Conduct secondary analyses on longitudinal data to determine if caregiver-reported sleep quantity and sleep problems across early childhood (ages 2 - 5 years) predict their child’s attention and executive functioning at age 8 years.

This study utilized data from the Health Outcomes and Measures of the Environment (HOME) Study. The HOME Study recruited pregnant women from 20032006 within a nine-county area surrounding Cincinnati, OH. Caregivers reported on their child’s sleep patterns when children were roughly 2, 2.5, 3, 4, and 5 years of age. Our analysis included 410 participants from the HOME Study where caregivers reported sleep measures on at least 1 occasion or their child completed an assessment of attention and executive functioning at age 8. At each time point, caregiver report on an adapted version of the Child Sleep Habits Questionnaire (CSHQ) was used to determine: (1) total sleep time (TST; “your child’s usual amount of sleep each day, combining nighttime sleep and naps”) and (2) overall sleep problems (23 items related to difficulties with sleep onset, sleep maintenance, and nocturnal events). Our outcome variables, collected at age 8, included caregiver-report forms and measures of attention and executive functioning. Caregiver report measures included normed scores on the Behavior Rating Inventory of Executive Function, from which we focused on the Behavior Regulation Index (BRIEF BRI) and Metacognition Index (BRIEF MI). Performance based measures included T-scores for Omission and Commission errors on the Conner’s Continuous Performance Test, Second Edition (CPT-2) and Standard Scores on the WISC-IV; Working Memory Index (WMI). We used longitudinal growth curve models of early childhood sleep patterns to predict attention and executive functioning at age 8. Predictive analyses were run with and without key covariates: annual household income, child sex and race. To account for general intellectual functioning, we also included covariates children’s WISC-IV Verbal Comprehension and Perceptual Reasoning Indexes.

Children in our sample were evenly divided by sex; 60% were White. Sleep problems did not show linear or quadratic change over time, so an intercept-only model was used. Sleep problems did not predict any of our outcome measures at age 8 in unadjusted or covariate-adjusted models. As expected, sleep duration was shorter as children matured, so predictive models examined both intercept and slope. Slope was negatively associated with CPT-2 Commissions (unadjusted p=.047; adjusted p=.013); children who showed the least decline in sleep over time had fewer impulsive errors at age 8. The sleep duration intercept was negatively associated with BRIEF BRI (unadjusted p=.002; adjusted p=.043); children who slept less across early childhood had worse parent-reported behavioral regulation at age 8. Neither sleep duration slope nor intercept significantly predicted any other outcomes at age 8 in unadjusted or covariate-adjusted analyses.

Total sleep time across early childhood predicts behavior regulation difficulties in later childhood. Inadequate sleep during early childhood may be a marker for or contribute to poor development of a child’s self-regulatory skills.

Previous research indicates that women tend to struggle with insomnia at higher rates both prior to and during the global COVID-19 pandemic; however, not much research has investigated the extent to which insomnia correlates with comorbid problems, including aggression, depression, anxiety, PTSD severity, and alcohol use between the sexes. On a neurobiological level, insomnia could be associated with those mood disorders due to the effects of sleep disturbance on serotonergic and GABA neurotransmission, and males might experience such associations at a lower frequency due to their increased rates of serotonin synthesis. Consequently, we hypothesized that women would demonstrate higher prevalence of the aforementioned comorbidities during COVID than males due to higher rates of insomnia reported in women during COVID.

We surveyed a total of 13,313 adults, with 5,598 females (Mage=36.4, SD=11.9) and 7,654 males (Mage=37.81, SD=12.7) using Amazon Mechanical Turk between April 2020 and April 2021. Insomnia was measured using the Insomnia Severity Index (ISI), while levels of depression, anxiety, PTSD severity, and alcohol use, and aggression were assessed through Patient Stress Questionnaires (PSQs) and the Buss Perry Aggression Questionnaire (BPAQ).

As expected, there were significant positive correlations between ISI and BPAQ (r(13306)=0.364, p<0.0001), PSQ Depression (r(13300)=0.694, p<0.0001), PSQ Anxiety (r(13211)=0.627, p<0.0001), PSQ PTSD (r(13305)=0.444, p<0.0001), and PSQ Alcohol (r(12915)=0.218, p<0.001). The strength of these associations was significantly higher in males than females in almost all categories: aggression (z=4.27, p<0.0001), depression (z=2.41, p=0.016), anxiety (z=3.16, p=0.0016), and alcohol use (z=5.89, p<0.0001) - not significant for PTSD severity (z=1.48, p=0.14).

We found that insomnia was more strongly correlated with comorbid emotional and behavioral problems among males than females. This stands in contrast to our initial hypothesis, as the findings suggest that men who suffer from greater insomnia are more likely to experience those four comorbidities than females. This suggests that sex may play a role in the association between sleep disturbances and other clinical presentations relevant to neuropsychology. Further work will be necessary to identify the neurobiological mechanisms that drive the sex differences in these associations. While the present findings cannot determine the causal direction of the association, it will be crucial to determine the directionality of these associations and the mechanisms that lead to differences in expression between the sexes.

