How do we measure attention? Using factor analysis to establish construct validity of neuropsychological tests

Vascular risk scores are associated with incident dementia. Information regarding their association with cognitive performance and decline in racially/ethnically diverse cohorts is lacking. In 4 392 Multi-Ethnic Study of Atherosclerosis participants (aged 60.1 ± 9.4 years; 53% women; 41% White, 11% Chinese American, 26% African American, 21% Hispanic), we compared associations of Exam 1 (2000-2002) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham Stroke Risk Profile (FSRP), and atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) risk scores with Exam 5 (2010-2012) Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive test performance using multivariable linear regression, and examined racial/ethnic interactions. In 1 838 participants with repeat CASI data at Exam 6 (2016-2018), we related risk scores to odds of a 1-SD decline in CASI performance using multivariable logistic regression. SD increments in each risk score were associated with worse cognitive performance. CAIDE had stronger associations with CASI performance than the FSRP and ASCVD-PCE, but associations of ASCVD-PCE with the DSC and DS were similar to CAIDE (difference in β [95% CI] = -0.57 [-1.48, 0.34] and -0.21 [-0.43, 0.01], respectively). Race/ethnicity modified associations. For example, associations between CAIDE and CASI were greater in African Americans and Hispanics than in Whites (difference in β = 0.69 [0.02, 1.36] and 1.67 [0.95, 2.39], respectively). Risk scores were comparably associated with decline in CASI performance. Antecedent vascular risk scores are associated with cognitive performance and decline in the 4 most common U.S. racial/ethnic groups, but associations differ among risk scores and by race/ethnicity.

In addition to episodic memory impairment, working memory may also be compromised in mild cognitive impairment (MCI) or Alzheimer's dementia (AD), but standard verbal and visuospatial span tasks do not always detect impairments.ObjectiveTo examine whether more complex verbal and visuospatial working memory tasks result in more reliable impairment detection.MethodsThe Digit Span (forward, backward and sequencing), Spatial Span (forward and backward) and Spatial Addition test from the Wechsler batteries were administered to MCI and AD patients and performance compared to healthy older adult controls.ResultsResults showed that both the MCI and AD patients had impaired performance on the Spatial Addition test. Both groups also had impaired performance on all three Digit Span conditions, but no differences were found between forward and backward conditions in any of the groups. The sequencing condition differed from the backward condition only in the AD group. Spatial Span performance was impaired in AD group patients but not in MCI patients.ConclusionWorking memory deficits are evident in MCI and AD even on standard neuropsychological tests. However, available tests may not detect subtle impairments, especially in MCI. Novel paradigms tapping the episodic buffer component of working memory may be useful in the assessment of working memory deficits, but such instruments are not yet available for clinical assessment.

Introduction Bipolar disorder in adolescents is often referred to as juvenile bipolar disorder. A peak in the prevalence of bipolar disorder has been documented between the ages of 15 and 19 years. Wide-ranging neuropsychological deficits have been found in many studies of juvenile bipolar disorder. Persistent neuropsychological deficits present in the euthymic state suggest that such deficits could be vulnerability trait markers of the illness. Aim To identify and assess cognitive functioning in euthymic adolescents diagnosed with bipolar disorder. Participants and methods A case–control cross sectional study, in which 30 euthymic bipolar adolescents were recruited from the psychiatric adolescent clinic of Kasr al Ainy and compared with 30 healthy controls. Psychometric procedure The Hamilton Rating Scale of Depression, the Young Mania Rating Scale, the letter cancellation test, the digit span and digit symbol/coding tests, the Bender gestalt test and the Wisconsin card sorting test were used. Results Cases had significantly higher mean scores than controls in the letter cancellation test and its omission errors as well as in the perseverative errors of the Wisconsin card sorting test, and lower mean scores in the digit span, digit symbol coding and the Bender gestalt tests. There was a significant positive correlation between the number of omission errors on the letter cancellation test and both of the number of manic episodes and the age of onset of the illness. Conclusion There are neuropsychological deficits in the areas of sustained attention, set shifting, processing speed and visual and auditory short-term memory in euthymic bipolar adolescent patients, type I. There is a significant correlation between the number of manic episodes as well as age of illness onset and sustained attention.

