Measures Of Processing Speed Research Articles

Application of cognitive remediation in the world: new experiences from two schizophrenia rehabilitation centers in Togo and Benin

PurposePeople with schizophrenia in Sub-Saharan Africa often live in very difficult conditions, suffer important social isolation and usually do not receive any kind of treatment. In this context, some non-governmental initiatives have come to light, providing accommodation, food, primary healthcare, medications and, in some cases, education and rehabilitation. The aims of this study were to assess feasibility, effects, and acceptability of a Cognitive Remediation Therapy (CRT) intervention in the particular context of psychiatric rehabilitation in Togo and Benin.MethodsPatients diagnosed with schizophrenia accessing the “Saint Camille” association rehabilitation centers in Togo and Benin during the enrollment period were allocated consecutively with a 1:1 proportion to receive a manualized CRT intervention (46 one-hour sessions over 14 weeks) or continuing Treatment As Usual (TAU). The assessment included validated measures of cognitive performance and real-world functioning and was performed at baseline and at the conclusion of treatment.ResultsAll subjects that were invited into the study agreed to participate and completed the intervention, for a total of 36 participants. CRT produced greater improvements than TAU in processing speed, working memory, verbal memory, cognitive flexibility, and executive functions measures, with moderate to large effect sizes, in particular in processing speed and working memory domains.ConclusionsCRT represents a feasible and effective psychosocial intervention that can be implemented even in contexts with very limited resources, and could represent an important instrument to promote the rehabilitation process of people living with schizophrenia in low-income countries.

Speed of processing training to improve cognition in moderate to severe TBI: a randomized clinical trial.

Moderate to severe traumatic brain injury (TBI) often results in cognitive deficits. Processing speed (PS) deficits are common, exerting a significant impact on daily life. Few studies have examined the efficacy of cognitive rehabilitation specifically for PS deficits in moderate to severe TBI. Examine the efficacy of Speed of Processing Training (SOPT) in moderate to severe TBI. This protocol is a 10-session behavioral intervention for PS deficits that has been successfully used with other cognitively impaired populations. This double-blind, placebo-controlled, randomized clinical trial included 46 participants with moderate to severe TBI, 22 randomly assigned to the treatment group and 24 to the placebo-control group. Baseline and follow-up measures included a task similar to the training task (UFOV), measures of near transfer (neuropsychological measures of processing speed: Symbol Digit Modalities Test (SDMT), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Symbol Search, WAIS-IV Coding) and measures of far transfer [neuropsychological measures of learning and memory: the California Verbal Learning Test-II (CVLT-II), Memory Assessment Scales - Prose Memory (MAS-PM)]. Significant improvement from pre-to post-SOPT was observed on all subtests of the UFOV, which is similar to the training task. There was no significant difference on neuropsychological measures of PS or new learning and memory post-treatment. Neuropsychological assessment 6-months post-treatment showed no significant change in PS ability over time. Monthly booster sessions did not impact performance at the 6-month follow-up. Consistent with the SOPT literature, SOPT improves PS ability as measured by the UFOV, a task similar to the training task, in moderate to severe TBI. However, neither near nor far transfer was noted. That is, no improvement was noted on neuropsychological measures of PS.

Executive Functions, Processing Speed, and Memory Performance: Untangling the Age-related Effects

Abstract Context: Age-related decline in memory function is a universal phenomenon. However, several factors are known to affect memory decline associated with aging. Aim: The present research aimed to study the differences between young adults and older adults in neurocognitive functions. It also aimed to examine the relative contribution of aging and executive functions to memory performance. Subjects and Methods: The sample consisted of two groups: 43 young adults and 40 older adults. Participants were selected from the community using purposive sampling. Each participant underwent screening using the Edinburgh Handedness Inventory, Modified Mini Screen, and Global Cognitive Screen. A detailed neuropsychological assessment was individually conducted using standardized measures of executive functions, processing speed, episodic memory, and semantic memory. We examined group differences between younger and older participants using the Mann Whitney U test. Additionally, we investigated the contributions of age, processing speed, and executive function to memory through stepwise multiple regression analysis. Results: Analysis of the results suggests significantly worse performance by older participants compared to younger participants on learning and memory (p<.001), semantic memory (p<.001), processing speed (p<.001), and executive functions (p<.001). Our results further indicate that age, processing speed, and executive functions were associated with better performance in learning and memory. However, age emerged as the strongest predictor, followed by processing speed and working memory. Conclusion: Our study demonstrates that aging plays the most significant role in predicting the decline of learning and memory, as well as semantic memory. However, executive functions and processing speed can differentially influence age-associated memory decline. Future studies are warranted on larger populations and more diverse age groups to better comprehend the differential roles of speed, executive functions, and aging on memory performance. We recommend developing age- and education-based normative data for neuropsychological tools specifically tailored to the Indian population.