REM sleep behavior disorder (RBD) is a parasomnia characterized by vivid dreams and motor behavior such that people appear to “act out their dreams.” These are sudden and often violent bodily movements such as punching or kicking, or vocalizations such as laughing or shouting. RBD is mostly associated with the older adult male population. However, recent studies show that RBD and REM sleep without atonia (RSWA) also occur in other populations, including women, children, and adolescents. Given the prodromal period before an individual can develop the classic symptoms of RBD and that RBD is not just limited to older adult males, it is important to study subclinical features of RBD. RBD is a parasomnia and poor sleep is well known to affect cognitive domains. Additionally, RBD is separately shown to negatively affect cognition in older adults. Given these connections, the association between RBD symptoms and cognition among young adults warrants further study. The purpose of this study was to evaluate the association between RBD symptoms and cognitive domains, specifically attention, processing speed, executive function, and working memory.

University students from the Bronx, NY (N=50, mean age = 19.8, female = 78.4%) completed the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ). Estimated intellectual ability was assessed using the Wechsler Test of Adult Reading (WTAR). Cognitive assessment included the Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test (attention and executive function) and the Cogstate battery (Groton Maze Learning Test (executive function), Chase Test (processing speed), Identification Test (attention), One Back Test (attention), and Two Back Test (working memory)). Psychosocial assessment included the Perceived Stress Scale (PSS), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI).

A series of general linear models were used to determine the relationship between RBD symptoms and cognition. Race/ethnicity, depressive symptoms, and estimated intellectual ability were included as covariates. Using a cutoff score of five (range: 0-13) on the RBDSQ, the ANCOVAs determined that there was no association between RBD symptoms and the cognitive domains of attention, processing speed, executive function, and working memory. However, there was a trend for attention as measured by the Identification task (F(1,41) = 3.85, p = 0.057). Interestingly, Pearson’s chi-square test revealed that the relationship between depressive symptoms and RBD symptoms was significant (x2 = 6.87, p = 0.009). Those who had high RBD symptoms were more likely to have high depressive symptoms.

Our analyses indicated that in healthy young adults, RBD symptoms are not associated with the cognitive domains of attention, processing speed, executive function, or working memory. However, there may be a trend for attention, which warrants further research with a larger sample size. Of interest, young adults with RBD symptoms were more likely to have clinically significant depressive symptoms. Given that RBD in older adults is associated with incident dementia with Lewy body and Parkinson’s disease, which are associated with cognitive decline and depression, further work is necessary to explore the mechanisms of this connection as well as the development of clinical disorders.

Obstructive sleep apnea (OSA) has been associated with cognitive deficits as evidenced by neuropsychological testing in the domains of attention/working memory, verbal memory, processing speed, and executive function. OSA is often comorbid with hypertension and has been considered a risk factor for hypertension (Kareem et al., 2018; Tietjens et al., 2019). Both hypertension and OSA have been shown to be independent predictors of memory (Kinoshita et al., 2012). OSA and posttraumatic stress disorder (PTSD) are also frequently co-occurring, especially among veterans. In a group of veterans with a history of PTSD, we seek to explore the effects of sleep apnea and hypertension on cognitive functioning, particularly auditory learning/memory.

One hundred and three male and female participants with comorbid OSA and PTSD symptomology were screened as part of a larger VA Palo Alto Health Care System study. Participants (age: x=56.3, a=13.8, 24-81 years; education: x=14.6, a=2.3, 8-20 years; 9.6% female, 89.6% male) completed a neuropsychological battery, including the CVLT-II and WMS-IV Logical Memory. Presence or absence of hypertension was dichotomously coded and AHI severity was categorically coded. An auditory learning/memory composite variable was created using the z-score transformation method (Dodge et al., 2020). Variables and covariates were entered into a hierarchical regression.

The initial regression model revealed hypertension and OSA severity to be independent predictors of performance on auditory learning/memory (hypertension: ß= -0.71, p<0.01; OSA: ß= -0.42, p<0.01), where presence of hypertension or increased severity of OSA resulted in worse performance on the auditory learning/memory composite.

Results suggest that hypertension and OSA may independently and negatively affect performance on measures of auditory learning/memory in veterans with PTSD symptomology and OSA. Such findings underscore the importance of assessing and treating both hypertension and OSA among veterans with PTSD to improve not only physical health, but also cognitive health. Further research demonstrating similar findings is recommended along with studies investigating whether or not the treatment of hypertension and OSA can improve auditory learning/memory.

Chronic insomnia is a highly prevalent disorder affecting approximately one-in-three Americans. Insomnia is associated with increased cognitive and brain arousal. Compared to healthy individuals, those with insomnia tend to show greater activation/connectivity within the default mode network (DMN) of the brain, consistent with the hyperarousal theory. We investigated whether it would be possible to suppress activation of the DMN to improve sleep using a type of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS).