The purpose of this study was to determine the immediate effects of cognitive training on healthy older adults and verify the transfer effects of targeted and non-targeted abilities. The design consisted of a semi-randomized clinical controlled trial. The final sample was composed of 80 volunteers recruited from a Brazilian community (mean age = 69.69; SD = 7.44), which were separated into an intervention group (N = 47; mean age = 69.66, SD = 7.51) and a control group (N = 33; mean age = 69.73, SD = 7.45). Intervention was characterized by adaptive cognitive training with 12 individual training sessions of 60 to 90 minutes (once a week). Eight instruments were used to assess effects of cognitive training. Five were used to assess trained abilities (near effects), including: Memorization Tests (List and History), Picture Completion, Digit Span, Digit Symbol-Coding, and Symbol Search (the last four from WAIS-III). Two instruments assessed untrained abilities (far effects): Arithmetic and Matrix Reasoning (WAIS-III). The non-parametric repeated measures ANOVA test revealed a significant interaction between group by time interaction for Picture Completion [F(74) = 14.88, p = .0002, d = 0.90, CLES = 73.69%], Digit Symbol-Coding [F(74) = 5.66, p = .019, d = 0.55, CLES = 65.21%] and Digit Span [F(74) = 5.38, p = .02, d = 0.54, CLES = 64.85%], suggesting an interventional impact on these performance tasks. The results supported near transfer effects, but did not demonstrate a far transfer effects.

Although cognitive decline has previously been associated with mobility limitations and frailty, the relationship between sustained attention and gait speed is incompletely characterized. To better quantify the specificity of the sustained attention and gait speed association, we examined the extent to which this relationship is unique rather than accounted for by executive functioning and physical health characteristics. 58 middle-to-older-aged community-dwelling adults without overt evidence of cognitive impairment (45–90 years old; 21 females) participated in the study. Each participant completed a 4-meter gait speed assessment and validated neuropsychological tests to examine various domains of executive functioning including working memory (i.e., Digit Span), inhibitory control (i.e., D-KEFS Color-Word Interference), and task switching (i.e., D-KEFS Number/Letter Switching). Multiple physical and vascular risk factors were also evaluated. Sustained attention was assessed using the gradual onset continuous performance task (gradCPT), a well-validated go/no-go sustained attention task. A series of linear regression models were used to examine how different aspects of cognition, including sustained attention and traditional measures of executive functioning, related to gait speed while controlling for a variety of physical and vascular risk factors. Among all predictors, gradCPT accuracy explained the most variance in gait speed (R2 = 0.19, p < 0.001) and was the only significant predictor (β = 0.35, p = 0.01) when accounting for executive functioning and other physical and vascular risk factors. The present results indicate that sustained attention may be uniquely sensitive and mechanistically linked to mobility limitations in middle-to-older adults.

A - 76 Association between Sleep Apnea Risk and Cognitive Performance in Individuals with Type 1 Diabetes (T1D): Evidence from the Glucog Study.

Purpose: There isgrowing concern surrounding the harmful effects of soccer heading on cognitive function. The present study aims to examine the immediate effects of heading. Methods: 30 recreational male soccer players were divided into three groups that undertook 20 consecutive headers with a soft (8.8 psi), hard (16.2 psi), or no (control) ball. A battery of neuropsychological tests was completed before and after heading: King-Devick, trail-making (TM) (A, B), digit span (DS) and spatial span (SS) (forward, backward). Results: Significant increase in the time (M = 4.44 s) and errors (M = 1.45) for the King-Devick test within the hard and soft groups, although there was no significant difference for TM-A and TM-B. Significant decline for SS forward within the hard and soft groups (M= −16%), although the declines for SS backward (M = −16%), DS forward (M= −23%) and DS backward (M = −25%) were present only for the hard group (ps <.05). Discussion: While outside of regular match-play, this study showed that heading negatively influenced one indicator of a suspected concussion (King-Devick), as well as working memory (DS, SS) that is essential for daily life. These findings contribute to the growing debate surrounding heading safety.

