Mild Deficits Research Articles

Atypical Alzheimer’s disease: new insights into an overlapping spectrum between the language and visual variants

AbstractBackgroundThe language and visual variants are two common clinical phenotypes of atypical Alzheimer’s disease (AD). There are reports of overlap between these clinical phenotypes, however, the extent and frequency of overlap, and its neuroanatomical underpinnings remain unclear.MethodEighty‐two patients with biomarker‐confirmed AD who presented with either predominant language (n = 34) or visuospatial/perceptual (n = 48) deficits were recruited by the Neurodegenerative Research Group and underwent neurological and neuropsychological testing, MRI and [18F]flortaucipir‐PET. The clinical examination included testing for simultanagnosia, Gerstmann’s syndrome, ideomotor apraxia, visuospatial‐visuoperceptual function, confrontational naming, sentence repetition and letter and animal fluency. Cut‐points for abnormality were defined for each test and used to classify the following groups: language‐pure (no visual‐function deficit), language‐plus (impaired on one visual‐function), language‐mixed (impaired on two visual‐functions), visual‐pure (no language‐function deficit), visual‐plus (impaired on one language‐function) and visual‐mixed (impaired on two language‐functions). Patterns of relative volume loss and flortaucipir uptake were assessed using SPM12.ResultOf the 82 patients, 11 (13%) were language‐pure, 16 (20%) language‐plus, 7 (8%) language‐mixed, 10 (12%) visual‐pure, 17 (21%) visual‐plus and 21 (26%) visual‐mixed, with no difference in disease duration across groups. Visual deficits in the language‐plus group consisted of mild simultanagnosia in 29%, Gerstmann’s syndrome in 24%, and mild visuospatial deficits. In the language‐mixed group 86% had simultanagnosia and 43% had Gerstmann’s syndrome, with visuospatial‐visuoperceptual deficits comparable to the visual‐pure group. Language deficits in the visual‐plus group consisted of mild anomia and reduced letter and animal fluency. The visual‐mixed group reported naming and repetition deficits, and reduced fluency, comparable to the language‐predominant groups. All three language groups showed left temporal volume loss and flortaucipir uptake, with greater involvement of the parieto‐occipital and frontal lobes in language‐plus and language‐mixed groups. All three visual groups showed occipital volume loss and flortaucipir uptake, with greater involvement of the parieto‐temporal and frontal lobes in visual‐plus and visual‐mixed groups.ConclusionOnly 25% of our cohort showed a pure language or visual presentation, highlighting the high frequency of syndromic overlap in atypical AD and the diagnostic challenge of categorical phenotyping. Syndromic overlap was associated with neuroanatomical overlap and more widespread patterns of atrophy and tau deposition.

Akinetic Mutism and Cognitive‐Affective Syndrome caused by unilateral PICA infarction

AbstractBackgroundAkinetic mutism (AM) is characterized by sparse volitional motor and speech activation with reasonably preserved arousal and vigilance functions. Akinetic mutism, the most severe of these disorders, is most commonly associated with bilateral hemispheric pathology, although unilateral lesions may produce this condition as well.MethodCase: Our patient is a 42‐year‐old right handed man who presented to the emergency department with an acute onset of akinetic mutism. His family described him as a calm and intelligent individual with a good cultural knowledge level and without any evident cognitive abnormality before he suddenly experienced akinetic mutism. On examination, he was alert but produced no spontaneous speech and had only rare, spontaneous movement of his arm and leg. With repeated prompting, he followed single‐step commands.ResultMagnetic resonance imaging demonstrated an infarction in the distribution of the left posterior inferior cerebellar artery. During the course of 7 days, as the patient became more interactive, he demonstrated normal language function. As he became more communicative, cognitive impairment became apparent. Neuropsychological evaluation were performed after approximately 12 days after onset because of the impossibility of test administration during the acute phase. Impaired performances were evident on executive function testing with difficulties in planning, abstract reasoning, set‐shifting and perseveration. Furthermore, attention disorders and memory dysfunction were mild observed and were probably due to the poor ability of planning and organization. Language tests revealed mild deficits in the semantic sphere with paraphasia, anomia and circumlocutory expressions. During psychometric testing, the patient presented agitated and anxious behavior with affective air hunger and episodes of crying. Brain SPECT were performed after approximately 14 days after onset. Brain SPECT demonstrated hyporperfusion in Lt. cerebellar and frontal cortex.ConclusionThe syndrome of akinetic mutism is typically the result of bilateral hemispheric injury, usually involving the anterior cingulate gyri. Other locations for lesions producing akinetic mutism include the thalami, globus pallidus, internal capsule, and frontal white matter. We describe a man with akinetic mutism and cognitive impairment due to an ischemic stroke in the distribution of the left PICA.