Comparison of performance on the oral versus written trail making test in patients with movement disorders

The Oral Trail Making Test (O-TMT) was designed as a clinical analog of the written version (W-TMT). There is debate, however, about whether the measurement of processing speed and set shifting is equivalent between versions. Given the administration advantages of the O-TMT – especially for patients with motor impairments – we examined convergent validity with the W-TMT in patients with movement disorders. Fifty patients (n = 43 idiopathic Parkinson’s disease [PD]) were evaluated in a movement disorders clinic. Patients averaged 71 years old (SD = 8.07 years), 16 years of education (SD = 2.30 years), and the majority were non-Hispanic White (n = 46) and male (n = 35). In addition to other neuropsychological measures, patients completed the O-TMT and the W-TMT, counterbalanced and separated by thirty-minutes. Part A scores on O-TMT and W-TMT were not significantly correlated. In contrast, Part B scores were strongly correlated, such that slower performances on O-TMT Part B corresponded with slower performances on W-TMT Part B. Discrepancy scores (Part B minus Part A completion times) were also strongly correlated, such that more time on O-TMT, indicative of slower set shifting speed, corresponded with more time on W-TMT. Better performances on both O-TMT B and W-TMT B were associated with better scores on measures of overall cognitive status, verbal learning, and both phonemic and semantic fluency. Part B of the O-TMT shows promise as an analog for Part B of the W-TMT when evaluating set shifting abilities in patients with movement disorders. Future research with diverse patient populations is recommended to establish generalizability.

Apathy, cognition and beta amyloid in African Americans in the AA‐FAIM cohort

AbstractBackgroundThe prodrome of cognitive declines and/or dementia may include late‐life neuropsychiatric symptoms such as apathy. In primarily non‐Hispanic White samples, apathy associates with both cognition and amyloid deposition in cognitively intact patients and those with Alzheimer’s disease (AD). However, little is known about these relationships in African Americans, who are both disproportionately affected by AD and under‐represented in AD research. Apathy could reflect higher levels of proteinopathy or occur co‐morbidly, exacerbating its deleterious effects. We examined associations between apathy and cognition and their potential moderation by plasma beta amyloid in cognitively healthy African American participants.MethodStudy participants enrolled in African Americans Fighting Alzheimer’s In Mid‐Life(AA‐FAIM, a linked study to the WRAP and Wisconsin ADRC) were included in the analytic sample (N = 166; Table 1) if they had ≥1 cognitive visits, plasma amyloid biomarker data, and apathy ratings by study partners using the Neuropsychiatric Inventory Questionnaire (NPI‐Q) or the Apathy Evaluation Scale (AES). Cognitive outcomes included performance on measures of processing speed, mental flexibility and immediate and delayed memory. We used linear mixed models to examine association of baseline apathy with cognitive performance measures at multiple time points, and the moderation of apathy‐cognition relationships by plasma Aβ42/40 ratio (C2N, USA). Apathy‐cognitive outcome pairings were selected based on significant findings from a proof‐of‐concept linear mixed effects analysis of the full Wisconsin ADRC sample.ResultResults are shown in Table 2. Among AA‐FAIM participants, NPI‐Q apathy was associated with RAVLT immediate (estimate = ‐7.7, p = .001) and delayed recall (estimate = ‐3.2, p = .001). However, AES was unrelated to Trails A or B performance. There were no associations between plasma amyloid or the Aβ42/40*apathy interaction term with any cognitive outcomes.ConclusionPartner‐rated apathy, but not plasma Aβ42/40, was related to cognition in our African American participants, an important finding given limited data available on this population. It will be critical to address apathy and its antecedents to improve the cognitive and affective health of African American older adults. Future research needs to expand cohorts to African American and other diverse populations to investigate disease mechanisms in Alzheimer’s disease and related dementias more inclusively.

The Mobile Toolbox for assessing cognition in older adults: associations with standardized cognitive testing and amyloid and tau PET

AbstractBackgroundRemote, smartphone‐based cognitive assessments such as the Mobile Toolbox (MTB) can improve our ability to detect subtle, yet meaningful cognitive changes that are affected early on by Alzheimer’s disease (AD) pathology. The goal of our study was to investigate which MTB tests are sensitive to subtle cognitive deficits due to early amyloid and tau deposition.MethodThe MTB will be administered to N = 100 clinically normal (CN) older adults who have retrospective and prospective clinical, cognitive and AD biomarker data from three well‐characterized prospective cohort‐studies of CN older adults: the Harvard Aging Brain Study and the affiliated Subjective Cognitive Decline and Instrumental Activities of Daily Living cohorts. The MTB includes six measures of fluid cognition, including episodic memory (Picture Sequence Memory and Face‐Name Associations), executive functions (Dimensional Change Card Sort, Flanker), working memory (Memory for Sequence), processing speed (Number‐Symbol Match), and two measures of crystallized cognition (Spelling and Vocabulary). Using confirmatory factor analysis, MTB baseline data will be used to determine which MTB tests are most strongly associated with established clinical assessments (i.e., measures included in the Preclinical Alzheimer’s Cognitive Composite‐5 [PACC5]) as well as amyloid and tau biomarkers on positron emission tomography (PET) imaging.ResultPreliminary MTB data was available on 15 participants (age 74.3±8.2, 63% female, 16.6±2.9 years of education, MMSE 29±1.5). Table 1 shows exploratory correlation analyses, revealing that both MTB crystallized measures were associated with education but not age or sex. As expected, worse performance on MTB memory measures were associated with lower PACC5 scores, and greater amyloid and tau burden, albeit at trend‐level. Executive function and processing speed measures were not related to amyloid but did show associations with entorhinal tau.ConclusionWhile preliminary, these findings suggest that the MTB may help elucidate the subtle cognitive deficits that are associated with early AD pathology. In addition to memory measures, the MTB fluid measures capture various aspects of cognitive function that are also relevant to preclinical AD. Data collection is ongoing, and next steps include examining which (combination of) MTB measures are most sensitive for detecting emerging AD pathology and to track cognitive change over time.