Participants (n=9, 6 female; age=25.4, SD=5.9 years) meeting criteria for insomnia/sleep disorder on standardized scales completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of laboratory monitored sleep on separate weeks. Each session included two resting state functional magnetic resonance imaging (fMRI) sessions separated by a brief rTMS session. Stimulation involved a 40 second cTBS stimulation train applied over an easily accessible cortical surface node of the DMN located at the left inferior parietal lobe. After scanning/stimulation, the participant was escorted to an isolated sleep laboratory bedroom, fitted with polysomnography (PSG) electrodes, and allowed an 8-hour sleep opportunity from 2300 to 0700. PSG was monitored continuously and scored for standard outcomes, including total sleep time (TST), percentage of time various sleep stages, and number of arousals.

Consistent with our hypothesis, a single session of active cTBS produced a significant reduction of functional connectivity (p < .05, FDR corrected) within the DMN. In contrast, the sham condition produced no changes in functional connectivity from pre- to post-treatment. Furthermore, after controlling for age, we also found that the active treatment was associated with meaningful trends toward greater overnight improvements in sleep compared to the sham condition. First, the active cTBS condition was associated with significantly greater TST compared to sham (F(1,7)=14.19, p=.007, partial eta-squared=.67). Overall, individuals obtained 26.5 minutes more sleep on the nights that they received the active cTBS compared to the sham condition. Moreover, the active cTBS condition was associated with a significant increase in the percentage of time in rapid eye movement (REM%) sleep compared to the sham condition (F(1,7)=7.05, p=.033, partial eta-squared=.50), which was significant after controlling for age. Overall, active treatment was associated with an increase of 6.76% more of total sleep time in REM compared to sham treatment. Finally, active cTBS was associated with fewer arousals from sleep (t(8) = -1.84, p = .051, d = .61), with an average of 15.1 fewer arousals throughout the night than sham.

Overall, these findings suggest that this simple and brief cTBS approach can alter DMN brain functioning in the expected direction and was associated with trends toward improved objectively measured sleep, including increased TST and REM% and fewer arousals during the night following stimulation. These findings emerged after only a single 40-second treatment, and it remains to be seen whether multiple treatments over several days or weeks can sustain or even improve upon these outcomes.

Cognitive decline is expected in normative aging (Cabeza et al., 2018; Salthouse, 2019), which can lead to impairments in adaptive functioning (Yam et al., 2014). Several cognitive domains have been associated with adaptive functioning in older adult samples, including processing speed and executive functioning (e.g., Nguyen et al., 2019; Vaughn & Giovanello, 2010). A recent study examining a mixed clinical sample of older adults demonstrated that processing speed was more predictive of functional decline than other cognitive domains, including aspects of executive functioning (Roye et al., 2022). Therefore, this study attempts to build on previous findings by further examining the relationships between processing speed, adaptive functioning, and executive functioning. Specifically, it investigated the extent to which processing speed mediated the associations between executive functioning and adaptive functioning.

Participants (N = 239) were selected from a clinical database of neuropsychological evaluations. Inclusion criteria were age 60+ (M = 74.0, SD = 6.9) and completion of relevant study measures. Participants were majority White (93%) women (53.1%). Three cognitive diagnosis groups were coded: No Diagnosis (N = 82), Mild Neurocognitive Disorder (NCD; N = 78), and Major NCD (N = 79). The Texas Functional Living Scale (TFLS) was used as a performance-based measure of adaptive functioning. Processing speed was measured using the Coding subtest from the Repeatable Battery for the Assessment of Neuropsychological Status. Executive functioning performance was quantified using part B of the Trail Making Test, Controlled Oral Word Association Test, and Similarities and Matrix Reasoning subtests from the WAIS-IV and WASI-II. Mediation models included age and years of education as covariates and indirect effects were assessed with bootstrapped confidence intervals (Hayes, 2020).

Processing speed mediated all measures of executive functioning. The pattern was consistent for all executive functioning measures such that poorer executive functioning was associated with poorer processing speed, which was subsequently associated with poorer adaptive functioning. Direct effects were significant for all models (ps < .03), suggesting that executive functioning maintained unique associations with adaptive functioning. Follow-up analyses indicated no evidence for moderation of the mediation models based on diagnostic group.

These results highlight the importance of processing speed in understanding real-world implications of pathological and non-pathological cognitive aging. Processing speed mediated all relationships between executive functioning and adaptive functioning. There was no evidence for moderation of these effects, supporting generalizability regardless of neurocognitive disorder and etiologic subtype. Further investigation is warranted into the importance of processing speed in explaining associations of other cognitive domains with adaptive functioning.

Functional disability is a foreseeable consequence of neurodegenerative diseases affecting cognition, yet there are few validated instruments that assess functional capacity for use in pre-clinical and clinical dementia conditions. To our knowledge, the existing instruments do not comprehensively assess decision-making capacity across the numerous functional domains of daily life. We developed and evaluated the utility of an informant-report measure, the Assessment of Functional Capacity Interview (AFCI), within a sample of cognitively unimpaired and preclinical dementia groups.

