognitive functions, and more accurate impairment assessment to track changes over time.

Chinese hospital staff in anxiety and depression: Not only comfort patients but also should be comforted - A nationwide cross-sectional study.

BACKGROUND: Healthcare professionals are in short supply worldwide, especially in China, which can result in increased stress in the work environment and allostatic load for Chinese hospital staff. This study aimed to investigate the prevalence of anxiety and depressive symptoms and their relationship with total stress, allostatic overload, sleep quality, and episodic memory among Chinese hospital staff. METHOD: In this cross-sectional study, self-assessments including Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire-9 (PHQ-9), PsychoSocial Index (PSI), Pittsburgh Sleeping Quality Index (PSQI), and MemTrax test were used to evaluate participants' anxiety symptoms, depressive symptoms, total stress, allostatic load/overload, sleep quality, and episodic memory. RESULTS: A total of 9433 hospital staff from 304 cities participated. Anxiety prevalence was 21.0 % (95 % confidential interval (CI) 20.2 %, 21.8 %), while the prevalence of depressive symptoms was at 21.4 % (95 % CI 20.5 %, 22.2 %). 79.8 % (95 % CI 79.0 %, 80.6 %) of the hospital staff had allostatic overload. Poor sleep quality affected 50.4 % of participants, and 32.1 % experienced poor episodic memory. LIMITATIONS: This study utilized a convenience sampling approach, relying on an online survey as its data collection method. CONCLUSIONS: Hospital staff in China are facing a stressful environment with a high prevalence of anxiety and depressive symptoms, significant allostatic overload, poor sleep quality, and compromised episodic memory. It is imperative that local management and community structures enhance their support and care for these essential workers, enabling them to manage and withstand the stresses of their professional roles effectively.

Posttraumatic Stress Disorder-Associated Cognitive Deficits on the Repeatable Battery for the Assessment of Neuropsychological Status in a Veteran Population.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a frequent problem of veterans receiving care and is often associated with cognitive deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well-validated cognitive screening measure often used in the US Department of Veterans Affairs (VA), particularly in neurorehabilitation settings. However, the influence of PTSD on RBANS performance is unclear, particularly within a heterogeneous VA outpatient population in which PTSD and traumatic brain injury (TBI) may not be the primary focus of care. METHODS: Participants included 153 veterans with complex deployment-related health problems, including a diagnosis of PTSD (n = 98) and a history of TBI (n = 92). All veterans completed a targeted cognitive battery that included the Wechsler Test of Adult Reading, the Wechsler Adults Intelligence Scale, measure assessing processing speed, attention, and cognitive flexibility, and RBANS. RESULTS: A diagnosis of PTSD was associated with worse performance on the Story Recall subtest of the RBANS, but not on any other cognitive measures. A diagnosis of mild TBI, or co-occurring PTSD and TBI did not predict cognitive performance on any measures. CONCLUSIONS: The RBANS best captured cognitive deficits associated with PTSD compared with a history of mild TBI or co-occurring mild TBI and PTSD. These findings may provide insight into the interpretation and attribution of cognitive deficits in the veteran population.

Treatment of Alzheimer's Disease: Trazodone, Sleep, Serotonin, Norepinephrine, and Future Directions.

In this issue, an article by La et al. provides evidence that trazodone delayed cognitive decline in 25 participants with Alzheimer's disease (AD), mild cognitive impairment, or normal cognition. For participants considered to have AD pathology, trazodone non-users declined at a rate 2.4 times greater than those taking trazodone for sleep over a 4-year period. In the analysis of sleep complaints, the relationship between trazodone, a widely used medication for sleep problems in the elderly, and cognition was associated with subjective improvement of sleep disruption. Due to the design of the study, it was not possible to prove that the benefit of slowing cognitive decline was due specifically to the improvement in sleep. However, trazodone uniquely improves the deeper phases of slow-wave sleep. Other sedative medications are generally associated with worse cognitive function over time, and they do not improve sleep characteristics as does trazodone. Trazodone has a variety of effects on several monoaminergic mechanisms: a potent serotonin 5-HT2A and α1-adrenergic receptor antagonist, a weak serotonin reuptake inhibitor, and a weak antihistamine or histamine H1 receptor inverse agonist. Because of the potential importance of this finding, further discussion is provided on the roles that trazodone may play in the modulation of monoamines, cognition, and the development of AD. If trazodone really does provide such a dramatic slowing in the development of dementia associated with AD, a great deal more research on trazodone is needed, including environmental and behavioral factors related to improvement of sleep, energy management, and neuroplasticity.

Findings from the National Memory Screening Day program.

OBJECTIVES: To report experience with a large, nation-wide public memory screening program. DESIGN: Descriptive study of community-dwelling elderly adults. SETTING: Local community sites (48 sites agreed to provide data) throughout the United States participating in National Memory Screening Day in November 2010. PARTICIPANTS: Of 4,369 reported participants, 3,064 had complete data records and are included in this report. MEASUREMENTS: Participants completed a questionnaire that included basic demographic information and a question about subjective memory concerns. Each site selected one of seven validated cognitive screening tests: Mini-Cog, General Practitioner assessment of Cognition, Memory Impairment Screen, Kokmen Short Test of Mental Status, Mini-Mental State Examination, Montreal Cognitive Assessment, Saint Louis University Mental Status Examination. RESULTS: Overall, 11.7% failed one of the seven screening tests. As expected, failure rates were higher in older and less-educated participants (P's < .05). Subjective memory concerns were associated with a 40% greater failure rate for persons of similar age and education but no memory concerns (odds ratio = 1.4, 95% confidence interval = 1.07-1.78), although only 11.9% of those who reported memory concerns (75% of all participants) had detectible memory problems. CONCLUSION: Screening for cognitive impairment in community settings yielded results consistent with expected effects of age and education. The event attracted a large proportion of individuals with memory concerns; 88.1% were told that they did not have memory problems detectible with the tests used. Further studies are needed to assess how participants respond to and use screening information, whether this information ultimately influences decision-making or outcomes, and whether memory screening programs outside healthcare settings have public health value.

Ethics review as a catalyst for progress.

There are several points where ethical decision-making has become paralyzed and inefficient as the field of Alzheimer's disease study has advanced. The focus of this review is to highlight these points and several lines of research that can inform ethical decision-making. The goal is to identify barriers and to move toward solutions. Examples of other fields of study that can be particularly useful for innovative ways to study effective ethical decision-making include implementation science and neuroscience of decision-making, as well as therapeutic investigations of other domains such as the human biology and psychology.