Changes In Neuropsychological Performance Research Articles

Health-Related Quality of Life and Neuropsychological Outcome After EC-IC Bypass Revascularization in Adult Patients With Moyamoya Disease.

Patients with Moyamoya disease (MMD) have an above-average incidence of neuropsychological impairment and psychiatric comorbidities such as depression. Prevalence and correlation with preoperative imaging findings were identified in previous studies, and a reduced health-related quality of life (HRQOL) has been shown. This study investigates changes in neuropsychological performance and HRQOL after revascularization. Thirty-two adult patients with MMD (23 female, 9 male; mean age 39.1 year ±14.7) with revascularization were included in this retrospective cohort study, and their results of structured neuropsychological testing were analyzed preoperatively and 1 year postoperatively. Sensorimotor deficits assessed with the National Institutes of Health Stroke Scale were considered to be possible confounders. Patients with preoperatively poor test results showed improvement in various items such as psychological well-being (95% CI [0.55-2.25], P = .002), vitality (95% CI [0.23-1.68], P = .007), general health perception (95% CI [0.09-1.44], P = .014), psychoticism (95% CI [-12.24 to -4.85], P < .001), and psychomotor processing speed (95% CI [0.10-1.14], P = .010), whereas the intensity of depression fell by a mean of 6.9 points (95% CI [-10.14 to -3.61], P < .001). For patients without preoperative neuropsychological or HRQOL deterioration, preservation of these functions without relevant worsening after revascularization was observed. Significant improvement in vitality, psychological well-being, psychoticism, psychomotor processing speed, and depression were also seen in patients with unchanged National Institutes of Health Stroke Scale. Chronic steno-occlusive cerebral hypoperfusion in patients with MMD not only may lead to neurological deficits but is also associated with neuropsychological impairment, reduced HRQOL, and increased depression. The results of this study show that patients with preoperative neuropsychological deterioration might benefit from revascularization surgery, whereas patients without preoperative impairment continue to remain stable postoperatively. Neuropsychological assessment should be routinely evaluated and considered a relevant variable when determining treatment for patients with MMD.

Longitudinal Changes in Neuropsychological Functioning in Japanese Patients with Myotonic Dystrophy Type 1: A Five Year Follow-Up Study.

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy that causes various symptoms, including those of the central nervous system. Some studies have reported cognitive decline in patients with DM1, although the available evidence is limited. This study aimed to describe longitudinal differences in neuropsychological function in patients with DM1. A total of 66 Japanese adult patients with DM1 were investigated using a neuropsychological battery to assess several cognitive domains, including memory, processing speed, and executive function. The patients underwent neuropsychological evaluation approximately five years after baseline (Times 1 and 2). Thirty-eight patients underwent a second neuropsychological evaluation. The participants in the Time 2 evaluation were younger than those who did not participate in Time 2. Patients showed a decline in the Mini-Mental State Examination, Trail Making Test (TMT), Block Design, and Symbol Digit Modalities Test at Time 2 (P < 0.05). Age at Time 1 was associated with a decline in TMT-A and TMT-B scores (rho = 0.57 and 0.45, respectively). These results suggest a cognitive decline in patients with DM1 and warrant further investigation into the possible effects of age-related changes.