Based on a comprehensive literature review, analysis of existing measures, and clinical experience, we generated >40 items consisting of open-ended questions assessing crucial aspects of daily functioning. These items were presented to 12 experts in the field of geriatrics and neuropsychology, through a graded approach (4 rounds of feedback and alterations), resulting in item modification or rejection, as well as addition of new items. The remaining items were piloted on three informants at the time of outpatient clinical evaluations, leading to further item refinement. The final version of the AFCI evaluated capacity across domains of financial affairs and management, medical affairs and healthcare management, home and personal safety, and social behaviors and community functioning. The AFCI contained 6 items per domain with response items that ranged from 0=no difficulty to 3=severe difficulty (scores ranged from 0 to 72).

Participants (N = 58; Agemean = 76; Educationmean = 16) were classified as cognitively unimpaired (CU, n = 17), subjective cognitive decline (SCD, n = 24), or mild cognitive impairment (MCI, n = 17) based on established criteria. All participants had a knowledgeable informant who completed the AFCI. We found statistically significant moderate to large correlations between the AFCI total score and an informant report measure of cognitive functioning (Brief Informant Form of Neurobehavioral Symptomatology total score), rs(42) = .73, p < .001, Test of Practical Judgment-informant total score rs(42) = .87, p < .001, and Montreal Cognitive Assessment total score rs(41) = -.34, p = .027. A Kruskal-Wallis H test revealed significant differences in AFCI total score between the three diagnostic groups, H(2) = 12.30, p = .002. Pairwise post-hoc analysis with Bonferroni correction showed a significant difference between CU and MCI (p = .001). The difference in AFCI total score between SCD and MCI was in the expected direction, but did not achieve statistical significance with correction, (p = .068). As expected, there was no statistically significant difference between CU and SCD (p =.353).

In this pilot sample (data collection is ongoing), the AFCI showed promise as a brief, clinically useful functional capacity instrument that is easily administered during a clinical interview or completed by knowledgeable informants. Results can help identify compromised decision-making in at-risk older adults to aid the prevention of common safety issues within this vulnerable population. Ongoing research will extend preliminary investigation of validity and further inform the utility of AFCI in both diagnostic and interventional contexts

A systematic approach is vital for adapting neuropsychological tests developed and validated in western monocultural, educated and English-speaking populations. However, rigorous and uniform methods are often not implemented during adaptation of neuropsychological tests and cognitive screening tools across different languages and cultures. This has serious clinical implications. Our group has adapted the Addenbrooke’s Cognitive Examination (ACE) III for the Bengali speaking population in India. We have taken a 'culture-specific’ approach to adaptation and illustrate this by describing the process of adapting the ACE III naming sub-test, with a focus on the process of selecting culturally appropriate and psychometrically reliable items

Two studies were conducted in seven phases for adapting the ACE III naming test. Twenty-three items from the naming test in the English and the different Indian ACE-R versions were administered to healthy Bengali speaking literate adults to determine image agreement, naming and familiarity of the items. Eleven items were identified as outliers. We then included 16 culturally appropriate items that were semantically similar to the items in the selected ACE-R versions of which 3 were identified as outliers. The final corpus consisting of 24 items was administered to 30 patients with mild cognitive Impairment, Alzheimer’s disease and vascular dementia, and 60 healthy controls matched for age and education to determine which items in the corpus best discriminated patients and the controls, and to examine their difficulty levels.

The ACE III Bengali naming test with an internal consistency of .76 included 12 psychometrically reliable, culturally relevant high naming-high familiarity and high naming-low familiarity living and non-living items. Item difficulty ranged from .47 to .88 and had discrimination indices >.44.

A key question for test development/adaptation is whether to aim for culture-broad or culture-specific tests. Either way, a systematic approach to test adaption will increase the likelihood that a test is appropriate for the linguistic/cultural context in which it is intended to be used. Adaptation of neuropsychological tests based on a familiarity driven approach helps to reduce cultural bias at the content level. This coupled with appropriate item selection statistics helps to improve the validity of the adapted tests and ensure cross-cultural comparability of test scores both across and within nations.

Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) play an essential role in the clinical evaluation of neuropsychological functions. Despite the extensive investigations of the MoCA in English speaking countries as well as emerging adaptation work in a few Asian cultures, evidence base for the utility of the Vietnamese MoCA (MoCA-V) is lacking. This has posed a huge challenge for current and future clinical practice in Vietnam, as the country continues to assume a large burden of brain-related disorders. This study examined the construct validity of the MoCA-V and identified a cut-off score for the determination of cognitive impairment in a prevalent neurological condition in Vietnam - traumatic brain injury (TBI).

Participants included 129 neurologically healthy individuals and 80 patients with moderate-to-severe TBI. All participants completed the MoCA-V, along with other common neurocognitive measures such as the Trail Making Test (TMT) Parts A and B, Vietnamese Verbal Fluency Test, and Digit Span.

Pearson’s correlations revealed significant, moderate correlations between performance on the MoCA-V subdomains and more comprehensive cognitive measures. Performance on the MoCA-V Attention domain was correlated with both Digit Span Forward, r(110) = .453, p < .001] and Digit Span Backward, r(110) = .303, p = .001; performance on the MoCA Language domain was correlated with the Vietnamese Verbal Fluency Test, r(107) = .334, p < .001; and performance on the MoCA Executive Function domain was correlated with the TMT-B, r(108) = -.479, p = .022. Performance on the MoCA-V was also associated with age, r(127) = -.659, p < .001, and education, r(127) = .769, p < .001, consistent with the general effects of age and education in cognitive abilities. Finally, a cut-off score of 22.5 was identified for the detection of cognitive impairment in Vietnamese people with TBI (AUC = 0.811; 95% CI = .75-.87, p < .001).