Gestational Hypertension and Midlife Cognition: The CARDIA Study

AbstractBackgroundGestational hypertension (GH) increases the risk of cardiovascular diseases, which may contribute to worse cognitive outcomes, and yet little is known about the long‐term impact of GH on cognition. We investigated the association of GH with midlife cognitive performance and decline in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.MethodsWe studied 1,273 parous Black and White women (106 with GH and 1167 without GH) aged 18‐30 years at baseline (1985‐86) who were followed up to Year 30 (mean age 55.2±3.6 years) when five cognitive tests measuring global cognition, memory, processing speed, executive function, and verbal fluency were administered. Accelerated decline over five years was defined as a decline ≥1.5 standard deviations from the mean change on each of the three tests available at year 25, measuring processing speed, memory, and executive function. GH, defined as having new onset hypertension in pregnancy without proteinuria, was self‐reported for each pregnancy since the previous visit up to 30 years. We conducted linear and logistic regression to assess the association of GH with cognitive performance and decline.ResultsCompared with women who did not develop GH during pregnancy, those with GH were more likely to be Black (62% vs 50%) and have obesity (22% vs 11%), and lower diet quality (CARDIA A Priori Diet Quality Scores) at baseline. After adjusting for age, race, education, number of pregnancies, and baseline cardiovascular and behavior risk factors (diabetes, obesity, smoking, alcohol use, physical activity, and diet quality), having GH was significantly associated with lower cognitive performance (z‐standardized) at year 30 in global cognition (‐0.27, 95% CI ‐0.44 to ‐0.11), processing speed (‐0.25, 95% CI ‐0.44 to ‐0.07), and verbal fluency (‐0.20, 95% CI ‐0.38 to ‐0.02). Additional adjustment for hypertension, diabetes, and obesity up to Year 30 did not change the results. GH was also associated with higher odds of experiencing an accelerated decline in processing speed over 5 years (9.2% vs. 4.5%, odds ratio 2.48, 95% CI 1.07 to 5.74), after adjustment for all covariates.ConclusionGH is independently associated with worse cognitive performance and accelerated decline in midlife.

Fatigue Interacts with Amyloid Status To Predict Daily Working Memory Performance in Preclinical Alzheimer’s Disease

AbstractBackgroundSmartphone‐based cognitive assessment has the potential to reduce barriers to cognitive screening and increase sensitivity to detect preclinical Alzheimer’s disease (AD). Ecological momentary assessment of cognition is novel, and it is not yet well understood how psychological factors (i.e., mood, stress, and fatigue) may impact cognitive performance in remote, real‐world settings. We aimed to evaluate whether psychological factors influence daily cognitive performance differently between older adults with and without AD‐related pathologic change.MethodParticipants (N = 73) were cognitively unimpaired adults aged 60‐80 years (71% female, 89% White, 16.5 mean years of education) recruited for a digital cognitive assessment study. Participants had amyloid (Aβ) PET imaging results available from prior research participation [(n = 25 Aβ positive (Aβ+) and n = 48 Aβ negative (Aβ‐)]. A modified Telephone Interview for Cognitive Status (TICSm) score of ≥34 was used to indicate normal cognition. Participants completed 8 consecutive days of cognitive assessment using Mobile Monitoring of Cognitive Change (M2C2), a smartphone‐based testing platform developed as part of the National Institute of Aging’s Mobile Toolbox. Brief (i.e., 3‐4 minute) M2C2 sessions were assigned three times daily (morning, afternoon, and evening). Tasks included measures of visual working memory (WM, “Color shapes”), processing speed (PS, “Symbol search”), and episodic memory (EM, “Prices”). Multilevel modeling was used to examine the impact of self‐reported mood, stress, fatigue, and Aβ status on daily cognitive performance while controlling for age, sex, education, and time of day.ResultDaily fatigue was found to interact with amyloid status such that Aβ+ individuals performed worse on the WM task when experiencing higher levels of fatigue (Est. = .004, p = .01) Higher levels of daily stress were associated with poorer performance on the PS task (Est. = ‐.0005, p = .03) but no interaction with Aβ status was observed. There were no significant relationships between mood and cognitive performance.ConclusionWe demonstrated that psychological factors including fatigue and stress may impact performance on remote cognitive assessments. Results also suggested that fatigue may impact daily cognitive performance more among those with AD pathological change. These preliminary results suggest that psychological factors should be considered when determining optimal windows for remote cognitive screening.