86 Influence of Psychosocial Coronavirus Pandemic Stressors on Neuropsychological Functioning

Objective:The objective of this study was to examine whether novel pandemic-related stressors have any effect on cognitive functioning. This study aimed to examine whether the overall number of pandemic-related stressors, and whether stressor type, are associated with cognitive problems. The coronavirus pandemic, and societal changes to prevent and respond to it, have created novel stressors, including unemployment, social isolation, and health risks. While prior research has focused on the physical and psychological consequences of these stressors, these stressors may also be associated with cognitive impairments. Individuals who have been infected with SARS-CoV-2 and individuals who experience chronic stress are at risk for cognitive impairments, however, research has not yet examined whether pandemic-related stressors not specifically related to infection but to the experience of the pandemic overall, are associated with cognitive deficits. This study evaluated whether pandemic-related psychosocial stressors (financial, health, role/responsibility, and social) were related to cognitive functioning. We hypothesized that individuals with a higher number of pandemic-related stressors will perform worse on cognitive domains of attention, memory, and executive functions, than those with fewer stressors.Participants and Methods:An online survey recruited participants (A/=19), of whom 89.5% were female, and the average age was 34 years (SD=15.7), to complete an online neuropsychological battery. Participants first completed questionnaires on the coronavirus pandemic, demographic characteristics, and completed the BDI-II and the BAI. An online neuropsychological battery was administered to participants over Zoom consisting of various neuropsychological tests, including the RAVLT, story memory, digit span, FAS, animal fluency, a go-no/go task, the Stroop, and the NAART-R.Results:A majority of participants (89.5%) experienced one or more coronavirus pandemic stressors, with only two participants reporting no coronavirus stressors. A majority of participants experienced at least one social stressor (57.9%), role/responsibility stressor (63.2%), and health stressor (52.6%), with financial stressors (47.4%) experienced by just fewer than half of participants. Pearson’s correlations showed significant negative correlations between stressors and performance on several neuropsychological tests. Specifically, social, health, and total stressors were associated with significantly poorer performance on digit span backwards and trials of the RAVLT (i.e., Trials 15, delayed recall, recognition) (ps&lt;.05). Social stressors, health stressors, and total pandemic stressors were significantly associated with poorer performance on measures of working memory, processing speed, verbal learning, and verbal memory.Conclusions:While small sample size limits the power and generalizability of these findings, this study highlights the need to investigate the cognitive effects of pandemic-related stressors. An expanded coronavirus questionnaire would be beneficial as the current questionnaire may have not captured all stressors of the pandemic, or level of severity, that could potentially contribute to changes in neuropsychological function. Pandemic-related stressors have spread into many areas of everyday life and the consequences that have stemmed from these stressors seem to play a negative role on the general wellbeing of individuals and also show an effect on psychological and neuropsychological functioning. This study illustrates the need for an expanded response to health crises, as the negative results of this pandemic have not been solely affecting physical health.

A-01 Trait Mindfulness Gains Associated with Executive Functioning Improvements Following Physical Exercise in Older Adults

Abstract Purpose Although there are certain injury risks associated with sports participation (e.g., concussion), there are also neuropsychological benefits relating to physical activity. Evidence suggests that trait mindfulness (TM) may contribute to the neuropsychological benefits of physical activity and exercise, including those pertaining to executive functioning (EF) and mood. The present study aimed to investigate the degree to which changes in TM accounted for changes in neuropsychological functioning following a remote physical exercise training program for older adults. It was hypothesized that increases in TM would predict improvements in self-reported EF and symptoms of depression and anxiety. Methods As part of a larger RCT, 43 older adults (70% females, 65-81 years-old) from across Canada completed an online assessment measuring TM, EF, and mood before and after engaging in an 8-week remote physical exercise training program. Results Linear regression analyses showed that pre-post changes in TM explained a significant proportion of variance in self-reported changes in EF, r2=.18, F(1,24)=5.11, p&amp;lt;.05, but did not for symptoms of depression, r2=.06, F(1,24)= 1.53, p= 23 or anxiety, r2=.04, F(1,24)=1.08, p=.31. More specifically, bivariate correlations demonstrated that gains in TM were significantly associated with increases in reported impulse control, r=.48, p=.01, and empathy, r=.42, p&amp;lt;.05. Conclusions These results suggest that for older adults engaging in exercise, gains in trait mindfulness may be associated with benefits to certain aspects of executive functioning. These findings also invite sports neuropsychologists to consider level of mindfulness when evaluating individuals (e.g., athletes) engaged in exercise.

Cognitive inhibition deficit in long COVID-19: An exploratory study.