This study provides the first evidence for the construct validity and clinical utility of the MoCA-V. Future research is necessary to cross-validate study findings among other clinical populations. Lessons learned from neuropsychological test translation and adaptation process will be discussed, particularly in the development of the administration materials and test instructions (e.g., considerations for individuals with limited formal education, influences of colonialism in the development of test stimuli).

Visuospatial skills are frequently assessed with drawing tests. Research has suggested that the use of drawing tasks in low educated groups may lack the ability to discriminate healthy individuals from clinical populations. The aims of this study were to investigate the validity of visuoconstructional tests in a sample of older Greek Australian immigrants and compare their performances to a matched sample of patients with Alzheimer’s disease (AD).

We assessed visuoconstructional performances in a sample of 90 healthy older Greek Australians, with a primary school level of education, and compared performances to a demographically matched sample of 20 Greek Australians with a diagnosis of AD on four visuoconstructional drawing tests: Greek cross, four-pointed star, intersecting pentagons, and the Necker Cube.

While healthy participants tended to outperform the AD group on most copy tasks, high fail rates within the healthy sample were observed for the intersecting pentagons and Necker cube (78% and 73% fail rates respectively) when using established clinical cutoff scores. High rates of curved angle, omission, distorted relation between elements, spatial disorganization and three-dimensional design errors were found across the four-pointed star, intersecting pentagons, and the Necker cube in both healthy participants and those with AD. Exploratory receiver operating characteristic curve analysis revealed that, with perhaps the exception of the Greek cross, meaningful sensitivity and specificity could not be reached for the four-pointed star, intersecting pentagons, and Necker cube.

Cognitively healthy immigrants with low education appear to be at a disadvantage when completing visuoconstructional drawing tests, as their performance may be misinterpreted as indicating cognitive impairment. Future research is needed to identify alternative approaches to assess visuoconstructional ability in low education older cohorts.

The world’s 8 billion people speak about 7000 languages; 3.2 billion of those people natively speak the top 10 languages. Currently neuropsychology is moderately well-developed in 6 of the top 10 languages, serving roughly 2.5 billion. Developing robust neuropsychology in all 7000 languages to serve everyone equitably in their native language seems impractical within the next few decades. However, 1-2 billion people speak a major language as their second language so a pragmatic strategy may be to develop an alternative approach of second-language neuropsychology (SLN) to serve clients who speak rare languages natively but widely-diffused languages as their second language. This strategy involves adapting all levels of neuropsychological services to the second language user.

Intended participants are those who speak a language of limited (e.g., <1 million speakers) diffusion as their first language and a language of wider diffusion (historically-colonial languages such as English, Russian, Mandarin, or Arabic; regional trade languages such as Swahili or Lingala; or nationalized languages such as Indonesian or Tagalog) as their second or more language. Intended participants are those with Basic Interpersonal Communication Skills (BICS) in their second language, but not necessarily Cognitive and Academic Language Proficiency (CALP). SLN will adapt current neuropsychology techniques in the following domains:

1. 1. Oral language: interview, feedback, treatment, and communication among professionals;

2. 2. Detailed language use evaluation;

3. 3. testing and norms;

4. 4. written materials: reports, client education materials, treatment materials, professional education materials, etc.

The language style for such communication will use standard versions of such traditional or national languages, as commonly taught as a second language. It will use basic vocabulary, simple grammatical structures, and broadly-understood cultural referents. It will minimize grammatical complexity, slang, regionalisms, figures of speech, and metaphor. Materials will be available in the specified language both for those who are literate and for those with inadequate literacy. The development of such language style will require both written materials and training of neuropsychologists and allies. Once core SLN materials are developed, these may be further localized for specific communities to contribute to acceptance and effectiveness. These general strategies will need modification to the specifics of each major language, writing system, and population. This will be particularly true for testing language functioning itself, a particular challenge for the SLN strategy. The SLN strategy will require empirical verification of its viability in each major language and population. Some may perceive SLN as neo-colonialist and culturally insensitive; this may be mitigated in part through diversifying the neuropsychology workforce, community-based research, piloting, focus groups, and localization of materials.

Because this is a proposal and not yet a research project, prototype neuropsychological screening protocols for English-as-a-Second-Language and Spanish-as-a-Second-Language will be presented as examples.

Cultural and linguistic diversity present major challenges to providing equitable neuropsychological services to the world’s population. Current neuropsychology resources are least accessible to major populations that may be most in need. The SLN strategy is not perfect or universal but may reach the next 1-2 billion underserved population

Physical, sensory, and cognitive function are all related to successful aging, quality of life, and independence in older age. Decline in cognitive function, in particular, can create difficulty in many Instrumental Activities of Daily Living such as driving and other aspects of everyday function. Loss of driving competence can subsequently lead to depression, isolation, loss of independence and reduced quality of life. Results from a large randomized controlled trial investigating the long-term impact of Speed of Processing Training will be presented demonstrating the impact of such training on cognitive and everyday function. Speed of Processing Training is an adaptive cognitive intervention administered on a computer that improves visual attention, and has been shown to enhance the connections needed for visual attention using task-driven and resting state fMRI.