A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8-/y mice

The creatine (Cr)-phosphocreatine shuttle is essential for ATP homeostasis. In humans, the absence of brain Cr causes significant intellectual disability, epilepsy, and language delay. Mutations of the creatine transporter (SLC6A8) are the most common cause of Cr deficiency. In rodents, Slc6a8 deletion causes deficits in spatial learning, novel object recognition (NOR), as well as in contextual and cued freezing. The mechanisms that underlie these cognitive deficits are not known. Due to the heterogeneous nature of the brain, it is important to determine which systems are affected by a loss of Cr. In this study, we generated mice lacking Slc6a8 in GABAergic neurons by crossing Slc6a8FL mice with Gad2-Cre mice. These Gad2-specific Slc6a8 knockout (cKO) mice, along with the ubiquitous Slc6a8 KO (Slc6a8-/y), Gad2-Cre+, and wild-type (WT) mice were tested in the Morris water maze, NOR, conditioned freezing, and the radial water maze. Similar to the Slc6a8-/y mice, cKO mice had reduced contextual and cued freezing compared with WT mice. The cKO mice had a mild spatial learning deficit during the reversal phase of the MWM, however they were not as pronounced as in Slc6a8-/y mice. In NOR, the Gad2-Cre mice spent less time with the novel object, similar to the reduced novel time in the cKO mice. There were no changes in radial water maze performance. Slc6a8 deletion in GABAergic neurons is sufficient to recapitulate the conditioned freezing deficits seen in Slc6a8-/y mice.

Vitamin B12 Deficiency and Hemolytic Anemia Presenting As Pseudo Thrombotic Microangiopathy: A Systematic Review

Introduction: Vitamin B12 deficiency is a common nutritional issue associated with mild anemia and neurological deficits. While rare, hemolytic anemia and low platelet count can be complications of this deficiency, often misdiagnosed as thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP). Pseudo TMA features can occur with B12 deficiency and can be effectively treated with vitamin B12 supplementation. In contrast, true TMA requires plasmapheresis. This systematic review aims to differentiate between pseudo TMA and TMA cases through an analysis of published case reports, providing valuable insights to avoid unnecessary treatments. Methods: We performed systematic review from Pubmed, Web of Science, and Scopus database. Twin independent reviewers (SY and BL) performed the screening using Covidence. Search keywords included “((hemolytic anemia) AND (vitamin B12 deficiency)) OR ((cobalamin deficiency) AND (hemolytic anemia)) Filters: English” for Pubmed, “(((ALL=(Cobalamin deficiency)) OR ALL=(vitamin B12 Deficiency))) AND ALL=(hemolytic anemia) Filter: English” for Web of Science and “( vitamin AND b12 AND deficiency OR cobalamin AND deficiency ) AND hemolytic AND anemia AND ( LIMIT-TO ( LANGUAGE , ”English“ ))” from Scopus. Only case reports in English with full-text availability and adult subjects were selected. Cases without final clinical outcome after treatment were excluded. After a comprehensive review, we identified 43 case reports and series with a total 53 patients that fulfilled our criteria. The details of selection process is illustrated in the prisma diagram (Figure 1). Results: The majority of cases involved males with low hemoglobin and platelet counts upon admission. Evidence of hemolysis was observed, indicated by increased lactate dehydrogenase (LDH), undetectable haptoglobin, and elevated or normal total and direct bilirubin levels. Peripheral blood films confirmed the presence of hemolytic anemia. Due to the co-occurrence of thrombocytopenia and hemolytic anemia, some cases were initially diagnosed as TTP, leading to the initiation of plasmapheresis. In 16 out of 53 reported case reports/series, patient received plasmapheresis. However, low reticulocyte index and normal ADAMTS 13 suggested an alternative diagnosis. Once ADAMTS 13 levels were normal, plasmapheresis was discontinued as TTP was ruled out. Diagnosis of B12 deficiency was confirmed by low B12 levels and elevated methylmalonic acid (MMA) levels. Leading cause for B12 deficiency were pernicious anemia in 28/53 cases, followed by dietary deficiency, and malabsorption due to surgery. Some patients also exhibiting concurrent iron deficiency anemia and folate deficiency. Treatment with subcutaneous B12 injections showed improvement in hemolysis as early as one week. Conclusion: Many cases of Vitamin B12 deficiency presenting with hemolytic anemia and thrombocytopenia are mistakenly diagnosed as TTP, leading to unnecessary and expensive plasmapheresis. Routine B12 level checks should be performed in all patients with hemolytic anemia, as B12 deficiency can be rapidly diagnosed and effectively treated, avoiding misdiagnoses and unnecessary interventions associated with TTP. The short turnover time for B12 levels (hours) compared to ADAMTS 13 activity (1-2 days) further supports the importance of routine B12 assessment in these patients.