Comparing Clinical Diagnosis of Domains of Impairment in individuals with Mild Cognitive Impairment with the NIH Toolbox‐Cognitive Battery Performance

AbstractBackgroundMild Cognitive Impairment (MCI) represents the phase between age‐associated cognitive decline and Alzheimer’s disease and related dementias. Examination of these individuals may be especially important through computer‐based batteries such as the NIH Toolbox‐Cognition Battery (NIHTB‐CB). To inform NIHTB‐CB validity, we compared MCI patients’ performance against categories of cognitive impairment defined by the consensus‐based clinical diagnosis form of the National Alzheimer’s Disease Coordinating Center (NACC) Unified Data Set UDS3. We expected a correspondence between MCI consensus‐based clinical deficit areas and specific NIHTB‐CB task performance.MethodRetrospective data analysis was conducted on 65 MCI participants from the Michigan Alzheimer’s Disease Research Center, with a mean age of 74±8.3, 65% female, who completed UDS3 and NIHTB‐CB measures. The UDS3 forms consist of interviews, medical/neurological examinations, and neuropsychological testing, with a clinical consensus‐based diagnosis form listing domains of cognitive impairment representing memory, language, attention, executive, and visuospatial functioning. Four domain impairment groupings with a minimum of 10 participants each were established (Executive Functioning, n = 10; Memory, n = 27; Memory+Executive Functioning, n = 17; and Memory+Language n = 11) and compared to NIHTH‐CB performance. ANOVAs adjusted for demographics and post hoc tests were conducted to differentiate across clinical consensus categories for the MCI participants.ResultTwo NIHTB‐CB measures yielded significant differences across the clinical grouping: Picture Sequence Memory (PSM, F = 3.3, p = 0.03) and Pattern Comparison (PC, F = 4.1, p = 0.01). For PSM, post hoc tests demonstrated higher scores for the Executive compared to Memory+Executive (PSM: p<0.02) groups with a trend for Executive versus Memory groups (p<.07). For PC, the Memory group performed better than both the Memory+Executive (p<.02) and Memory+Language (p<.04).ConclusionThe better memory performance on PSM of the MCI Executive group compared to the two groups with memory impairment is consistent with expectation. PC, as a measure of executive ability and processing speed was sensitive to clinically diagnosed executive impairment. Lower scores for the Memory+Language group on PC were unexpected. Efficient language functioning may be necessary for complex pattern comparison as dimensions shift. Findings support the validity of NIHTB‐CB. They also suggest the need for additional research on language demands for executive measures.

Cerebrovascular reactivity in amnestic and non‐amnestic mild cognitive impairment

AbstractBackgroundCerebrovascular disease (CVD) is implicated in the pathogenesis and clinical presentation of Alzheimer’s Disease. Cerebrovascular reactivity (CVR) is considered a more direct estimate of cerebrovascular integrity. CVR is a potential promising biomarker for examining pathological cognitive decline in older adults though, to date, findings have been inconclusive, possibly partly due to variability in methodological approaches. In this study, we add to the limited literature on CVR in mild cognitive impairment (MCI). We provide preliminary evidence for CVR differences in MCI phenotypes compared to older adult cognitively normal controls. We hypothesized that they amnestic phenotype (aMCI) will have lower CVR than non‐amnestic (naMCI) and both groups will show lower CVR compared to controls. We also performed exploratory correlational analyses between CVR and neuropsychological test scores.MethodCVR was assessed in 22 controls, 11 aMCI, 9 naMCI cohorts using a breath‐holding task functional magnetic resonance imaging (fMRI). fMRI data were preprocessed and analyzed using AFNI. All participants underwent neuropsychological testing. T‐tests and ANOVA/ANCOVA analyses were conducted to compare controls to MCI groups on CVR metrics and cognitive tests of memory, language, processing speed, and executive functioning. Partial correlation analyses between CVR derived from regions‐of‐interest (Yeo 1‐7 ROIs) and different cognitive functions were conducted.ResultsCVR was found to be significantly lower in MCI compared to controls across all Yeo functional networks, ps < .001, which was mostly driven by the aMCI phenotype. naMCI showed intermediate patterns between aMCI and controls, though results were not significant, ps > .05. Regional CVR values along Yeo networks were positively correlated with cognitive measures of processing speed, executive functioning, and memory.ConclusionThis is the first study to evaluate CVR differences in MCI phenotypes. Consistent with previous research, we found that CVR is lower in MCI compared to controls. While group differences between naMCI and controls (also between naMCI and aMCI) did not reach statistical significance, visual inspection of CVR mean values showed preliminary evidence that naMCI had lower mean values across all ROIs compared to controls and higher mean values compared to aMCI. Future research is needed to examine differences in CVR between MCI phenotypes.