The ACTIVE clinical trial recruited a volunteer sample of 2,832 community dwelling older adults between the ages of 65 and 94 years at six different field sites in six different states. This study evaluated the impact of three cognitive interventions targeted at improving cognitive and everyday function which served as contract control conditions for each other. Participants were randomly assigned to speed of processing training, reasoning training, memory training, or a no-contact control group. Follow-up testing was collected in person for ten years, and at twenty years final archival data was collected from the Departments of Motor Vehicles at each of the six field sites, as well as the Medicare/Medicaid data across the twenty years since enrollment. Outcomes included measures of cognitive function, measures of IADL (including crash involvement and driving cessation), and secondary outcomes of mobility (falls, driving habits, life space), quality of life, mortality and health conditions (from Medicare Records).

Results will be presented with respect to everyday function including several longitudinal measures of mobility: number of miles driven per year and driving difficulty, rates of driving cessation, and crash involvement. Random effects modelling, cox proportional hazards, and rate ratios will be presented illustrating the positive impact of cognitive training on these outcome measures. In particular, Speed of Processing Training was found to sustain driving competence with respect to continued driving relative to other types of training, and to reduce the risk of crash involvement over ten years. Furthermore, decline in Speed of Processing was the only cognitive measure predictive of crash involvement longitudinally in the no-contact control group. Positive benefits were also observed for Health Related Quality of Life (HRQoL), and depression.

The ACTIVE clinical trial, among other studies, has demonstrated that cognitive training can have long-term positive benefit on the everyday abilities, quality of life, and continued independence of older adults.

Cognitive impairment is observed in up to two-thirds of persons with Multiple Sclerosis (MS). Impairments in cognitive processing speed (PS) is the most prevalent cognitive disturbance, occurs early in the course of disease and is strongly associated with disease progression, various brain parameters and everyday life functional activities. As such, cognitive rehabilitation for PS impairments should be an integral part of MS treatment and management. The current study examines the efficacy of Speed of Processing Training (SOPT) to improve processing speed (PS) in individuals with Multiple Sclerosis (MS). SOPT was chosen because of its significant positive results in the aging populations.

This double-blind, placebo-controlled randomized clinical trial included 84 participants with clinically definite MS and impaired PS, 43 in the treatment group and 41 in the placebo control group. Outcomes included changes in the Useful Field of View (UFOV) and neuropsychological evaluation (NPE) including measure of PS (e.g., Pattern Comparison and Letter Comparison). Participants completed a baseline NPE and a repeat NPE post-treatment. Treatment consisted of 10 sessions delivered twice per week for 5 weeks. After the 5 weeks, the treatment group was randomized to booster sessions or no contact. Long-term follow-up assessments were completed 6 months after completion of treatment. The primary outcome were tests of PS including UFOV and neuropsychological testing.

A significant effect of SOPT was observed on both the UFOV (large effect) and Pattern Comparison with a similar pattern of results noted on Letter Comparison, albeit at a trend level. The treatment effect was maintained 6-months later. The impact of booster sessions was not significant. Correlations between degree of improvement on the UFOV and the number of levels completed within each training task were significant for both Speed and Divided Attention indicating that completion of more levels of training correlated with greater benefit.

SOPT is effective for treating PS deficits in MS with benefit documented on both the UFOV and a neuropsychological measure of PS. Less benefit was observed as the outcome measures became more distinct in cognitive demands from the treatment. Long-term maintenance was observed. The number of training levels completed within the 10-sessions exerted a significant impact on treatment benefit, with more levels completed resulting in greater benefit.

CI Cognitive Therapy (CICT) is a combination of behavioral techniques derived from CI Movement Therapy (CIMT) modified to apply to the cognitive domain, and Speed of (Cognitive) Processing Training (SOPT). SOPT is effective in improving cognitive function in the treatment setting and driving ability in everyday situations. The data concerning the effect of SOPT on other cognition-based instrumental activities of daily living (IADL) in everyday situations is incomplete. The strengths of CIMT, based on its Transfer Package (TP), are to facilitate 1) transfer of improved function from the treatment setting to IADL in everyday settings, and 2) long-term retention of the improved performance of IADL. This study sought to determine in a preliminary case series whether the TP of CI Movement Therapy combined with SOPT would have the same effect on a wide range of impaired cognition-based ADL.