Nigrostriatal tau pathology in parkinsonism and Parkinson's disease.

While Parkinson's disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the disease commonly consists of multiple pathologies, but it is unclear where these co-pathologies occur early in disease and whether they are responsible for the nigrostriatal degeneration. For the past number of years, we have been studying a well-characterized cohort of subjects with motor impairment that we have termed mild motor deficits. Motor deficits were determined on a modified and validated Unified Parkinson's Disease Rating Scale III but were insufficient in degree to diagnose Parkinson's disease. However, in our past studies, cases in this cohort had a selection bias, as both a clinical syndrome in between no motor deficits and Parkinson's disease, plus nigral Lewy pathology as defined post-mortem, were required for inclusion. Therefore, in the current study, we only based inclusion on the presence of a clinical phenotype with mild motor impairment insufficient to diagnose Parkinson's disease. Then, we divided this group further based upon whether or not subjects had a synucleinopathy in the nigrostriatal system. Here we demonstrate that loss of nigral dopaminergic neurons, loss of putamenal dopaminergic innervation and loss of the tyrosine hydroxylase-phenotype in the substantia nigra and putamen occur equally in mild motor deficit groups with and without nigral alpha-synuclein aggregates. Indeed, the common feature of these two groups is that both have similar degrees of AT8 positive phosphorylated tau, a pathology not seen in the nigrostriatal system of age-matched controls. These findings were confirmed with early (tau Ser208 phosphorylation) and late (tau Ser396/Ser404 phosphorylation) tau markers. This suggests that the initiation of nigrostriatal dopaminergic neurodegeneration occurs independently of alpha-synuclein aggregation and can be tau mediated.

Effects of full and deficit irrigation on the growth and quality of cool-season turfgrasses under subsurface drip irrigation

Irrigation is necessary in terms of achieving high-quality turfgrass. However, it is evident that more efficient and cost effective irrigation methods should be adapted for the sake of water conservation strategies since water consumption is high during turf irrigation. The objective of this study is to determine the effects of full and deficit irrigation with subsurface drip irrigation on growth and quality of perennial ryegrass (Lolium perenne L.) and tall fescue (Festuca arundinaceae Schreb) in a sub-humid climate of Turkey. Three irrigation treatments [I1 (full irrigation), I2 (mild water deficit, 75%), and I3 (moderate water deficit, 50%) were applied to the plants. Turf color and quality of each plot were rated visually, and clipping yields were collected. The amount of irrigation applied varied between 457.3 - 833.9 mm and 356.7 - 710.1 mm and seasonal crop evapotranspiration (ETa) values ranged from 578.4 to 1053.0 mm for tall fescue and 551.2 to 1044.0 mm for perennial ryegrass in 2018 and 2019, respectively. Among the species, tall fescue showed higher visual color, quality ratings and clipping yields. In cases where it does not matter for one or two weeks to be below the acceptable quality (<6) minimum annual irrigation amounts required to maintain quality was 689.1 mm for perennial ryegrass and 578.4 for tall fescue. The results have suggested that acceptable visual color and quality are sustainable in the tall fescue with mild water deficit application in regions where irrigation water is limited in sub-humid climates. Studies on water-saving strategies to turfgrass in regions where the climates varies from year to year are lacking in literature.

Photosynthetic characteristics, yield and quality of sunflower response to deficit irrigation in a cold and arid environment.