An increasing number of research studies point toward the importance and prevalence of long-term neurocognitive symptoms following infection with COVID-19. Our objectives were to capture the prevalence of cognitive impairments from 1 to 16 months post-COVID-19 infection, assess the changes in neuropsychological functions over time, and identify factors that can predict long-term deficits in cognition. A cross-sectional research design was adopted to compare four sub-samples recruited over a 16-month timeframe (1-4, 5-8, 9-12, and 13-16 months). Phone interviews were conducted at least 6 weeks after being infected by COVID-19. Sociodemographic and clinical questionnaires were administered followed by standardized neurocognitive and psychological tests and health questionnaires screening cognitive symptoms, anxiety, depression, fatigue, and autonomy. Regarding general health questionnaires, 55.2% of the 134 participants had symptoms of psychiatric illness, while 21.6% of patients had moderate-to-severe anxiety or depression. Cognitive efficiency was diminished in 19.4% of our population. Executive dysfunction was screened in 56% of patients, and an impairment of cognitive flexibility and inhibition was revealed in 38.8%. Depression, hospital or intensive care unit (ICU) admission, and the duration of hospital or ICU stay were associated with an inhibition deficit. The duration elapsed from the initial infection, and the neurocognitive assessment was not associated with a decrease in inhibition deficit. The prevalence of cognitive impairments, other than inhibition deficit, tended to decrease during the study period. This study supports the extensive literature on the cognitive and neuropsychiatric sequelae of COVID-19 and highlights long-lasting inhibition deficits, while other cognitive functions seemed to improve over time. The severity of infection could interact as a catalyst in the complex interplay between depression and executive functions. The absence of a relation between inhibition deficits and sociodemographic or medical factors reinforces the need for cognitive screening in all COVID-19 patients. Future research should focus on inhibition deficits longitudinally to assess the progression of this impairment.

Associations of Olfaction With Longitudinal Trajectories of Brain Volumes and Neuropsychological Function in Older Adults.

Olfactory function declines with aging, and olfactory deficits are one of the earliest features of neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. Previous studies have shown that olfaction is associated with brain volumes and cognitive function, but data are exclusively cross-sectional. We aimed to examine longitudinal associations of olfaction with changes in brain volumes and neuropsychological function. In the Baltimore Longitudinal Study of Aging, we chose the first assessment of olfaction to examine the associations with retrospective and prospective changes in neuropsychological performance and brain volumes in participants aged 50 years or older using linear mixed-effects models, adjusted for demographic variables and cardiovascular disease. Olfaction was measured as odor identification scores through the 16-item Sniffin' Sticks. We analyzed data from 567 (58% women, 42% men, 27% Black, 66% White, and 7% others) participants who had data on odor identification scores and brain volumetric MRI (n = 420 with retrospective repeats over a mean of 3.7 years, n = 280 with prospective repeats over a mean of 1.2 years). We also analyzed data from 754 participants (56% women, 44% men, 29% Black, 65% White, and 6% others) with neuropsychological assessments (n = 630 with retrospective repeats over a mean of 6.6 years, n = 280 with prospective repeats over a mean of 1.5 years). After adjustment, higher odor identification scores were associated with prior and subsequent slower brain atrophy in the entorhinal cortex (β ± SE = 0.0093 ± 0.0031, p = 0.0028 and β ± SE = 0.0176 ± 0.0073, p = 0.0169, respectively), hippocampus (β ± SE = 0.0070 ± 0.0030, p = 0.0192 and β ± SE = 0.0173 ± 0.0066, p = 0.0089, respectively), and additional frontal and temporal areas (all p < 0.05). Higher odor identification scores were also associated with prior slower decline in memory, attention, processing speed, and manual dexterity and subsequent slower decline in attention (all p < 0.05). Some associations were attenuated after exclusion of data points at and after symptom onset of cognitive impairment or dementia. In older adults, olfaction is related to brain atrophy of specific brain regions and neuropsychological changes in specific domains over time. The observed associations are driven, in part, by those who developed cognitive impairment or dementia. Future longitudinal studies with longer follow-ups are needed to understand whether olfactory decline precedes cognitive decline and whether it is mediated through regionally specific brain atrophy.

Neurocognitive moderation of repetitive transcranial magnetic stimulation (rTMS) effects on cannabis use in schizophrenia: a preliminary analysis

Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for cannabis use disorder in schizophrenia; however, gaps in the literature remain as to the potential role of neurocognitive functioning in treatment response. We evaluated the moderating role of select cognitive functions including baseline executive functioning, verbal memory, and sustained attention, and we explore the mediating role of changes in task performance on changes in cannabis use in both active and sham rTMS groups. Participants underwent high-frequency (20 Hz) rTMS applied to the bilateral dorsolateral prefrontal cortex 5x/week for 4 weeks. Weekly self-report of cannabis use and semi-quantitative urinary carboxy-tetrahydrocannabinol levels were recorded. A neurocognitive battery assessing verbal memory, visuospatial working memory, verbal working memory, sustained attention, delayed discounting, and complex planning was administered pre- and post-treatment. Better baseline performance on tasks assessing sustained attention, delayed discounting, and complex planning moderated the extent to which participants in the active group reduced cannabis use. There were no significant indirect pathways between treatment, changes in neuropsychological performance, and changes in cannabis use; however, active rTMS improved complex planning and sustained attention. These preliminary findings suggest that there is a moderating role of sustained attention, delayed discounting, and complex planning on the effects of rTMS on cannabis use. Further, mediation models suggest rTMS may exert direct effects on cannabis use independent of its effects on cognitive functioning in people with SCZ. Trial Registration: clinicaltrials.gov: NCT03189810.

Brief Report: Undercarboxylated Osteocalcin Is Associated With Cognition in Women With and Without HIV.

Bone loss and cognitive impairment are common in women living with HIV (WLWH) and are exacerbated by menopause. Bone-derived undercarboxylated osteocalcin (ucOCN) and sclerostin appear to influence cognition. The current study investigated whether the circulating levels of these 2 proteins are associated with cognition in midlife WLWH and demographically similar HIV seronegative women. Plasma samples from women enrolled in a musculoskeletal substudy within the Women's Interagency HIV Study were used to measure ucOCN and sclerostin. A neuropsychological (NP) test battery assessing executive function, processing speed, attention/working memory, learning, memory, verbal fluency, and motor function was administered within 6 months of musculoskeletal enrollment and every 2 years after (1-4 follow-up visits per participant). A series of generalized estimating equations were conducted to examine the association between biomarkers and NP performance at the initial assessment and over time in the total sample and in WLWH only. Primary predictors included biomarkers, time, and biomarker by time interactions. If the interaction terms were not significant, models were re-run without interactions. Neither biomarker predicted changes in NP performance over time in the total sample or in WLWH. ucOCN was positively associated with executive function in the total sample and in WLWH and with motor skills in WLWH. ucOCN was negatively associated with attention/working memory in the total sample. There were no significant associations between sclerostin and NP performance. The current study suggests an association between bone-derived ucOCN and cognition in women with and without HIV infection.

World Federation of Athletic Training and Therapy World Congress 2022 Peer-Reviewed Track Abstracts, May 5–7, 2022, Winnipeg, Manitoba, Canada

World Federation of Athletic Training and Therapy World Congress 2022 Peer-Reviewed Track Abstracts, May 5–7, 2022, Winnipeg, Manitoba, Canada

Integration of standardized brain volumetric and neuropsychological assessment data: Conceptual background and preliminary data