Cross‐cultural properties of the Cross‐cultural Dementia Screening test and the European Cross‐Cultural Neuropsychological Test Battery

AbstractBackgroundCross‐cultural neuropsychological tests are essential to avoid potential cultural biases during the performance and score interpretation in diverse populations. We aimed to compare the performance of healthy controls in the Cross‐cultural Dementia Screening test and the European Cross‐Cultural Neuropsychological Test Battery in the majority and minority populations living in Spain.MethodThree hundred cognitively healthy participants were enrolled (58% women, age range 18‐90). One hundred from majority population (Spaniards), one hundred from minority population from Colombia, and one hundred from different minority populations, including participants from Latin America (66%, excluding participants from Colombia), Spaniards of Romani (gipsy) ethnicity (14%), Arab League (10%), and East Europe (10%). We matched the three groups controlling for sex, age, and level of education. All scores on CCD and CNTB were compared and correlated with an acculturation scale, controlling for age and years of education.ResultThere were no differences between groups in most of the items. Only processing speed measures of the CCD (Sun‐Moon test) and verbal fluency tasks of the CNBT showed statistically significant differences between groups. Scores on the acculturation scale were not associated with the neuropsychological test performance of all participants.ConclusionThe absence of differences between groups or acculturation influence on the scores supports the favourable cross‐cultural properties of the CCD and the CNTB. However, some tasks could still be more influenced, especially those associated with processing speed and verbal fluency, which suggests the need to further study and develop new tests and paradigms with better cross‐cultural properties.

Late positive potential component and cognitive functioning in occipital area of Mild Cognitive Impairment

AbstractBackgroundMild Cognitive Impairment (MCI) is a prodromal stage of Alzheimer’s disease and other dementias (Langa & Levine, 2014). It has been suggested that a late event‐related potential (ERP) called the late positive potential (LPP) is related to cognitive functioning including sustained attention and reaction time in people with MCI (Waninger et al., 2018). The LPP in the occipital area was also suggested to be a biomarker of MCI (Liu et al., 2022). However, it remains unclear whether LPP in the occipital area is related to cognitive functioning.MethodWe collected EEG of 50 people with MCI (mean age 72.44±7.96; education: 5.52±1.07) by using a 20‐channel EEG recording system while participants performed the simple vigilance task (SVT). Their reaction time (ms) was taken as a measure of sustained attention. Vienna Reaction Time Task (VRTT) (Schuhfried GmbH, Moedling, Austria) was used to measure processing speed and inhibition while separating motor action (measured as a motor time) and cognitive processing (measured as a reaction time). Mini‐Mental State Examination (MMSE) was used to measure the severity of cognitive impairment (mean score: 26.20±2.44). Correlation analysis was used to analyze the liner relationship between the average LPP amplitude in the occipital areas (Oz, O1, and O2; time window: 400 to 800 ms after stimulus presentation), reaction time on the three versions of the VRTT, and reaction time on the SVT.ResultWe found significant correlations between reaction time on the SVT and motor time on VRTT (S1: p = 0.015; S2: p = 0.075; S3: p = 0.021;), but we found no significant correlations between reaction time on the SVT and VRTT (ps > 0.193), no significant correlations between LPP amplitude in the occipital areas and reaction time on any of the tasks (SVT: p > 0.056, VRTT: ps > 0.288) or between LPP amplitude and motor time on any version of the VRTT (ps > 0.500).ConclusionOur preliminary results indicate that LPP amplitude measured over the occipital area was not significantly associated with sustained attention or inhibition.

The Influence of Prior Head Injury on Late‐Life Cognition and White Matter Microstructure in Older Adults At‐Risk of Alzheimer’s disease

AbstractBackgroundThe long‐term combined effects of mild traumatic brain injury (mTBI) and APOE ε4‐allele carrier status (APOE+/‐), a genetic risk factor of Alzheimer’s disease (AD), on cognition and white matter structural integrity in older adults at‐risk of AD is not fully understood.MethodTo investigate mTBI effects on late‐life neurobehavioural outcomes, a subsample of the PREVENT‐AD cohort was analyzed. Participants were cognitively normal adults over age 55 with a parental or multiple‐sibling history of AD. The mTBI group included individuals who self‐reported at least one prior mTBI with loss of consciousness and/or memory gap (n = 48, 33.3% APOE4+). Rey Auditory Verbal Learning Test measured immediate and delayed memory, Color‐Word Interference Test measured cognitive flexibility and inhibitory control, and Trail Making Test measured processing speed and attention.The control group included demographically‐matched (age, sex, years of education) participants from the same cohort without self‐reported mTBI (n = 62, 29.0% APOE4+). Data were analyzed using 2‐way ANOVAs with weighted means on years of education, corrected for multiple comparisons. To evaluate underlying structural differences in white matter tracts between mTBI and control groups, diffusion tensor imaging (DTI) metrics, including fractional anisotropy, axial and radial diffusivity, using the JHU‐atlas parcellation.ResultsmTBI/APOE4+ individuals performed significantly worse on cognitive outcomes of delayed recall, cognitive flexibility, and inhibitory control compared to controls; however, they performed significantly better on tests of processing speed and visual attention compared to mTBI/APOE4‐ individuals. DTI results showed that the mTBI group, compared to the control group, had significantly decreased axial diffusivity in the left internal capsule, right superior longitudinal fasciculus, and superior frontooccipital fasciculus (SFOF) (p<0.05 uncorrected). Within the mTBI group, significant positive correlation between lower processing speed and decreased axial diffusivity of SFOF, accounting for age and sex.ConclusionOur findings suggest that prior mTBI impacts cognitive aging in older adults at‐risk of AD differentially depend on APOE4 status, where APOE4+ individuals with prior mTBI had worse working memory, cognitive flexibility, and inhibitory control but better processing speed outcomes. Lower cognitive outcomes in mTBI individuals may be supported by decreased diffusivity in specific white matter tracts. These results can inform dementia prevention in these individuals.