In arid regions, deficit irrigation stands as an efficacious strategy for augmenting agricultural water conservation and fostering sustainable crop production. The Hexi Oasis, an irrigation zone situated in Northwest China, serves as a pivotal area to produce grain and cash crops. Nonetheless, due to the predominant conditions of low rainfall and high evaporation, the scarcity of irrigation water has emerged as a critical constraint affecting crop growth and yield in the area. In order to evaluate the effects of deficit irrigation on photosynthetic characteristics, yield, quality, and water use efficiency of sunflower, a two-year field experiment with under-mulched drip irrigation was conducted in the cold and arid environment of the Hexi Oasis region. Water deficits were implemented at sunflower seedling and maturity and consisted of three deficit levels: mild deficit (65-75% field capacity, FC), moderate deficit (55-65% FC), and severe deficit (45-55% FC). A total of six combined water deficit treatments were applied, using full irrigation (75-85% FC) throughout the entire crop-growing season as the control (CK). The results illustrated that water deficit engendered a decrease in leaf net photosynthetic rate, transpiration rate, and stomatal conductance of sunflower compared to CK, with the decrease becoming significant with the water deficit increasing. A mild water deficit, both at the seedling and maturity phases, precipitated a significant enhancement (p< 0.05) in leaf water use efficiency. Under mild water deficit, stomatal limitation emerged as the predominant factor inducing a reduction in the photosynthetic capacity of sunflower leaves, while as the water deficit escalated, non-stomatal limitation progressively assumed dominance. Moreover, a mild/moderate water deficit at seedling and a mild water deficit at maturity (WD1 and WD3) significantly improved sunflower seed quality under consistent yield conditions and significantly increased irrigation water use efficiency, with an average increase of 15.3% and 18.5% over the two years, respectively. Evaluations utilizing principal component analysis and membership function methods revealed that WD1 attained the highest comprehensive score. Consequently, a mild water deficit at both seedling and maturity (WD1) is advocated as the optimal deficit irrigation strategy for sunflower production within the cold and arid environment of Northwest China.

Meta-Analysis of the Effect of Subsurface Irrigation on Crop Yield and Water Productivity

Problems such as population growth and climate change have led to a reduction in the use of water for irrigated agriculture, constraining the growth of crops. Subsurface irrigation, as a widely used and efficient water-saving irrigation technology, varies in its effect on increasing yields and saving water under different environmental, management, and other conditions. To investigate the effects of subsurface irrigation on yield, water productivity (WP), and irrigation water productivity (IWP) of three typical crops (wheat, maize, and cotton), this paper conducted a meta-analysis of 528 pairs of studies from 64 papers worldwide to quantify the response of crop yield, WP, and IWP to subsurface irrigation. Overall, the yield, WP and IWP increased by 5.96%, 21.62%, and 27.72%, respectively, with subsurface irrigation compared with surface irrigation. Compared with other conditions, the greatest rate of change was observed at around 200–500 m above sea level, 10–15 °C average annual temperature, 1.45–1.55 g/cm3 soil bulk density, alkaline soil, and when the crops were planted with equal row spacing. Meanwhile, the amount of irrigation water, as well as the subsurface pipeline arrangement and burial depth, had significant effects on crop yield, WP, and IWP. The maximum increase in crop yield, WP, and IWP was favored when the irrigation volume of the subsurface irrigation was reduced by 50–100% compared with surface irrigation or when both had the same volume of irrigation but a mild water deficit. In addition, the yield, WP, and IWP were also affected by fertilization factors. The recommended fertilizer application rates were ≤90 kg P ha–1 (phosphorus) and &lt;150 kg N ha–1 (nitrogen). Compared with surface irrigation, subsurface irrigation showed the greatest yield increase when fertilizer was applied in a one-time application, and the WP and IWP increased significantly when the number of fertilizer applications was &lt;3.

73 Identification of 24-Month Cognitive Trajectories Among Clinical High Risk for Psychosis (CHR-P) Using Latent Class Mixture Modeling

Objective:Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.Participants and Methods:Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning &amp; problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (&gt;5%).Results:A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).Conclusions:Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Association of early surgery and absence of ataxia with full recovery after spinal intramedullary ependymoma resection.