BackgroundHypertension and diabetes are key modifiable risk factors for Alzheimer’s disease and related dementias. Research has typically focused on blood pressure (BP) levels, despite evidence that high BP variability (BPV) over time may predict poorer cardiovascular, neuropathological, and neurocognitive outcomes. We assessed associations between BPV and global cognition in a cohort of participants from the Multi‐Ethnic Study of Atherosclerosis (MESA), including 4 ethnoracial groups: White, African‐American, Chinese, and Hispanic.MethodsLongitudinal BP data across 6 MESA examinations were used in multivariable linear and logistic regression analyses to determine the association BPV and cognitive function, decline, and incident impairment. Two measures of long‐term BPV (Average Real Variability [ARV] and Variability Independent of the Mean [VIM]) and group‐based latent BP trajectories were estimated over an average of 9.4 years. The Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS), were administered at MESA Exams 5 and 6, an average of 6.3 years apart. This enabled the assessment of cognitive function, decline, and cognitive impairment, defined as performance in the lowest 10% of groups stratified by age, education, and race.ResultsParticipants (N=1314) had a mean baseline age of 57 years, and were 50% female and 48% White. Increased systolic and diastolic BPV were associated with poorer performance across all measures and with increased global cognitive decline in unadjusted models. Higher systolic (β = ‐0.06, P=0.05) and diastolic (β = ‐0.08, P=0.005) ARV was predictive of increased CASI decline after adjustment for demographic and clinical characteristics, including mean BP. Significant interactions and subsequent stratified analyses indicated that the strongest relationships between BPV and global cognition were in participants older than age 65, White or Black, APOE ε4 non‐carriers, males, and non‐antihypertensive medication users. Higher and more variable latent systolic and diastolic BP trajectories predicted reduced performance on the CASI, DS, or DSC tests before and after adjustment for clinical and demographic characteristics.ConclusionResults suggest high BPV is a risk factor for global cognitive dysfunction and decline, independent of mean BP levels, in this middle‐aged, healthy, and multi‐ethnic population. Relationships may differ across demographic, genetic, and clinical characteristics.

A placebo-controlled, partial cross-over, double-blind, randomized study was performed with 46 adults with sleep apnea-hypopnea syndrome (SAHS) to determine the effect of therapeutic and subtherapeutic (0-1 cm H(2)O) nasal continuous positive airway pressure (CPAP) treatment on polysomnographic and neuropsychological testing. The following neuropsychological tests were administered: Geriatric Depression Scale, Trail Making A and B, Digit Span Test Forward and Backward, Epworth Sleepiness Scale, SteerClear, Digit Symbol, Controlled Oral Word Association, and Complex Figure Recall. Compared with results without CPAP, subtherapeutic CPAP did not affect any measured polysomnographic parameter. Comparison of neuropsychological test results obtained between the initial periods of effective treatment (Group 1, 16.1 d; Group 2, 19.6 d; p = NS) in all subjects showed significant improvements in Digit Symbol, Digit Span Backward, and Complex Figure tests. However, there were no group differences in changes in test results during the period when one group was on effective CPAP and the other on ineffective CPAP (Group 1, 16.1 d; Group 2, 13.9 d; p = NS). The results indicate the feasibility and importance of using ineffective CPAP as a placebo treatment and the importance of including a placebo control in studies evaluating the effect of treatment on neuropsychological function in SAHS.

Pathological mental fatigue after mild traumatic brain injury (TBI-MF) is characterized by pronounced mental fatigue after cognitive activity. The neurological origin is unknown, and we aimed in the present study to investigate how prolonged mental activity affects cognitive performance and its neural correlates in individuals with TBI-MF. We recruited individuals with TBI-MF (n = 20) at least 5 months after injury, and age-matched healthy controls (n = 20). We used functional near-infrared spectroscopy (fNIRS) to assess hemodynamic changes in the frontal cortex. The self-assessed mental energy level was measured with a visual analog scale (VAS) before and after the experimental procedure. A battery of six neuropsychological tests including Stroop–Simon, Symbol Search, Digit Span, Parallel Serial Mental Operation (PaSMO), Sustained Attention and Working Memory test, and Digit Symbol Coding (DSC) were used. The sequence was repeated once after an 8 min sustained-attention test. The test procedure lasted 2½ h. The experimental procedure resulted in a decrease in mental energy in the TBI-MF group, compared to controls (interaction, p < 0.001, ηp2 = 0.331). The TBI-MF group performed at a similar level on both DSC tests, whereas the controls improved their performance in the second session (interaction, p < 0.01, ηp2 = 0.268). During the Stroop–Simon test, the fNIRS event-related response showed no time effect. However, the TBI-MF group exhibited lower oxygenated hemoglobin (oxy-Hb) concentrations in the frontal polar area (FPA), ventrolateral motor cortex, and dorsolateral prefrontal cortex (DLPFC) from the beginning of the test session. A Stroop and Group interaction was found in the left ventrolateral prefrontal cortex showing that the TBI-MF group did have the same oxy-Hb concentration for both congruent and incongruent trials, whereas the controls had more oxy-Hb in the incongruent trial compared to the congruent trial (interaction, p < 0.01, ηp2 = 0.227). In sum these results indicate that individuals with TBI-MF have a reduced ability to recruit the frontal cortex, which is correlated with self-reported mental fatigue. This may result both in deterioration of cognitive function and the experience of a mental fatigue after extended mental activity.

