Using Virtual Reality for Assessment and Rehabilitation of AD and MCI Patients

Alzheimer's disease (AD) is a primary cause of dementia in the ageing population affecting more than 35 million people around the globe. Acquisition of information in everyday life requires memorization in complex three-dimensional environments. Emerging ICT (information and computer technology) applications based on virtual reality (VR) environments can lead to a behavior modification as they provide a photorealistic virtual environment (VE). This chapter provides a selective overview of the empirical evidence available along last five years on the use of virtual reality (VR) to promote everyday life skills and cognitive impairment mitigation of AD patients. Virtual reality allows us to identify and treat deficits in memory that are relevant to everyday life yet not detectable with list learning. Articles related to virtual reality have been divided in two categories according to their use: whether for assessment and diagnostic or rehabilitative purposes. Clinical implications were critically discussed. Suggestions for future research and practice will also be provided.

Working Memory and Language Contribution to Verbal Learning and Memory in Drug-Resistant Unilateral Focal Temporal Lobe Epilepsy

We aimed to investigate the working memory (WM) and language separate contributions to verbal learning and memory in patients with unilateral drug-resistant temporal lobe epilepsy (drTLE); additionally, we explored the mediating role of WM on the relationship between the number of antiepileptic drugs (AEDs) and short-term verbal memory. We retrospectively enrolled 70 patients with left (LTLE; n = 44) and right (RTLE; n = 26) drTLE. About 40 similar (age and education) healthy controls were used to determine impairments of groups at WM, language (naming and verbal fluency), and verbal learning and memory (five trials list-learning, story memory—immediate recall). To disentangle the effect of learning from the short-term memory, we separately analyzed performances at the first trial, last trial, and delayed-recall list-learning measures, in addition to the total learning capacity (the sum of the five trials). Correlation and regression analyses were used to assess the contribution of potential predictors while controlling for main clinical and demographic variables, and ascertain the mediating role of WM. All patients were impaired at WM and story memory, whereas only LTLE showed language and verbal learning deficits. In RTLE, language was the unique predictor for the most verbal learning performances, whereas WM predicted the results at story memory. In LTLE, WM was the sole predictor for short-term verbal learning (list-learning capacity; trial 1) and mediated the interaction between AED number and the performance at these measures, whereas language predicted the delayed-recall. Finally, WM confounded the performance at short-term memory in both groups, although at different measures. WM is impaired in drTLE and contributes to verbal memory and learning deficits in addition to language, mediating the relationship between AED number and short-term verbal memory in LTLE. Clinicians should consider this overlap when interpreting poor performance at verbal learning and memory in drTLE.

A-186 Preliminary Development of an Embedded Measure of Effort on the Memory Module of the Neuropsychological Assessment Battery (NAB)

Objective The Neuropsychological Assessment Battery (NAB) is an integrated neuropsychological battery for assessing cognitive skills in adults. The current study utilizes performance validity tests (PVTs) to interpret poor effort for scores on the NAB. Method Sample consisted of 306 adult civil litigants referred for a neuropsychological evaluation aged 18 to 85 years with a mean age of 43 years. Education ranged from 8 to 20 years with a mean of 14 years of education. Poor effort was denoted by “failing” 2 or more PVTs versus individuals who did not fail any PVTs (“pass”). Results Independent-samples t-tests were run to determine if there were differences in NAB Memory Module scores between the “pass” and “fail” groups. Multiple scores on NAB Memory Module yielded statistically significant differences. Scores were then used in subsequent ROC curve analyses to determine appropriate cutoff scores with an intent to maximally balance sensitivity and specificity. ROC curve analyses were favorable (i.e., AUC > 0.70) and yielded cut scores for List Learning A Immediate Recall (≤ 18), List Learning A Short Delayed Recall (≤ 6), List Learning A Long Delayed Recall (≤ 4), Shape Learning Immediate Recognition (≤ 15), Daily Living Memory Immediate Recall (≤ 39), Daily Living Memory Delayed Recall (≤ 11), List Learning A Discriminability (≤ 7), and Name/Address/Phone Delayed Recall (≤ 4) with sensitivity values ranging from 0.70 to 0.78 and specificity values ranging from 0.70 to 0.84. Conclusion Results provide preliminary evidence of suggested cutoffs to identify suspected poor effort for various scores in the NAB Memory Module.