Spinal intramedullary ependymomas (IEs) represent a well-defined tumor entity usually warranting resection. Factors that determine full long-term neurological recovery after resection are seldomly reported on in larger clinical series. In this study, the authors aimed to highlight the neurological outcome of patients with IEs after resection, with a focus on full neurological recovery, and to explore possible risk factors for the absence of neurological amelioration to an optimal function after surgical treatment. A single-center retrospective analysis of all patients undergoing surgery for IEs between 2007 and 2021 was performed. Data collection included patient demographics, symptoms, clinical findings, histopathological diagnosis, surgical procedures, complications, and neurological outcome. Patients harboring a favorable outcome (modified McCormick Scale [mMS] grade of I) were compared with patients with a less favorable outcome (mMS grade ≥ II) at the final follow-up. In total, 72 patients with a histologically diagnosed IE were included. IEs in those patients (41 males, 31 females; median age 51 [IQR 40-59] years) mostly occurred in the cervical (n = 40, 56%) or thoracic (n = 23, 32%) spine. Upon admission, motor deficits or gait deficits (mMS grade ≥ II) were present in 29 patients (40%), with a median mMS grade of II (IQR I-II). Gross-total resection was achieved in 60 patients (90%), and the rate of surgical complications was 7%. Histopathologically, 67 tumors (93%) were classified as WHO grade 2 ependymomas, 3 (4%) as WHO grade 1 subependymomas, and 2 (3%) as WHO grade 3 anaplastic ependymomas. After a mean follow-up of 863 ± 479 days, 37 patients (51%) had a fully preserved neurological function and 62 patients (86%) demonstrated an mMS grade of I or II. Comparison of favorable with unfavorable outcomes revealed an association of early surgery (within a year after symptom onset), the absence of ataxia or gait disorders, and a low mMS grade with full neurological recovery at the final follow-up. A subgroup of patients (n = 15, 21%) had nonresolving deterioration at the final follow-up, with no significant differences in relevant variables compared with the rest of the cohort. The data presented solidify the role of early surgery in the management of spinal IEs, especially in patients with mild neurological deficits. Furthermore, the presence of gait disturbance or ataxia confers a higher risk of incomplete long-term recovery after spinal ependymoma resection. Because a distinct subgroup of patients had nonresolving deterioration, even when presenting with an uneventful history, further analyses into this subgroup of patients are required.

Disease course and psychosocial outcome for children and adolescents with anti-N-methyl-D-aspartate receptor encephalitis.

Explore psychosocial outcome and impact of persisting deficits on quality of life (QoL) and global functioning after anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) in children and adolescents. Four female patients (age 7-16y) and their caregivers participated in the study. Information was collected from the medical records and the caregivers via a questionnaire. Both the patients and their caregivers were interviewed by means of the structured clinical interview for DSM-5 disorders, junior version (SCID-5 junior). CGAS and mRS scores were defined and the Pediatric Quality of Life Inventory (PedsQL) was used to assess quality of life of patients and caregivers. After the acute phase of the disease patients go through a post-acute phase in which several persisting physical, cognitive and psychiatric symptoms gradually resolve during the following months to a year. In long-term follow up these symptoms partly resolved, but deficits persisted on several domains. Psychiatric symptoms, fatigue and mild cognitive deficits were present in three out of four patients at current assessment. In three patients their academic trajectory was altered. These deficits can have an impact on the quality of life and the global functioning of the patients and caregivers.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents. Awake male and female Sprague Dawley rats (postnatal Day 35) received 140 closed-head impacts over the course of a week. Impacted and sham-impacted animals were restrained in a plastic cone, and unrestrained control animals were included to account for effects of restraint and normal development. Animals (n = 43) underwent repeated diffusion tensor imaging prior to and over 1 month following the final impact. A separate cohort (n = 53) was assessed behaviourally for fine motor control, emotional-affective behaviour and memory at acute and chronic time points. Histological and immunohistochemical analyses, which were exploratory in nature due to smaller sample sizes, were completed at 1 month following the final impact. All animals tolerated the protocol with no overt changes in behaviour or stigmata of traumatic brain injury, such as alteration of consciousness, intracranial haemorrhage or skull fracture. We detected longitudinal, sex-dependent diffusion tensor imaging changes (fractional anisotropy and axial diffusivity decline) in corpus callosum and external capsule of repetitive subconcussive head impact animals, which diverged from both sham and control. Compared to sham animals, repetitive subconcussive head impact animals exhibited acute but transient mild motor deficits. Repetitive subconcussive head impact animals also exhibited chronic anxiety and spatial memory impairment that differed from the control animals, but these effects were not different from those seen in the sham condition. We observed trends in the data for thinning of the corpus callosum as well as regions with elevated Iba-1 in the corpus callosum and cerebral white matter among repetitive subconcussive head impact animals. While replication with larger study samples is needed, our findings suggest that subconcussive head impacts cause microstructural tissue changes in the developing rat brain, which are detectable with diffusion tensor imaging, with suggestion of correlates in tissue pathology and behaviour. The results point to potential mechanisms underpinning consequences of subconcussive head impacts that have been described in humans. The congruence of our imaging findings with human subconcussive head impacts suggests that neuroimaging could serve as a translational bridge to advance study of injury mechanisms and development of interventions.