<h3>Introduction</h3> NeuroQuant (NQ) is the first FDA-approved medical software to automate and standardize the analysis of brain MRI volumetrics. Such measurements may hold significant value in diagnostic settings by reducing the subjectivity of neuroradiological interpretations. However, NQ reports currently lack any accompanying clinical interpretation, thus limiting its clinical utility. Therefore, identifying reliable cognitive correlates of NQ volumetric data is an important target of investigation in order to enhance clinical applicability. Using NQ data in this way may be particularly valuable within comprehensive assessments aimed at characterizing age-related changes in neuropsychological functioning – one of the overarching aims of our broader though still nascent NQ research program. This poster will provide a conceptual and methodological overview of our NQ program, including a proposed investigation into how volumetric measurements in certain medial-temporal subregions, namely hippocampus, parahippocampus, and entorhinal cortex, predict specific auditory-verbal and visuospatial memory processes commonly assessed in clinical evaluations (i.e., encoding, retrieval, and storage/retention). Though all three regions are heavily intertwined in the processing of memory, previous research suggest these regions may be differentially involved in particular memory processes. However, this has not been examined using standardized volumetric measurements. We present results from a preliminary correlational analysis focused on the association between NQ data from those medial temporal regions and different levels of just auditory memory function in a small, mixed older adult clinical sample. We expect all three brain regions to be differentially associated with the encoding, retrieval, and storage levels of auditory memory. This particular question has been prioritized given its potential value in enhancing dementia/memory assessments, specifically for Alzheimer's disease (AD). Understanding the associations between key brain structures and different types of memory function will aid in the development of more robust and multi-faceted AD diagnostic protocols that incorporate NQ data. <h3>Methods</h3> Subjects are comprised of a mixed clinical sample of older adults who have undergone both neuropsychological testing and structural brain MRI+NQ as part of a comprehensive clinical evaluation in the McLean Hospital Memory Disorders Assessment Clinic. We will apply linear mixed effects models to investigate the association between NQ-derived volumetric measurements in three medial temporal regions across both hemispheres (hippocampus, parahippocampus, and entorhinal cortex) and different levels of verbal and visuospatial memory function (encoding/registration, retrieval, and storage/retention) measured by the California Verbal Learning Test (CVLT-II), Logical Memory (LM), and Rey Complex Figure Test (RCFT). For the current preliminary analysis, however, we present a more narrowly focused bivariate correlational analysis (Spearman rank-order) of CVLT-II data in a small subset of patients (N=6), with NQ data being aggregated across hemispheres. Analyses were performed using R (version 4.1.1). <h3>Results</h3> Six patients (5 female) ranged in age from 72 to 83 years, with an average of 15.5 ± 3.5 years of education. Patients had a mix of major depressive disorder, generalized anxiety disorder, bipolar II disorder, and mild/major neurocognitive diagnoses, with all but 1 patient having comorbid diagnoses. There was a positive correlation between CVLT-II long delay free recall – a measure of memory retrieval – and total entorhinal cortex volume that trended towards significance (ρ=0.79, <i>p</i>=0.059). There were no other significant correlations (all <i>p</i> > 0.1). <h3>Conclusions</h3> The marginally significant correlation between CVLT-II long delay free recall and entorhinal cortex volume suggests this region may be more strongly related to delayed retrieval compared to other memory processes. However, with such a small subject size, these findings must be viewed as highly preliminary and interpreted accordingly. Nonetheless, they support our plan to pursue more sophisticated analyses using linear mixed effects models once more data are available. Validating the associations between structural memory hubs and cognitive function with cutting-edge NQ imaging software lays the groundwork for future projects implementing NQ as a standard of practice in the clinical assessment of age-related cognitive disorders. Additional planned research questions will also be discussed, such as examining associations between cognitive data from commonly used neuropsychological tests and NQ volumetrics in specific connectivity hubs that are critical to broader neural network function. <h3>This research was funded by</h3> Unfunded.

The influence of social support on cognitive health in older women: a Women’s Health Initiative study

ABSTRACT Social support is associated prospectively with cognitive decline and dementia among the elderly; however, little is known about the impact of social support on healthy neurological aging. The current study investigates whether perceived social support has an influence on neurological health among a large sample of healthy postmenopausal women. Social support and neuropsychological outcomes were measured annually for six years through the Women’s Health Initiative Study of Cognitive Aging. In postmenopausal women, higher perceived social support was associated with significantly better overall neuropsychological functioning at baseline, especially in the domains of short-delay figural memory, short-delay verbal memory, and semantic fluency. No significant associations were found between social support and longitudinal changes in neuropsychological function over a median follow-up period of six years. Additionally, there was no significant relationship between social support and regional brain volumes. These findings suggest that social support is related to performance in a subset of neuropsychological domains and contributes to the existing literature that points to the importance of social support as a modifiable lifestyle factor that has the potential to help protect against the decline of cognitive aging, specifically among older adult women.

Lateralized Effect of Thalamic Deep Brain Stimulation Location on Verbal Abstraction.