The Influence of Prior Head Injury on Late‐Life Cognition and White Matter Microstructure in Older Adults At‐Risk of Alzheimer’s disease

AbstractBackgroundThe long‐term combined effects of mild traumatic brain injury (mTBI) and APOE e4‐allele carrier status (APOE+/‐), a genetic risk factor of Alzheimer’s disease (AD), on cognition and white matter structural integrity in older adults at‐risk of AD is not fully understood.MethodTo investigate mTBI effects on late‐life neurobehavioural outcomes, a subsample of the PREVENT‐AD cohort was analyzed. Participants were cognitively normal adults over age 55 with a parental or multiple‐sibling history of AD. The mTBI group included individuals who self‐reported at least one prior mTBI with loss of consciousness and/or memory gap (n = 48, 33.3% APOE4+). Rey Auditory Verbal Learning Test measured immediate and delayed memory, Color‐Word Interference Test measured cognitive flexibility and inhibitory control, and Trail Making Test measured processing speed and attention. The control group included demographically‐matched (age, sex, years of education) participants from the same cohort without self‐reported mTBI (n = 62, 29.0% APOE4+). Data were analyzed using 2‐way ANOVAs with weighted means on years of education, corrected for multiple comparisons. To evaluate underlying structural differences in white matter tracts between mTBI and control groups, diffusion tensor imaging (DTI) metrics, including fractional anisotropy, axial and radial diffusivity, using the JHU‐atlas parcellation.ResultmTBI/APOE4+ individuals performed significantly worse on cognitive outcomes of delayed recall, cognitive flexibility, and inhibitory control compared to controls; however, they performed significantly better on tests of processing speed and visual attention compared to mTBI/APOE4‐ individuals. DTI results showed that the mTBI group, compared to the control group, had significantly decreased axial diffusivity in the left internal capsule, right superior longitudinal fasciculus, and superior frontooccipital fasciculus (SFOF) (p<0.05 uncorrected). Within the mTBI group, significant positive correlation between lower processing speed and decreased axial diffusivity of SFOF, accounting for age and sex.ConclusionOur findings suggest that prior mTBI impacts cognitive aging in older adults at‐risk of AD differentially depend on APOE4 status, where APOE4+ individuals with prior mTBI had worse working memory, cognitive flexibility, and inhibitory control but better processing speed outcomes. Lower cognitive outcomes in mTBI individuals may be supported by decreased diffusivity in specific white matter tracts. These results can inform dementia prevention in these individuals.

Higher order neurocognition in pediatric brain tumor survivors: What can we learn from white matter microstructure?

Pediatric brain tumor survivors (PBTS) experience neurocognitive late effects, including problems with working memory, processing speed, and other higher order skills. These skill domains are subserved by various white matter (WM) pathways, but not much is known about these brain-behavior links in PBTS. This study examined the anterior corona radiata (ACR), inferior fronto-occipital fasciculi (IFOF), and superior longitudinal fasciculi (SLF) by analyzing associations among diffusion metrics and neurocognition. Thirteen PBTS and 10 healthy controls (HC), aged 9-14years, completed performance-based measures of processing speed and executive function, and parents rated their child's day-to-day executive skills. Children underwent magnetic resonance imaging (MRI) with diffusion weighted imaging that yielded fractional anisotropy (FA) and mean diffusivity (MD) values. Independent samples t-tests assessed group differences on neurocognitive and imaging measures, and pooled within-group correlations examined relationships among measures across groups. PBTS performed more poorly than HC on measures of processing speed, divided attention, and shifting (d=-1.08 to -1.44). WM microstructure differences were significant in MD values for the bilateral SLF and ACR, with PBTS showing higher diffusivity (d=0.75 to 1.21). Better processing speed, divided attention, and shifting were associated with lower diffusivity in the IFOF, SLF, and ACR, but were not strongly correlated with FA. PBTS demonstrate poorer neurocognitive functioning that is linked to differences in WM microstructure, as evidenced by higher diffusivity in the ACR, SLF, and IFOF. These findings support the use of MD in understanding alterations in WM microstructure in PTBS and shed light on potential functions of these pathways.

Cerebellar Neuromodulation Impacts Reading Fluency in Young Adults.