92 Teleneuropsychological Evaluation of Bariatric Surgery Candidates: Cognitive Profiles and Recommendations for Future Practice

Objective:Vascular complications, including elevated body mass index (BMI), are known risk factors for cognitive impairment. Obtaining a cognitive baseline is commonplace in pre-surgical protocols, including for Parkinson’s disease and epilepsy. Currently, routine evaluations for bariatric surgery candidates do not include neuropsychological assessment. This setting provides a unique opportunity to identify cognitive profiles of younger individuals at risk for cognitive impairment. Here, we argue for the standard implementation of a brief, online cognitive battery via telemedicine, to enhance existing protocols of bariatric pre-surgical evaluations.Participants and Methods:Nineteen bariatric surgery candidates were referred to a private neuropsychological assessment practice for pre-surgical cognitive/psychological evaluation. Assessments were conducted by a neuropsychologist and a psychology graduate student, via remote video conferencing, between April 2020 and June 2022. Candidates completed a clinical interview, intake form, and the Behavior Rating Inventory of Executive Function for Adults (BRIEF-A), and were administered a battery of cognitive measures: Wechsler Test of Adult Reading (WTAR), Hopkins Verbal Learning Test-Revised (HVLT-R); and select subtests from the TestMyBrain Digital Neuropsychology Toolkit: Trail Making Tests A and B (TMT-A/B), Matrix Reasoning (MR), Digit Span Forward and Backward (DSF, DSB), Gradual Onset Continuous Performance Test (CPT), and Simple and Choice Reaction Time (SRT, CRT). Descriptive statistics were conducted to analyze sample demographics. Raw scores on cognitive measures were converted to z-scores and averaged across the sample.Results:The average age at evaluation was 38.2 (9.6) years and average pre-surgical BMI was 46.6k/m2 (9.3), indicating morbid obesity (BMI&gt;40k/ m2). Ten (52.6%) candidates identified as female, 10 (52.6%) identified as White, 8 (42.1%) had 12 years of education or less, 4 (21.1%) were unemployed, and 9 (47.4%) had comorbid psychiatric diagnoses. BRIEF-A sub-scales were within the average range (T’s= 47.9 - 52.9, SD’s [10.1 - 12.8]). Estimated premorbid IQ was average at 102.7 (11.4). Neuropsychological data revealed group performance within the average range on DSF and DSB (z’s= 0.00), TMT-A (z= -0.16), MR (z= -0.53), CPT (z= -0.39), and HVLT-R False Positives (z= 0.05) and Recognition Discriminability (z= -0.44). SRT (z= -0.70), CRT Accuracy (z= -1.37), TMT-B (z= -0.79), HVLT-R Total Recall and Percent Retained (z’s= -0.88), and Delayed Recall and True Positives (z’s= -1.27) were low average.Conclusions:In this sample of pre-surgical bariatric candidates with average intelligence, baseline evaluations revealed mild deficits in reaction time accuracy, visual motoric set-shifting, and verbal learning/memory. These deficits may be the result of microvascular changes in the brain secondary to physical compromise. Results provide additional insight into potential early-onset executive dysfunction, psychomotor slowing, and verbal learning/memory difficulties. In addition to these relative areas of neuropsychological weakness, candidates demonstrated relative strengths in attention, working memory, and visuospatial functioning. These insights provide pre-surgical evaluators with additional information to tailor recommendations and treatment approaches that foster surgical success. With a remote, concise, easy-to-administer battery of tests, routine neuropsychological assessment for bariatric surgery candidates is both a feasible and a useful tool for identifying areas of cognitive strengths and weaknesses. Documenting a patients’ cognitive baseline can assist with monitoring long-term vascular risk-factors and potential cognitive impairment.