Context/Objective: Cognitive deficits can impact as many as 60% of individuals with spinal cord injury (SCI). In an effort to identify the nature of cognitive deficits in SCI, we examined neuropsychological test performance in individuals with SCI, age matched healthy controls and older healthy controls.Design: Participants completed a motor-free neuropsychological test battery assessing attention, working memory, information processing speed, new learning /memory and executive control.Setting: Outpatient rehabilitation research facility.Participants: Participants included 60 individuals with chronic spinal cord injury [SCI; 32 with paraplegia (T2-T12) and 28 with tetraplegia (C3-T1)], 30 age-matched healthy controls (AMHC; 30–40 years old) and 20 older healthy controls (OHC; 50–60 years old).Outcome Measures: Wechsler Intelligence Scale – 3rd edition (WAIS-III) Digit Span and Letter-Number Sequencing; Symbol Digit Modalities Test (SDMT) – oral version; California Verbal Learning Test-II; Paced Auditory Serial Addition Test (PASAT); Wechsler Abbreviated Scale of Intelligence (WASI); Delis-Kaplan Executive Function System; Verbal Fluency subtest.Results: Significant differences were noted between the SCI and AMHC groups on measures of information processing speed, new learning and memory, and verbal fluency. No significant differences were noted between the groups on tests of attention or working memory.Conclusion: The current study documented differences in specific realms of cognitive functioning between a chronic SCI sample and AMHC. Implications for cognitive rehabilitation and overall quality of life are discussed. Additional research is needed utilizing a more comprehensive battery of motor-free neuropsychological tests that avoid the confound of upper limb motor limitations on cognitive performance.

Introduction: The diagnosis of vascular cognitive impairment relies on bedside tools to quantify the degree of disease burden. Given the critical importance of implementing early interventions, it is becoming increasingly important to investigate more sensitive and easily administered tools for accurately characterizing these deficits. Hypothesis: The current study aims to evaluate the effectiveness of using Miro, a tablet-based mobile application, developed by The Cognitive Healthcare Company, designed to measure the same cognitive domains as traditional pencil-and-paper tests but (1) require less administration time; (2) provide reliable scoring; (3) offer greater ease of use; and (4) capture and analyze informative data, like speech, fine motor function and eye movements, that are not typically used in clinical settings. Methods: Subjects were recruited from the Stroke and Cognitive Disorders Clinic. Subjects were randomized to undergo pencil-and-paper or iPad testing first. The battery of tests in each medium take roughly 60 minutes to complete. In this ongoing study, there will be 3 total participant visits over one year, to evaluate rate of decline or improvement in each medium. Results: 11 subjects have been enrolled in the study thus far. These subjects have a mean age of 64.6 ± 9.48 and years of education 16.3 ± 2.61.There were strong Spearman rho correlations between pencil and paper testing and iPad testing on digit span forwards (0.848, p &lt; 0.002), digit span backwards (0.946, p &lt; 0.001), symbol digit coding (0.936, p &lt; 0.001), Trails A and B (0.794, p &lt; 0.006). When asked to rate their preference on a 7-point Likert scale (1=iPad based, 4=no preference, 7=paper based), subjects reported a mean score of 3.36 (SD 1.55), demonstrating a slight but not statistically significant preference for iPad. Technicians uniformly found the iPad app easier to administer and less time-consuming for them. Conclusions: Given the growing population of individuals with vascular cognitive impairment, it is crucial to test whether this accessible, cost-effective, mobile testing modality can be effectively utilized to assess change in cognitive function after stroke. Our preliminary results indicate that iPad based interventions area promising means to meet this goal.