The cerebellum is traditionally associated with the control of coordinated movement, but ample evidence suggests that the cerebellum also supports cognitive processing. Consistent with this, right-lateralized posterolateral cerebellar regions are engaged during a range of reading and reading-related tasks, but the specific role of the cerebellum during reading tasks is not clear. Based on the cerebellar contribution to automatizing movement, it has been hypothesized that the cerebellum is specifically involved in rapid, fluent reading. We aimed to determine whether the right posterolateral cerebellum is a specific modulator of reading fluency or whether cerebellar modulation is broader, also impacting reading accuracy, rapid automatized naming, and general processing speed. To do this, we examined the effect of transcranial direct current stimulation (tDCS) targeting the right posterolateral cerebellum (lobules VI/VII) on single-word reading fluency, reading accuracy, rapid automatized naming, and processing speed. Young adults with typical reading development (n = 25; 15 female sex assigned at birth, 10 male sex assigned at birth, aged 18-28 years [M = 19.92 ± 2.04 years]) completed the reading and cognitive measures after 20 min of 2 mA anodal (excitatory), cathodal (inhibitory), or sham tDCS in a within-subjects design. Linear mixed effects models indicated that cathodal tDCS decreased single-word reading fluency scores (d = -0.36, p < 0.05) but did not significantly affect single-word reading accuracy, rapid automatized naming, or general processing speed measures. Our results suggest that the right posterolateral cerebellum is involved in reading fluency, consistent with a broader role of the cerebellum in fast, fluent cognition.

12 Differential Processing Efficiency Skills in Survivors of Pediatric Primary CNS Cancer and Cancers of non-CNS Origin

Objective:Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.Participants and Methods:Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores &gt;1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.Results:The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p &lt; 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p &lt; 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p &lt; 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p &lt; 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p&lt;.001) and semantic fluency (ß=7.59, p=.007).Conclusions:These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

51 Impact of Blast Exposures on the Cognitive Abilities of Warfighters

Objective:There is growing evidence to indicate that blast exposure military personnel experience throughout their career can have a negative impact on their brain health. The majority of research in the area of blast related neurotrauma has been focused on traumatic brain injury (TBI); however, the blast exposure may often be independent of TBI. It is common in both active duty military and veterans to report years of blast exposure from combat and training. The objective of this study was to explore the relationship between blast exposure and cognitive functioning in military personnel seeking treatment for a mild TBI.Participants and Methods:Participants were recruited from a military hospital while enrolled in a multidisciplinary treatment program for TBI. All patients had at least one diagnosed mTBI as well as persistent cognitive complaints. Exclusion criteria included invalid performance on a performance validity test and a symptom validity test. 97 participants were included in the analysis with an average age of 34.0 (SD = 7.9) and average 4.0 combat deployments (SD = 3.6). Blast exposure history was measured by the overall score from the Blast Exposure Threshold Survey (BETS) which assessed the frequency and duration of use of various blast sources. Outcomes included the Neurobehavioral Symptom Inventory (NSI) and the Global Deficit Scale (GDS) an objective measure of cognitive deficiency. GDS was calculated from seven measures: Hopkins Verbal Learning Test-Revised Total and Delayed Recall (HVLT-TR and HVLT-DR); DKEFS System Color-Word Condition 3 Inhibition (CW3), Color-Word Condition 4 Switching (CW4) and Trail Making Condition 3 Letter Sequencing (TM3), Paced Auditory Serial Addition Test (PASAT), and the Symbol Digit Modality Test (SDMT). Demographically corrected t-scores (M=50, SD = 10) were converted to deficit scores and averaged to calculate GDS. To adjust for nonnormal distributions, non-parametric statistics were examined.Results:The BETS was not related to GDS (rho = -.055); however, there was a significant correlation between higher levels on the BETS and better performance on measures of selective attention (PASAT rho = .307) and processing speed (SDMT rho = .218). The correlation between BETS and the other neuropsychological measures were not meaningful (all rho’s &lt;.10). Those with an impaired GDS, did not differ from others on the BETS. BETS was also not associated with neurobehavioral symptoms (rho = .125). BETS had moderate correlations with number of combat deployments (rho =.483), severity of combat exposure (rho =.556). It was not related to education (rho = .004) or pre-morbid intelligence (rho =-.029).Conclusions:The BETS was not related to GDS (rho = -.055); however, there was a significant correlation between higher levels on the BETS and better performance on measures of selective attention (PASAT rho = .307) and processing speed (SDMT rho = .218). The correlation between BETS and the other neuropsychological measures were not meaningful (all rho’s &lt;.10). Those with an impaired GDS, did not differ from others on the BETS. BETS was also not associated with neurobehavioral symptoms (rho = .125). BETS had moderate correlations with number of combat deployments (rho =.483), severity of combat exposure (rho =.556). It was not related to education (rho = .004) or pre-morbid intelligence (rho =-.029).