Effective Treatments for the Successful Establishment of Milkweed (Calotropis procera L.) under Water Deficit

The application of superabsorbents to soils and seed coatings is a pre-sowing seed treatment method that is commonly used to improve early vigor and establish stability and uniformity under water deficit conditions. To evaluate the interaction of seed coating and superabsorbent on Calotropisprocera L. (milkweed) under water deficit conditions, a greenhouse experiment was conducted. The experiment was conducted with four coating material levels (non-coated seeds and seeds coated with peat moss, vermicompost, and canola residue), four growth medium levels (soil, sand + soil, soil + 2 g superabsorbent, and soil + 4 g superabsorbent), and three field capacity regimes (25, 50%, and 100%) in a completely randomized design factorial arrangement with four replications. Reducing the field capacity from 100 to 25% led to decreased growth (shoot and root dry weights and leaf area) and chlorophyll content. The activities of SOD, CAT, APX antioxidant enzymes, and proline increased under drought stress. The use of superabsorbent polymers in growth media enhanced growth indices and chlorophyll content and decreased the activity of antioxidant enzymes and proline under water deficit conditions. The highest chlorophyll and growth indices were observed when 4 g of superabsorbent was added to the growth medium under drought stress. The application of 4 g of superabsorbent to the growth medium reduced the activity of antioxidant enzymes and proline. The use of seed coatings improved the growth indices, antioxidant enzyme activity, and chlorophyll content under drought stress. The most adaptive morphological and physiological responses to water stress were observed in the vermicompost-coated seeds. The vermicompost coating containing a superabsorbent polymer (4 g/kg soil) proved to be the best for establishing milkweed under mild (50% FC) and severe water deficits (25% FC).

The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): Protocol for a Pragmatic, Stepped Wedge, Cluster Randomized Controlled Trial

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications. Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events. Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

Metabolic and Transcriptomic Approaches of Chitosan and Water Stress on Polyphenolic and Terpenoid Components and Gene Expression in Salvia abrotanoides (Karl.) and S. yangii.

In this research, a HPLC analysis, along with transcriptomics tools, was applied to evaluate chitosan and water stress for the prediction of phenolic flavonoids patterns and terpenoid components accumulation in Salvia abrotanoides Karel and S. yangii. The results indicated that the tanshinone contents under drought stress conditions increased 4.2-fold with increasing drought stress intensity in both species. The rosmarinic acid content in the leaves varied from 0.038 to 11.43 mg/g DW. In addition, the flavonoid content was increased (1.8 and 1.4-fold) under mild water deficit conditions with a moderate concentration of chitosan (100 mg L-1). The application of foliar chitosan at 100 and 200 mg L-1 under well-watered and mild stress conditions led to increases in hydroxyl cryptotanshinone (OH-CT) and cryptotanshinone (CT) contents as the major terpenoid components in both species. The expressions of the studied genes (DXS2, HMGR, KSL, 4CL, and TAT) were also noticeably induced by water deficit and variably modulated by the treatment with chitosan. According to our findings, both the drought stress and the application of foliar chitosan altered the expression levels of certain genes. Specifically, we observed changes in the expression levels of DXS and HMGR, which are upstream genes in the MEP and MVA pathways, respectively. Additionally, the expression level of KSL, a downstream gene involved in diterpenoid synthesis, was also affected. Finally, the present investigation confirmed that chitosan treatments and water stress were affected in both the methylerythritol phosphate pathway (MEP) and mevalonate (MVA) pathways, but their commitment to the production of other isoprenoids has to be considered and discussed.

Prefrontal event-related potential markers in association with mild cognitive impairment.

Alzheimer's disease (AD) is among the leading contributors of dementia globally with approximately 60-70% of its cases. Current research is focused on the mild cognitive impairment (MCI), which is associated with cognitive decline but does not disrupt routine activities. Event-related potential (ERP) research is essential in screening patients with MCI. Low-density channel electroencephalography (EEG) is frequently used due to its convenience, portability, and affordability, making it suitable for resource-constrained environments. Despite extensive research on neural biomarkers for cognitive impairment, there is a considerable gap in understanding the effects on early stages of cognitive processes, particularly when combining physiological and cognitive markers using portable devices. The present study aimed to examine cognitive shortfalls and behavioral changes in patients with MCI using prefrontal selective attention ERP recorded from a prefrontal two-channel EEG device. We assessed cognitive decline using the Mini-Mental State Examination (MMSE) and the Seoul Neuropsychological Screening Battery (SNSB). We administered auditory selective attention tasks to 598 elderly participants, including those with MCI (160) and cognitively normal (CN) individuals (407). We conducted statistical analyses such as independent t-tests, Pearson's correlations, and univariate and multiple logistic regression analyses to assess group differences and associations between neuropsychological tests, ERP measures, behavioral measures, and MCI prevalence. Our findings revealed that patients with MCI demonstrated slower information-processing abilities, and exhibited poorer task execution, characterized by reduced accuracy, increased errors, and higher variability in response time, compared to CN adults. Multiple logistic regression analyses confirmed the association between some ERP and behavioral measures with MCI prevalence, independent of demographic and neuropsychological factors. A relationship was observed between neuropsychological scores, ERP, and behavioral measures. The slower information processing abilities, and poor task execution in the MCI group compared to the CN individuals suggests flawed neurological changes and reduced attentional maintenance during cognitive processing, respectively. Hence, the utilization of portable EEG devices to capture prefrontal selective attention ERPs, in combination with behavioral assessments, holds promise for the identification of mild cognitive deficits and neural alterations in individuals with MCI. This approach could potentially augment the traditional neuropsychological tests during clinical screening for MCI.

