Psychoeducational Interventions for Adults With Level 3 Autism Spectrum Disorder: A 50-Year Systematic Review There is face validity to the expectation that adults with level 3 autism spectrum disorder (ASD–3) will benefit from a range of psychoeducational interventions. This paper reviews the empirical evidence supporting the effectiveness of these interventions, many of which are currently used in clinical settings. We reviewed 56 peer-reviewed studies of psychoeducational interventions for adults with ASD–3, written in English and since 1968, that met our criteria. The reviewing team included educators, clinicians, researchers, and a biostatistician. The available literature was limited, and most, if not all, of the studies presented some significant methodological limitations. When using Cochrane’s criteria to assess seven key outcome domains—activities of daily living, aggressive/destructive behaviors, emotional functioning, language/communication skills, self-injurious behaviors, stereotypy/mannerisms, and vocational skills—we found only moderately reliable evidence to support the effectiveness of interventions designed to improve emotional functioning in adults with ASD–3. The reliability of evidence relevant to the six other outcome domains was rated as low or very low. Based on this review, we suggest directions for future study of interventions for adults with ASD–3, including topics, subpopulations, and approaches that should be explored. We also propose some crucial changes in how future studies regarding this population should be designed, analyzed, and documented, while balancing clinical considerations with scientific/educational utility.

Insomnia-related Memory Impairment in Individuals With Very Complex Chronic Pain Objective: To investigate the specific effect of insomnia on neuropsychological functioning in patients with very complex chronic pain. Background: Individuals with insomnia disorder or chronic pain often experience cognitive deficits, with both conditions appearing to correlate with impairments in neuropsychological functions. As insomnia often occurs comorbid with chronic pain, distinguishing the differential effects of these two syndromes on an individual’s neuropsychological functioning can be challenging. Comorbid depressive symptoms in these individuals, which may also affect cognitive function, may further obscure the associations between chronic pain, insomnia, and the neuropsychological profile. Methods: The neuropsychological function of 22 individuals with very complex chronic pain was assessed using specialized tests examining aspects of memory and executive functioning. The severity of insomnia, depression, and anxiety was measured using questionnaires, and pain levels were assessed using a visual analog scale. Pain medications were transformed to the morphine-equivalent daily dose. Results: Insomnia severity was found to predict memory function, accounting for 32.4% of the variance: A 1 SD increase in insomnia severity decreased memory function by 0.57 SD. The negative correlation between insomnia and memory was significant even after controlling for pain level, morphine-equivalent daily dose, and comorbid levels of anxiety and depression. Conclusions: Insomnia severity independently predicted memory function in patients with very complex chronic pain, even after controlling for other factors known to impair cognitive function. Insomnia may possibly explain some of the cognitive impairments related to chronic pain; thus, screening for, and treating, sleep disturbances may be a central aspect of chronic pain rehabilitation.

Effects of a Mixed Reality-based Cognitive Training System Compared to a Conventional Computer-assisted Cognitive Training System on Mild Cognitive Impairment: A Pilot Study Background: Mixed reality (MR) technology, which combines the best features of augmented reality and virtual reality, has recently emerged as a promising tool in cognitive rehabilitation therapy. Objective: To investigate the effectiveness of an MR-based cognitive training system for individuals with mild cognitive impairment (MCI). Methods: Twenty-one individuals aged 65 years and older who had been diagnosed with MCI were recruited for this study and were divided into two groups. Participants in the MR group (n=10, aged 70.5±4.2 years) received 30 minutes of training 3 times a week for 6 weeks using a newly developed MR-based cognitive training system. Participants in the control group (n=11, aged 72.6±5.3 years) received the same amount of training using a conventional computer-assisted cognitive training system. Both groups took the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K) both before and after intervention. To determine the effect of the intervention on cognitive function, we compared the difference in each group’s CERAD-K scores. Results: There was a statistically significant interaction between intervention (MR group vs control group) and time (before vs after intervention) as assessed by the Constructional Recall Test. The individuals with MCI who participated in the MR training showed significantly improved performance in visuospatial working memory compared with the individuals with MCI who participated in the conventional training. Conclusion: An MR-based cognitive training system can be used as a cognitive training tool to improve visuospatial working memory in individuals with MCI.

Cognitive and Behavioral Changes in Patients Treated With Droxidopa for Neurogenic Orthostatic Hypotension: A Retrospective Review Background: Droxidopa is a norepinephrine precursor that improves symptoms of neurogenic orthostatic hypotension in conditions such as Parkinson disease, multiple system atrophy, and pure autonomic failure by inducing a pressor effect. Unlike other pressor agents, droxidopa crosses the blood-brain barrier; however, its central effects are, as of yet, uncharacterized. Objective: We present the results of a retrospective cohort study examining cognitive and behavioral side effects linked to droxidopa therapy. Methods: We performed a review of 101 patients who had been treated with droxidopa at an academic tertiary care center and identified cases of cognitive and behavioral changes associated with the therapy. Results: We identified six patients who had developed cognitive and behavioral symptoms, including memory difficulties, confusion, mania, and irritability, shortly after droxidopa initiation. All six patients displayed symptoms of synucleinopathy, manifesting with autonomic failure, rapid eye movement sleep behavior disorder, and parkinsonism. Patients had no significant cognitive or behavioral symptoms before droxidopa initiation. Behavioral disturbances were observed early in the droxidopa titration period and at relatively low doses. Symptoms resolved with dose reduction in four patients, and droxidopa was discontinued in two patients due to persistent irritability. No other medical comorbidities or alternative etiologies were identified to explain the symptoms. Conclusions: Droxidopa is designed to act peripherally as a pressor agent but may also exert important central effects. We hypothesize that the cognitive and behavioral manifestations observed in the patients with orthostatic hypotension resulted from an “overdose” of key noradrenergic networks linking orbitofrontal and mesolimbic regions.