Participants were 6 adults with chronic stroke: mean chronicity = 36.2 months, (range, 16-56 months); mean age = 59.7 years, (range, 47-55); 1 female; 3 African American and 3 European American. Five had mild cognitive impairment, while one had moderate impairment. Participants received 35 hours of outpatient treatment in 10-15 sessions distributed over 2-6 weeks, depending on the participants’ availability. Sessions began with 1 hour of SOPT training followed by training of cognition-based ADL by the process of shaping, a common method in the behavior analysis field. Other behavior analysis methods employed in the TP of CI Movement Therapy were used, including: 1) behavior contracting, daily assignment of homework, participation of a family member in the training and monitoring process, daily administration of a structured interview assessing amount and quality of performance of 30 IADL, problem solving to overcome perceived (or real) barriers to performance of IADL. Participants were given daily homework assignments in follow-up and were contacted in periodic, pre-arranged phone calls to determine status, compliance and problem-solve.

All six participants showed marked improvement on the SOPT test similar to that in the Ball et al studies. However, here transfer to IADL outside the treatment setting was substantial. On the main real-world outcome, the Canadian Occupational Performance Measure (COPM), there were increases of 2.7±1.3 and 2.1±1.6 on the two scales (d’s = 1.9 & 1.3, respectively). (Changes on the COPM > 2 points are considered clinically meaningful and changes in d’ >.8 are considered large). On two other real-word measures, the Cognitive Task Activity Log (CTAL) and inventory of Improved and New Cognitive Activities (INCA), there was a marked increase during the acquisition phase of training. There was no loss in retention over the 6-16 months (mean = 12.2) of follow-up to date. Instead, the INCA showed strong further improvement after the end of treatment-setting training, especially in the New Activities Not Performed Since Before Stroke Onset category, going from a mean of 8.2 after training to 14.6 at the end of follow-up.

These very preliminary results suggest that CICT may be an efficacious therapy for mild to moderate cognitive impairment in chronic stroke and possibly other disorders.

Persistent brain fog is common in adults with Post-Acute Sequelae of SARS-CoV-2 infection (PASC), in whom it causes distress and in many cases interferes with performance of instrumental activities of daily living (IADL) and return-to-work. There are no interventions with rigorous evidence of efficacy for this new, often disabling condition. The purpose of this pilot is to evaluate the efficacy, on a preliminary basis, of a new intervention for this condition termed Constraint-Induced Cognitive therapy (CICT). CICT combines features of two established therapeutic approaches: cognitive speed of processing training (SOPT) developed by the laboratory of K. Ball and the Transfer Package and task-oriented training components of Constraint-Induced Movement therapy developed by the laboratory of E. Taub and G. Uswatte.

Participants were > 3 months after recovery from acute COVID symptoms and had substantial brain fog and impairment in IADL. Participants were randomized to CICT immediately or after a 3-month delay. CICT involved 36 hours of outpatient therapy distributed over 4-6 weeks. Sessions had three components: (a) videogamelike training designed to improve how quickly participants process sensory input (SOPT), (b) training on IADLs following shaping principles, and (c) a set of behavioral techniques designed to transfer gains from the treatment setting to daily life, i.e., the Transfer Package. The Transfer Package included (a) negotiating a behavioral contract with participants and one or more family members about the responsibilities of the participants, family members, and treatment team; (b) assigning homework during and after the treatment period; (c) monitoring participants’ out-of-session behavior; (d) supporting problem-solving by participants and family members about barriers to performance of IADL; and (e) making follow-up phone calls. IADL performance, brain fog severity, and cognitive impairment were assessed using validated, trans-diagnostic measures before and after treatment and three months afterwards in the immediate-CICT group and on parallel occasions in the delayed-CICT group (aka waitlist controls).

To date, five were enrolled in the immediate-CICT group; four were enrolled in the wait-list group. All had mild cognitive impairment, except for one with moderate impairment in the immediate-CICT group. Immediate-CICT participants, on average, had large reductions in brain fog severity on the Mental Clutter Scale (MCS, range = 0 to 10 points, mean change = -3.7, SD = 2.0); wait-list participants had small increases (mean change = 1.0, SD = 1.4). Notably, all five in the immediate-CICT group had clinically meaningful improvements (i.e., changes > 2 points) in performance of IADL outside the treatment setting as measured by the Canadian Occupational Performance Measure (COPM) Performance scale; only one did in the wait-list group. The advantage for the immediate-CICT group was very large on both the MCS and COPM (d’s = 1.7, p’s < .05). In follow-up, immediate-CICT group gains were retained or built-upon.

These preliminary findings warrant confirmation by a large-scale randomized controlled trial. To date, CICT shows high promise as an efficacious therapy for brain fog due to PASC. CICT participants had large, meaningful improvements in IADL performance outside the treatment setting, in addition to large reductions in brain fog severity.

Interpretation of neuropsychological (NP) tests depends on the quality of the normative standards available for the tests. Co-norming across tests is necessary when interpreting differences between scores on different tests. The relevance of specific norms for an individual examinee further depends on multiple design features of the standardization studies, including: when the studies were conducted, sampling strategy, inclusion/exclusion criteria, age, sex/gender, education, race and ethnicity, socioeconomic status, and region. This paper examines the standardization studies of the most widely used NP tests, identifies their strengths and weaknesses, and makes recommendations for interpretive caveats based on these analyses.