The Nociceptin/Orphanin FQ peptide receptor antagonist, SB-612111, improves cerebral blood flow in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) affects more than 2.5 million people in the U.S. each year and is the leading cause of death and disability in children and adults ages 1 to 44. Approximately 90% of TBI cases are classified as mild but may still lead to acute detrimental effects such as impaired cerebral blood flow (CBF) that result in prolonged impacts on brain function and quality of life in up to 15% of patients. We previously reported that nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonism reversed mild blast TBI-induced vestibulomotor deficits and prevented hypoxia. To explore mechanisms by which the NOP receptor-N/OFQ pathway modulates hypoxia and other TBI sequelae, the ability of the NOP antagonist, SB-612111 (SB), to reverse TBI-induced CBF and associated injury marker changes were tested in this study. Male Wistar rats randomly received sham craniotomy or craniotomy + TBI via controlled cortical impact. Injury severity was assessed after 1h (modified neurological severity score (mNSS). Changes in CBF were assessed 2h post-injury above the exposed cortex using laser speckle contrast imaging in response to the direct application of increasing concentrations of vehicle or SB (1, 10, and 100µM) to the brain surface. TBI increased mNSS scores compared to baseline and confirmed mild TBI (mTBI) severity. CBF was significantly impaired on the ipsilateral side of the brain following mTBI, compared to contralateral side and to sham rats. SB dose-dependently improved CBF on the ipsilateral side after mTBI compared to SB effects on the respective ipsilateral side of sham rats but had no effect on contralateral CBF or in uninjured rats. N/OFQ levels increased in the cerebral spinal fluid (CSF) following mTBI, which correlated with the percent decrease in ipsilateral CBF. TBI also activated ERK and cofilin within 3h post-TBI; ERK activation correlated with increased CSF N/OFQ. In conclusion, this study reveals a significant contribution of the N/OFQ-NOP receptor system to TBI-induced dysregulation of cerebral vasculature and suggests that the NOP receptor should be considered as a potential therapeutic target for TBI.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases in the Motor Cortex.

To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm 3 -12.18 cm 3 , mean 0.74 cm 3 ) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) ( P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.

Clock Drawing Test: Types of Errors and Accuracy in Early Cognitive Screening.

Clock Drawing Test (CDT) is a commonly used screening tool for cognitive disorders, known for its ease of administration and scoring. Despite frequent use by clinicians, CDT is criticized for its poor predictive value in mild cases of impairment. To evaluate CDT as a screening tool for early stage of cognitive impairment in biomarker-verified Alzheimer's disease (AD) and depressive disorder (DD). We analyzed CDT of 172 patients with verified AD, 70 patients with DD, in whom neurodegenerative disorder was excluded using cerebrospinal fluid biomarkers, and 58 healthy older adults. CDT was scored using the semi-quantitative (Shulman) and itemized criteria (adapted from Mendez). Logistic regression showed that for both DD and AD patients with high Mini-Mental State Examination (MMSE) scores (27 and above) the significant predicting variable is uneven number spacing. As MMSE deteriorates (24-26 points), an additional error of setting clock hands is predictive of the disease. In the low MMSE condition, CDT showed an acceptable discrimination for AD (AUC itemized 0.740, Shulman 0.741) and DD (AUC itemized 0.827, Shulman 0.739) using both scoring methods. In the high MMSE condition, discrimination rates were acceptable using itemized scoring but poor using Shulman scoring for both AD (AUC itemized 0.707, Shulman 0.677) and DD (AUC itemized 0.755, Shulman 0.667) groups. Ideally, modern diagnostic process should take place before the cognitive performance drops beneath the healthy range. This makes CDT of little use when screening patients with very mild cognitive deficits.