Regionalized thalamic activity has been implicated in language function, and yet the effect of thalamic deep brain stimulation (DBS) on language-related clinical outcomes is underexplored. The objective of this study was to determine if the location of stimulation within the thalamus correlates with changes in language-related neuropsychological outcomes following DBS for essential tremor. Thirty patients with essential tremor underwent comprehensive neuropsychological evaluations before and after DBS surgery targeting the ventral intermediate nucleus of the thalamus. Changes in neuropsychological functions were evaluated. The relationships between language-related outcomes and stimulation location were assessed using both categorical and linear methods. Any significant results were further validated using linear discriminant analysis. Most neuropsychological functions remained unchanged at the group level. However, outcome on a measure of verbal abstraction was significantly dependent on stimulation location along the anterior-posterior axis within the left ventral lateral thalamus, with anterior stimulation associated with reduced verbal abstraction performance. This result was supported by linear discriminant analysis, which showed that stimulation locations with improved and reduced verbal abstraction function were best separated by a vector nearly parallel to the anterior-posterior axis. No stimulation location dependence was found for verbal abstraction outcome in the right thalamus or for outcomes of other language functions in either hemisphere. We demonstrate an effect of thalamic DBS on verbal abstraction as a function of left thalamic topography. This finding provides clinical evidence for the lateralization and regionalization of thalamic language function that may be relevant for understanding nonmotor effects of stimulation. © 2021 International Parkinson and Movement Disorder Society.

The effects of proton pump inhibitors on neuropsychological functioning

Objective The current study investigated the effects of proton pump inhibitor use and apolipoprotein ε4 carrier status on changes in neuropsychological functioning in healthy adults with familial risk factors for dementia. Methods As part of the Wisconsin Registry for Alzheimer’s Prevention study, 1,573 subjects were administered questionnaires on their medical history, gave blood samples, and were administered neuropsychological assessments during four visits over a 10–15 year period. Linear mixed models assessed if non-users, subjects who stopped, started, or consistently used proton pump inhibitors differed in changes in working memory, verbal memory, psychomotor speed, and cognitive flexibility. Results The models did not yield significant main effects for proton pump inhibitor use or interaction effects between proton pump inhibitor use and apolipoprotein ε4 carrier status on a decline in memory or processing speed. An interaction effect suggested stopping a proton pump inhibitor may be protective against declines in cognitive flexibility among non-carriers. Conclusions Although stopping a proton pump inhibitor use may have mild protective effects on executive functioning for non-apolipoprotein ε4 carriers, proton pump inhibitor use was not associated with memory decline in a sample of subjects with familial risk factors for dementia.

EEG Brain Wave Dynamics: A Systematic Review and Meta Analysis on Effect of Yoga on Mind Relaxation

Background: Yoga is an ancient Indian science and way of life that is prophylactic, promotive and curative leading to good health: physical, mental, emotional and spiritual. Yogic practices like asana, Pranayama, Dhyana and Meditation are extremely beneficial in maintaining sound health and well-being. In this study we reviewed, synthesized, and analyzed published reports on EEG and other changes in neuro-psychological functions associated with Yoga practice. Methods: Published data till Jun 2020 on topics of Yoga, EEG analysis were included based on PRISM statement guidelines. The data characteristics defined by their objectives, study design, methodology, Yoga interventions, EEG power spectrum and outcomes of the study are presented in this review. The EEG data with mean ± SD was used for statistical analysis. Results: The reviewed studies are heterogeneous and have used different yoga practices (Asana, Pranayama, Dhyana, and Meditation), brain region and brain wave for effect evaluation. Overall, there was increase in the α-EEG and δ-EEG power (μV2), but decrease in θ-EEG in many studies. The improvement in α-EEG power was significant at (p = 0.026). Conclusion: EEG Brain wave analysis is one of the best ways to predict the neuro-cognitive benefits of Yoga practice. After yogic practices there was an increase in delta, alpha and gamma amplitude and duration indicating relaxation following yoga practice.

Neurocognitive Effects of Antiretroviral Initiation Among People Living With HIV in Rural Uganda.

HIV-associated neurocognitive disorders remain prevalent despite effective antiretroviral therapy (ART), but there are limited longitudinal data on people living with HIV (PLWH) in sub-Saharan Africa. We examined neuropsychological (NP) performance in PLWH in a longitudinal study in Uganda. Participants enrolled through the Rakai Community Cohort Study (400 ART-naive PLWH and 400 matched HIV-negative persons) were administered NP assessments. In 2017, PLWH who had initiated ART underwent a 2-year follow-up assessment. Demographically adjusted Z-scores for each NP test were established using data from the HIV- controls. Multivariable linear and logistic regressions were conducted to examine group differences in NP performance. Mixed-effects regressions were conducted to examine ART-related changes in NP outcomes. Of 333 PLWH who returned for their 2-year follow-up visit, 312 (94%) had initiated ART. Those on ART had a mean age of 35.6 years (SD ± 8.5 years) and mean education of 5.4 years (SD ± 3.3 years); 49% were women. ART-associated NP improvements occurred in verbal learning and memory (P's < 0.05), motor (P's < 0.01), and some measures of processing speed (P = 0.002), whereas there were declines in attention/working memory (P's < 0.001) and semantic fluency (P < 0.001). Pre-ART CD4 count and efavirenz use were associated with a more impaired change in NP performance. PLWH in this resource-limited setting showed improved neurocognitive performance on most NP tests after ART initiation. However, the declines in attention/working memory and fluency performance, as well as relationship to efavirenz, warrant further study.