Relationship Between Cognitive-Behavioral Impairment and Clinical and Functional Parameters in ALS and Reliability of the Edinburgh Cognitive and Behavioural ALS Screen to Assess ALS: Preliminary Findings Background: Although it is widely recognized that a high percentage of individuals with amyotrophic lateral sclerosis (ALS) have cognitive and behavioral impairment, the associated clinical and functional parameters remain unknown. ALS is typically assessed via screening tests, such as the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Objective: To investigate the relationship between cognitive-behavioral impairment and other clinical and functional parameters and to compare the assessment results from a set of standardized neuropsychological tests with those from the ECAS. Methods: Forty individuals with ALS participated in the study. We assessed attention, memory and learning ability, and executive function using a set of standardized neuropsychological tests and the ECAS. Sociodemographic variables, time since onset of symptoms, time since diagnosis, and functional respiratory values were recorded. Results: No relationship was found between time since onset of symptoms and time since definitive diagnosis and either attention (P=0.206, 0.314, respectively), memory and learning ability (P=0.618, 0.692), or executive function (P=0.844, 0.583). The set of standardized neuropsychological tests identified an impairment in executive function in 29% of the participants, whereas the ECAS identified it in 89%. Conclusions: We found no relationship between cognitive-behavioral impairment and time since onset of symptoms nor time since ALS diagnosis. Because the ECAS does not correctly reflect the executive function of individuals with ALS, function-specific neuropsychological tests are preferred. Test selection must take into account individuals’ physical characteristics and their consequent ability to respond gesturally or orally.

Relationship Between mTOR Signaling Activation and Postoperative Neurocognitive Disorder in Aged Rats Background: Although incidence rates of postoperative neurocognitive disorder (PND) in aged individuals following noncardiac major surgery are rising as individuals are living longer, the mechanism of PND remains poorly understood. We wondered if mammalian target of rapamycin (mTOR) signaling might be associated with PND since mTOR controls some essential intracellular events. Objective: To investigate whether surgery activates the mTOR signaling pathway in aged rats, leading to PND, and whether the mTOR inhibitor, rapamycin, can be used to alleviate PND. Methods: We randomly assigned aged rats to four groups: normal control (C), isoflurane (I), surgery (S), and rapamycin (R). Then, we anesthetized Groups I, S, and R, following which, Groups S and R underwent a splenectomy. After surgery, Group R was administered rapamycin. We used the Morris water maze to test the rats’ spatial learning and memory after surgery. Results: In Group S, escape latency (ie, the time to find the platform) was markedly higher, and the ratio of swimming time in the target quadrant was lower, compared to the other groups. In Group R, escape latency was markedly lower as compared with Group S, and the ratio of swimming time in the target quadrant was higher. Conclusions: Our results indicate that an altered mTOR signaling pathway after a splenectomy causes PND in aged rats, which can be alleviated by rapamycin.

Changes in Cognitive Performance With Age in Adults With Multiple Sclerosis Background: Cognitive impairment is one of the most common consequences of multiple sclerosis (MS), yet there is a shortage of data regarding how cognition changes during the life span of individuals with MS. This information is of increasing importance given the growing proportion of older adults with MS. Objective: To study possible changes in cognitive function in correlation with increasing age in individuals with MS. Methods: Participants (N=129) were recruited and a priori allocated into one of three age groups (young, middle-aged, and older). All participants completed the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) during a single laboratory testing session. The BICAMS measures cognitive processing speed as well as verbal and visuospatial learning and memory. Results: A multivariate analysis of variance indicated that cognitive function significantly differed by age group, and these differences were not explained by amount of physical activity, years of education, years since diagnosis, or race. Older adults displayed significantly worse cognitive processing speed than young and middle-aged adults. The older and middle-aged adults also demonstrated significantly worse visuospatial learning and memory than the younger adults. Effect sizes indicated that cognitive processing speed and verbal learning and memory were more affected in late adulthood than early adulthood, whereas visuospatial learning and memory was affected similarly in early and late adulthood. Conclusions: Older adults with MS demonstrated significant impairments in cognitive function compared to young and middle-aged adults with MS. Future studies should determine the predictors of cognitive decline in this age cohort.

Vertical and Radial Attentional Neglect in Corticobasal Syndrome Corticobasal degeneration (CBD), a tau-related neurodegenerative disease, is characterized by limb rigidity, dystonia, myoclonus, apraxia, and cognitive deficits. We report a patient with probable corticobasal syndrome, a major phenotype of CBD, who revealed both lower vertical and proximal radial attentional neglect on line bisection tests. Brain imaging revealed bilateral parietal atrophy with hypometabolism in the bilateral parietal, dorsolateral prefrontal, and premotor cortices. Bilateral impairment in the dorsal attentional network reduces the allocation of spatial attention to lower and proximal space, causing lower vertical and proximal radial attentional neglect. Screening for various types of spatial neglect may be important in tailoring management and rehabilitation strategies for patients with CBD.

Everything in Its Place: First Loves and Last Tales No abstract available

Self-Consciousness and “Split” Brains: The Minds’ I No abstract available