We reviewed the standardization strategies and coded information about the sampling frames, inclusion/exclusion criteria, stratification methods, demographic characteristics, and sample sizes overall and within each stratum where relevant. These methods were applied to the WAIS-IV, WMS-IV, CVLT3, D-KEFS, Pearson Advanced Clinical Solutions (ACS), Rey Complex Figure Test, WCST, Symbol Digit Modalities Test, RBANS, BVMT-R, HVLT, Halstead-Reitan (“Heaton et al”) Norms for Boston Naming, Finger Tapping, Grooved Pegboard), MOANS, and MOAANS (Boston Naming, Trail Making Test, Judgement of Line Orientation). We calculated multiple indexes for each test, including standard errors and confidence intervals for scaled scores.

Most tests used age only as a stratification factor, providing “age corrected” scores for selected age bands. The sample sizes for the age strata range from 1 to ∼200 but were usually less than 100 participants/stratum. Sex differences were rarely reported and some studies had markedly uneven distributions of sex. Education was not used as a stratification factor in any study, and few norms attempted corrections for education. The possible interactions of age and education on test scores are seldom reported and cell sizes for combinations of age and education may be too small to enable robust estimates of scores, especially at lower levels of education and older ages. The possible impact of race and ethnicity are rarely interrogated except in ACS, Heaton and MOAANS norms, which all focus on “African American” participants. Discrepancies in scores across ACS, Heaton and MOAANS suggest marked sampling differences.

Existing norms have major limitations which may impact the clinical assessment of individuals and result in inappropriate treatment recommendations as well as lead to inappropriate classification in clinical trials, which may include score “cutoffs” based on widely used normative standards. Most norms use only age as a stratification factor, despite robust impacts of education on scores. Race and ethnicity are poorly represented, fail to reflect current demographic characteristics of the United States, and existing norms present major conflicts for African American groups, with the same raw scores differing by a full standard deviation depending only on the source of normative data. Sex differences are examined infrequently and it remains unclear to what extent sex or gender differences may affect some scores. There is an urgent need for new, preferably “dynamic” normative standards, that include sampling by socially and demographically meaningful metrics, to provide greater precision in assessment of neuropsychological scores and score discrepancies, and for evaluating the inclusion/exclusion criteria, and criteria for efficacy in clinical trials that use neurocognitive endpoints.

There is a dearth of an appropriate standardized tool to assess neuropsychological functions in rural population, which has low literacy rates, are culturally diverse, and have limited access to healthcare resources. The NIREH Neuropsychological Battery for Rural Population (NINB-RP) is a relatively brief and easy-to-administer battery comprising multiple tests that are modified or adopted as per rural community settings to evaluate verbal learning, fine coordination, attention efficiency, executive task, concentration, and visual attention, mental flexibility, and motor coordination in rural populations. The present study aimed to examine the clinical validity and establish cut-off scores for impairment of neuropsychological functions for different age, gender, and education levels of NINB-RP in a rural community in central India.

This was a prospective cross-sectional study conducted in participants aged > 18 years (n=2952, M: F=1407:1545) recruited through a stratified sampling technique from 23 randomly selected villages from central India. The data of nine neuropsychological tests [(Finger and Tweezer dexterity test (FDT, TDT); Digit Forward and Backward test (DFT, DBT); Serial subtraction test (SST); Trail Making-A and B; Finger Tapping test (FTT); and Letter Digit Substitution test, LDST)] from 215 cognitively impaired and 2737 healthy control subjects were analyzed. The tests were performed in a village school/community hall or an outdoor camp. Independent sample t-test, Chi-square test, and Receiver Operating Characteristic (ROC) curve were used to calculate the area under the curve (AUC), cut-off scores, and sensitivity (ST)/specificity (SP) values for seven conditions, i.e., gender (male vs. female), age groups (up to 49 years and above 50 years); and educational levels (illiterate, intermediate and college). For those variables where ST/SP values were lower than 0.70, a unique cut-off score was calculated for the entire sample, adjusting by age and educational levels.

A significant difference in mean (median) scores between the healthy control and cognitively impaired groups were observed in all tests except Trail Making A and B and LDST. The AUC for most of the tests ranged from 0.70 to 0.81, and the ST/SP values ranged from 69-73% and 65-75%, respectively. The results showed that most tests of NINB-RP reached moderate to good sensitivity and specificity for gender, age and education levels, except for DBT for females, above 50 years, and illiterate and intermediate education groups. FDT for males [AUC: 0.85 (95%CI0.80-0.91], ST/SP=76/82%] and females [(AUC=0.78 (95%CI0.74-0.82), ST/SP=71/70%], TDT for intermediate education group [AUC=0.82 (95%CI0.60-1.00), ST/SP=86/83%] and FTT for less than 49 years age group [AUC=0.75 (95%CI0.67-0.84), ST/SP=71/76%] were the most useful tests to discriminate among healthy control and cognitively impaired rural population.

The present study is an attempt to establish the cut-off scores of a neuropsychological battery for a large rural population in the community setting. The proposed cut-off values might be helpful in clinical assessment in rural areas where clinical neuropsychology services are not readily available. NINB-RP can be a valuable tool for clinical research studies in rural communities. Further studies on similar samples in other countries need to be undertaken.