Cognitive complaints by hematopoietic cell transplantation recipients and change in neuropsychological performance over time.

Hematopoietic stem cell transplant (HSCT) recipients are at risk for cognitive decline. Cross-sectional studies show patients' complaints of cognitive decline do not correlate well with concurrently measured objective neuropsychological performance, but rather with emotional variables and health-related quality of life. This longitudinal study investigated whether patient self-report of cognitive status would be concordant with objectively measured neuropsychological performance after accounting for change from their own pre-transplant objective baseline. Pre-HSCT and at 30 and 100days post-HSCT, 46 patients underwent computerized neuropsychological testing (CogState) and completed surveys assessing patient-reported cognitive complaints, emotional symptoms (depression, anxiety), sleep quality, daytime sleepiness, and physical and functional well-being. Correlations were calculated between cognitive complaints and neuropsychological performance (at each time-point and across time-points), as well as all other patient-reported variables. Patient-reported cognitive complaints were largely independent of concurrently assessed objective neuropsychological performance. Uniquely, our longitudinal data demonstrated significant medium to large effect size associations between subjective cognitive complaints post-HSCT with objectively measured change from pre-HSCT in attention, visual learning, and working memory (p < .05-.01). Subjective cognitive complaints post-HSCT were also associated with depression, anxiety, daytime sleepiness and physical well-being (p < .05-.001). Patients appear better able to assess their cognitive functioning relative to their own baseline and changes across time rather than relative to community norms. Thus, patient complaints of cognitive compromise justify further in-depth neuropsychological, emotional, and functional assessment. Future research into relationships between cognitive complaints and neuropsychological performance should account for changes in performance over time.

124 Correlating structure and function to better identify surrogate end points for clinical trial design: a longitudinal clinical and imaging study of primary progressive aphasia

IntroductionMeasuring longitudinal change in white matter tracts offers a highly sensitive way of monitoring the course of a range of neurodegenerative conditions. However, it remains unclear how structural changes correlate with symptom progression. Clinically meaningful outcomes remain a key requirement in therapeutic trial design so imaging biomarkers need to accurately predict these outcomes. Identifying surrogate clinical end points is of particular importance in neurodegenerative conditions where clinical change evolves slowly. To address this the current study aims to identify potential surrogate end points by assessing correlations between clinical and neuroimaging measures.Methods30 patients meeting consensus criteria for a diagnosis of primary progressive aphasia underwent longitudinal imaging and neuropsychological assessments at baseline and one year. A mixed effects model was designed to test for significant interactions over time between changes in neuropsychological performance and Fractional Anisotropy (FA) in key white matter tracts.ResultsDeclining single word comprehension correlated with reducing FA within bilateral inferior longitudinal fasciculus (ILF), bilateral superior longitudinal fasciculus (SLF) and the genu of the corpus callosum; declining naming ability correlated with reducing FA in the left ILF, right uncinate fasciculus and right SLF; declining word repetition correlated with reducing FA within the left ILF.ConclusionsDeclining neuropsychological scores correlated with longitudinal decline in FA in a number of white matter tracts across an anatomically distributed language network. Correlations between function and structure provide evidence that monitoring structural white matter changes in the tracks identified may have value as a surrogate end point for future clinical trials.

Neuropsychological changes in efavirenz switch regimens.