42 Associations Between Mild Traumatic Brain Injury, Executive Function, and Criminal Justice Involvement among Veterans and Service Members: a LIMBIC-CENC study

Objective:To examine relationships between history of mild traumatic brain injury (mTBI), neuropsychological measures of executive function, and lifetime history of criminal justice (CJ) involvement among combat-exposed Veterans and Service Members (V/SM).Participants and Methods:Participants were combat-exposed V/SM who completed a baseline assessment for the multicenter Long-term Impact of Military-Relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium study (N=1,341) and had adequate engagement/symptom reporting on measures of performance and symptom validity (i.e., Medical Symptom Validity Test and Mild Brain Injury Atypical Symptoms Scale). Neuropsychological battery included the Trail Making Test (A and B), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span subtest, and the National Institute of Health (NIH) Toolbox Flanker subtest. Lifetime history of brain injury, criminal justice involvement, and demographics were collected. Participants were 87% male, 72% white, with a mean age of 40 years (SD=9.67). Eighty-one percent had at least some college education. Nineteen percent were active duty. Eighty percent of Veterans and 86% of Service Members reported a history of &gt;1 mTBI, and of these 31% and 47% respectively experienced 3+ mTBIs.Results:Three groups were composed based on level of involvement with the CJ system: 1.) No history of arrests or incarcerations (3+ mTBIs: 64%), 2.) A lifetime history of arrest but no felony incarceration (3+ mTBIs: 34%), and 3.) A lifetime history of felony incarceration (3+ mTBIs: 2%). Ordinal regression analyses revealed that performance on a working memory task (Digit Span; b= 0.024, p= .041; OR= 1.024) was significantly associated with increased CJ involvement after adjusting for age, education, service status, and mTBIs. Performance on measures of processing speed (Trails A), set-shifting (Trails B), and inhibition (Flanker) were not significantly associated with CJ involvement. Number of mTBIs was significantly and positively associated with level of CJ involvement in all four models; Digit Span (p= .016), Trails A (p= .016), Trails B (p= .020), and Flanker (p= .008).Conclusions:Performance on most measures of executive functioning was not significantly associated with CJ involvement in this large, representative sample of V/SM who served in combat. Although performance on a working memory task was significantly associated with CJ involvement, the size of the effect was small and the association was in the opposite direction as expected. Number of mTBIs was significantly associated with level of CJ involvement, indicating that sustaining multiple mTBI may be linked to greater risk of CJ involvement. These findings suggest that social and psychological factors beyond executive dysfunction may better explain the relationship between history mTBIs and CJ involvement. Some aspects of military service and veteran status, such as interdisciplinary treatment for brain injury and physical, mental, and psychosocial health needs, may be protective against previously identified risk factors for arrest (e.g., deficits in executive functioning). Contextualizing mTBI within the larger behavioral health profile of V/SM, with emphasis placed on intervention for related co-morbidities, may reduce the impact of previous arrest on wellbeing and/or reduce the risk of future CJ involvement.

5 Intraindividual Variability in Processing Speed on Digital Cognitive Assessments Differs by Amyloidosis Status in Cognitively Normal Older Adults

Objective:Intraindividual variability (IIV) is defined as fluctuations in an individual’s cognitive performance over time1. IIV has been identified as a marker of neurobiological disturbance making it a useful method for detecting changes in cognition among cognitively healthy individuals as well as those with prodromal syndromes2. IIV on laboratory-based computerized tasks has been linked with cognitive decline and conversion to mild cognitive impairment (MCI) and/or dementia (Haynes et al., 2017). Associations between IIV and AD risk factors including apolipoprotein (APOE) ε4 carrier status, neurodegeneration seen on brain imaging, and amyloid (Aß) Positron emission tomography (PET) scan status have also been observed1. Recent studies have demonstrated that evaluating IIV on smartphone-based digital cognitive assessments is feasible, has the capacity to differentiate between cognitively normal (CN) and MCI individuals, and may reduce barriers to cognitive assessment3. This study sought to evaluate whether such differences could be detected in CN participants with and without elevated AD risk.Participants and Methods:Participants (n=57) were cognitively normal older adults who previously received an Aß PET scan through the Butler Hospital Memory and Aging Program. The sample consisted of primarily non-Hispanic (n=49, 86.0%), White (n=52, 91.2%), college-educated (M=16.65 years), females (n=39, 68.4%). The average age of the sample was 68 years old. Approximately 42% of the sample (n=24) received a positive PET scan result. Participants completed brief cognitive assessments (i.e., 3-4 minutes) three times per day for eight days (i.e., 24 sessions) using the Mobile Monitoring of Cognitive Change (M2C2) application, a mobile app-based cognitive testing platform developed as part of the National Institute of Aging’s Mobile Toolbox initiative (Sliwinski et al., 2018). Participants completed visual working memory, processing speed, and episodic memory tasks on the M2C2 platform. Intraindividual standard deviations (ISDs) across trials were computed for each person at each time point (Hultsch et al., 2000). Higher ISD values indicate more variability in performance. Linear mixed effects models were utilized to examine whether differences in IIV existed based on PET scan status while controlling for age, sex at birth, and years of education.Results:n interaction between PET status and time was observed on the processing speed task such that Aß- individuals were less variable over the eight assessment days compared to Aß + individuals (B= -5.79, SE=2.67, p=.04). No main or interaction effects were observed on the visual working memory task or episodic memory task.Conclusions:Our finding that Aß- individuals demonstrate less variability over time on a measure of processing speed is consistent with prior work. No associations were found between IIV in other cognitive domains and PET status. As noted by Allaire and Marsiske (2005), IIV is not a consistent phenomenon across different cognitive domains. Therefore, identifying which tests are the most sensitive to early change is crucial. Additional studies in larger, more diverse samples are needed prior to widespread clinical use for early detection of AD.