A-143 Sorry, I Wasn’t Paying Attention. The Moderating Role of Auditory Attention on the Relationship between Age and Verbal Learning

Objective Attentional difficulties are known to negatively impact learning (Hervey et al., 2004; Alderson et al., 2013). This study builds upon previous work examining the effect of sustained visual attention as a moderator of age and learning (Thomas et al., 2019) by examining performance on an auditory attention measure as a moderator of the relationship between age and performance on a verbal list-learning task. Method Archival data from 424 adults (Mage = 36.01, SD = 15.13) were collected at an outpatient clinic. Auditory attention was assessed via the Brief Test of Attention (BTA) raw score. Learning was assessed via the California Verbal Learning Test (CVLT-II) total T-Score (Trials 1–5). Results Results of a hierarchical linear regression indicated a significant effect between BTA and learning, (β = 0.287, F(1, 422) = 17.993, p < 0.001, ΔR2 = 0.078). There was no significant effect between age and learning, (β = 0.022, F(1, 422) = 0.204, p = 0.652, ΔR2 = 0.000). Additional results from a simple moderated regression analysis indicated a significant overall model between age, learning and BTA (F(3, 420) = 15.749, p < 0.001, ΔR2 = 0.1011) with BTA having a significant positive interaction effect on the relation between age and learning (β = 0.816, F(1, 420) = 10.436, p = < 0.001, ΔR2 = 0.022). Conclusion Sustained attention has been shown to be an important consideration when assessing verbal learning and memory performance. Present results demonstrate that when accounting for age, auditory attention is a significant positive predictor of performance on measures of verbal learning. Additionally, confirming prior research, performances on auditory attention and verbal learning measures are positively correlated.

A-82 Neurocognitive Improvement after Intra-Arterial Bevacizumab for Steroid-Refractory Radiation Necrosis of the Brain

Objective Evaluate neurocognitive change after single low-dose targeted intra-arterial (IA) bevacizumab in patients with brain radiation necrosis. Methods Phase II, single-arm, prospective trial. 10 adults underwent targeted 2.5 mg/kg IA bevacizumab. Neurocognitive indices (Neuropsychological Assessment Battery® and Wechsler Test of Adult Reading) were measured at baseline and 12-months to document performance in 5 domains: Attention, Language, Learning and Memory, Visuospatial, and Executive Function. Clinical indices also quantified. Data (mean ± SD, 95% confidence interval [CI], Cohen’s d) were analyzed using paired t tests. Null hypothesis rejected for p < 0.05. Results At baseline, Numbers-&-Letters Speed T-score (38.2 ± 10.7) indicated decreased processing speed consistent with sub-cortical pattern of illness. All other baseline neurocognitive indices were within normalized means (image). 12-months post-treatment, Numbers-&-Letters Errors T-score increased by 6.0 ± 4.9 [95%CI 1.9,10.1] (t = 3.464, d = 1.225, p = 0.010). List-Learning List-Long-Delayed-Recall T-score increased by 9.0 ± 5.6 [95% CI 4.3,13.7] (t = 4.520, d = 1.598, p = 0.003) and Design-Construction T-score increased by 3.5 ± 4.1 [95%CI 0.04,7.0] (t = 2.391, d = 0.845, p = 0.048). Volume of radiation necrosis decreased by 74.4 ± 14.7% (t = −3.308, d = 1.169, p = 0.013). Headache decreased by 84.4 ± 18.2% (t = −3.495, d = 1.236, p = 0.010). 0/10 died or exhibited AEs attributed to bevacizumab. 2/10 patients experienced radiation necrosis recurrence at months 10 and 11, respectively. Conclusions Single low-dose intra-arterial targeted bevacizumab led to durable neuropsychological performance increase in memory retrieval and visuospatial ability consistent with improvement in sub-cortical function. To our knowledge this is the first prospective report of this novel approach in adults. Clinical improvements mirrored neuropsychologic improvements. Randomized trials are needed comparing targeted low-dose IA bevacizumab to multi-cycle IV bevacizumab at higher doses to determine which is best alternative in brain radiation necrosis.

Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P <0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile ( P =0.015). Lower performance was attributed largely to Word List Recall ( P <0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, P ≤0.01). The scores for left versus right carotid disease were similar. Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02089217.