There are studies showing that gene polymorphisms within the transforming growth factor-β (TGF-β) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-β level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale – Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-β levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-β level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-β level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-β signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.

Background: Cardiometabolic disorders are a major contributor to cognitive decline and Alzheimer’s disease and related dementias; yet, gaps remain in our understanding of glucose homeostasis and cognitive function. Continuous glucose monitoring (CGM) offers new opportunities to understand these relationships beyond what is possible from fasting glucose and HbA1c. Hypothesis: CGM abnormalities will be associated with worse cognitive function. Methods: CGM was measured in Multi-Ethnic Study of Atherosclerosis (MESA) participants concurrently with cognitive testing in 2022-2024. We report unadjusted and adjusted standardized estimates from linear regression of CGM metrics as quartiles (including mean, variability measures, and time in range variables) with global cognitive function (Composite = mean of z-scores for Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC, attention/processing speed), Digit Span (DS, forwards and backwards recall of working memory)) and cognitive domain scores (from the Uniform Data Set (UDS) neuropsychological battery version 3: memory immediate and delayed, attention/processing speed, executive function, visuospatial, language). Results: A total of 892 participants without diabetes (mean age of 76 years; 57% female; 47% white; 24% African American; 19% Hispanic; 10% Asian) were included. Fasting glucose, HbA1c, and CGM variables were significantly associated with unadjusted global cognitive function and processing speed ( Figure 1A ); yet, substantial attenuation was seen with adjustment. Results for memory delayed domain were similar to those for global cognitive composite score except for clinical measurements, with similar but weaker results for memory immediate recall domain (data not shown). In contrast, estimates for coefficient of variation, mean amplitude of glycemic excursions, Time Below Range, Time Above Range, and Time In Tight Range with attention/processing speed domain were significant in both unadjusted and adjusted models ( Figure 1B ). Results for other domains were weaker and not significant (data not shown). Conclusion: This first cross-sectional look from MESA suggests a high level of heterogeneity in the associations between different CGM metrics and indicators of cognitive function; however, the stronger estimates for attention/processing speed, often the earliest indicator of cognitive decline, suggest that CGM metrics may offer insight into the pathways from dysglycemia to cognitive risk.

Insomnia is a condition affecting 10% to 15% of the adult population and is characterized by difficulty falling asleep, difficulty staying asleep, or nonrestorative sleep, accompanied by daytime impairment or distress. This study evaluates APD125, a selective inverse agonist of the 5-HT(2A) receptor, for treatment of chronic insomnia, with particular emphasis on sleep maintenance. In phase 1 studies, APD125 improved sleep maintenance and was well tolerated. Adult subjects (n=173) with DSM-IV defined primary insomnia were randomized into a multicenter, double-blind, placebo-controlled, 3-way crossover study to compare 2 doses of APD125 (10 mg and 40 mg) with placebo. Each treatment period was 7 days with a 7- to 9-day washout period between treatments. Polysomnographic recordings were performed at the initial 2 screening nights and at nights (N) 1/2 and N 6/7 of each treatment period. APD125 was associated with significant improvements in key sleep maintenance parameters measured by PSG. Wake time after sleep onset decreased (SEM) by 52.5 (3.2) min (10 mg) and 53.5 (3.5) min (40 mg) from baseline to N 1/2 vs. 37.8 (3.4) min for placebo, (P < 0.0001 for both doses vs. placebo), and by 51.7 (3.4) min (P = 0.01) and 48.0 (3.6) min (P = 0.2) at N 6/7 vs. 44.0 (3.8) min for placebo. Significant APD125 effects on wake time during sleep were also seen (P < 0.0001 N 1/2, P < 0.001 N 6/7). The number of arousals and number of awakenings decreased significantly with APD125 treatment compared to placebo. Slow wave sleep showed a statistically significant dose-dependent increase. There was no significant decrease in latency to persistent sleep. No serious adverse events were reported, and no meaningful differences in adverse event profiles were observed between either dose of APD125 and placebo. APD125 was not associated with next-day psychomotor impairment as measured by Digit Span, Digit Symbol Copy, and Digit Symbol Coding Tests. APD125 produced statistically significant improvements in objective parameters of sleep maintenance and sleep consolidation and was well tolerated in adults with primary chronic insomnia.