Efavirenz is associated with side effects involving the central nervous system. However, it remains largely unknown whether switching off EFV improves neuropsychological performance. We utilized data from the Multicenter AIDS Cohort Study (MACS). Participants were categorized by their use of EFV: never on EFV (No EFV), continuously on EFV (No Switch-OFF) and on EFV and then switched off (Switch-OFF). Baseline time points were defined as visits when first neuropsychological data were available. In Analysis 1, we compared neuropsychological and Center for Epidemiological Studies-Depression Scale (CES-D) scores before and after EFV switch in Switch-OFF group, aligning participants at the time of switch. Analysis 2 evaluated trajectory of neuropsychological/CES-D score among the three groups. This analysis included 1989 HIV-seropositive participants with neuropsychological data (1675 in No EFV, 44 in No Switch-OFF, and 270 in Switch-OFF group). At baseline, participants had a median age of 37 years, median CD4 cell count 442 cells/μl, and 22.9% viral suppression rate. In Analysis 1, neuropsychological and CES-D scores did not show clinically significant changes over 2 years prior to and 4 years after switch in Switch-OFF group. In Analysis 2, trends in neuropsychological and CES-D scores in the three different groups did not show significant differences during a median of 3.2 years of follow-up. Discontinuation of EFV is not associated with changes in neuropsychological performance or severity of depression in men. Furthermore, we did not observe differences among participants who were never on EFV, continuously on EFV, and on EFV and then switched off.

Neuropsychiatric Symptoms as Risk Factors for Cognitive Decline in Clinically Normal Older Adults: The Cache County Study

There has been considerable progress in identifying early cognitive and biomarker predictors of Alzheimer's disease (AD). Neuropsychiatric symptoms (NPS) are common in AD and appear to predict progression after the onset of mild cognitive impairment or dementia. The objective of the study is to examine the relationship between NPS in clinically normal older adults and subsequent cognitive decline in a population-based sample. The Cache County Study on Memory in Aging consists of a population-based sample of 5,092 older adults. We identified 470 clinically normal adults who were followed for an average period of 5.73 years. NPS were evaluated at the baseline clinical assessment using the Neuropsychiatric Inventory (NPI). NPI domain scores were quantified as the product of frequency X severity in individual NPI domains, and then summed for the NPI-Total. Neuropsychological measures were collected at baseline and at each subsequent follow-up wave. Linear mixed-effects models assessed the association of NPI-Total, NPI-Depression, and NPI-Anxiety scores (obtained at baseline) on longitudinal change in neuropsychological performance, controlling for age, sex, and education. Baseline NPI-Total score was associated with a more rapid rate of decline in word list memory, praxis recall, and animal fluency. Baseline NPI-Depression was not associated with later decline on any of the cognitive tests, while baseline NPI-Anxiety was associated with decline in Symbol Digit Modality. In conclusion, among clinically normal older adults derived from this population-based study, total burden of NPS was associated with longitudinal cognitive decline. These results add to the evidence that NPS are risk factors for or clinical indicators of preclinical dementia syndrome. Our study was an exploratory study and we did not control for multiple comparisons.

Diffusion tensor imaging based white matter changes and antioxidant enzymes status for early identification of mild cognitive impairment

Mild cognitive impairment (MCI) is an early stage of dementia. The changes in white matter integrity and antioxidant enzymes levels are crucial in onset and progression to Alzheimer’s disease (AD). To elucidate the changes in cognitive performance, white matter integrity, oxidative stress marker, for early detection of prodromal state of AD. Fifty cases of MCI and controls (55-75 years) were subjected to Mini Mental State Examination (MMSE), diffusion tensor imaging (DTI) followed by estimation of superoxide dismutase, glutathione peroxidase and lipid peroxidation in serum of MCI and control population. The MMSE scores of MCI subjects were (28±2 - 22.6±1) as compared with controls (28±1- 29±1). DTI metrics fractional anisotropy (FA) values in right and left frontal lobe, fornix, corpus callosum, while apparent diffusion coefficient (ADC) values in right temporal lobe, hippocampus head, corpus callosum right, and forcep major were significantly altered in MCI as compared with controls. Superoxide dismutase, glutathione peroxidase level were lower while lipid peroxidation marker malondialdehyde (MDA) was increased in patients with MCI as compared with controls. The study emphasized that changes in neuro-psychological performance, white matter integrity and antioxidant enzymes level provide early signature for diagnosis of MCI.