Normative Mean Research Articles

사회변화와 사회적 기본권

From the first constitution in 1948, at least normatively, our Constitution not only guaranteed freedom, but also clearly declared that individual social circumstances should be considered and socioeconomic integration should be realized, and this was embodied through various social basic rights regulations. However, despite these normative circumstances, social basic rights did not have constitutional authority until the late 1980s. Constitutional reality and the unique realization structure of social basic rights worked here.
 Since the establishment of the Constitutional Court under the Constitution in 1987, the constitutional tasks of the welfare state have been discussed in earnest, laying the foundation for social basic rights to become a constitutional reality. Social basic rights are normatively open norms in their content, goals, and methods of realization, but their realization tends to be subordinated to external decisions about realistic situations. Social basic rights can be activated under a democracy where the possibility of dynamic and pluralistic decision-making is open, but on the other hand, it is also a factor that can deepen its instability. Among these tensions is the Constitutional Court. Although the Constitutional Court has contributed to the recognition and functioning of the Constitution as a norm with universal effect since 1987, it is inevitable to be critical of how much the Constitution and Constitutional Court have contributed to social integration, guaranteeing conditions for freedom and opportunities for social participation to all citizens. Until now, due to normative or practical obstacles, the Constitutional Court has repeated most of its passive judgments in judicial review of social basic rights. However, at a time when the scope of the constitutional task for the welfare state extends beyond welfare measures for marginalized human groups to the issue of intergenerational equity for sustainability, the constitutional trial can no longer settle for passive judgment.
 In order for constitutional values to play an important driving role in forming a social security legislative system for the realization of social basic rights in the future, the Constitutional Court should define the normative meaning of social basic rights and seek active guarantees for social basic rights.

CEREBROSPINAL FLUID MARKERS OF ALZHEIMER’S-RELATED PATHOLOGY RELATE TO AMCI AMONG PEOPLE WITH HIV

Abstract Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). To investigate the utility of CSF AD pathology markers in differentiating aMCI from HAND, we assessed how these markers differentially relate to aMCI versus HAND status among PWH. Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium who completed a neurocognitive test battery assessing seven cognitive domains and had CSF biomarker data for Aβ42, p-tau181, p-tau181/Aβ42 ratio, Neopterin and NfL. aMCI was defined as impairment (<1.0 SD below normative mean) on ≥2 memory outcomes among learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in ≥2 cognitive domains. Separate linear regression models adjusting for demographic and HIV-related characteristics were used to examine how individual biomarkers relate to diagnostic status. Fifty-eight percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. CSF p-tau/Aβ42 ratio levels were higher (indicative of greater pathology) in PWH with versus without aMCI (β=.363, p=.001), but did not differ by HAND status. No other AD biomarker significantly differed by group status. Results indicate that the CSF p-tau181/Aβ42 ratio relates specifically to an aMCI-like profile among PWH, and, thus, may contribute to disentangling aMCI from HAND and informing the need for further diagnostic procedures.

ASSESSING MOTOR FUNCTION IN FRAIL OLDER ADULTS IN THEIR HOME SETTING: CHALLENGES AND OPPORTUNITIES

Abstract Motor function is essential for older adults to perform daily activities and remain in their home as they age. Mounting evidence suggests that physical activity (PA) helps maintain motor function in older adults. However, few evidence-based PA programs exist for home-bound older adults who have difficulties walking or standing. They are typically excluded from randomized controlled trials (RCT). Evidence is difficult to establish, because of the lack of instruments and protocols for assessing motor function safely and effectively in this population. The goal of this paper is to present challenges and opportunities that we encountered in assessing motor function in 119 participants of the Pro-Home study right before the COVID-19 pandemic. As expected, participants had significant physical limitations. One third of the participants did not feel safe doing balance tests or chair stand test included in the Short Physical Performance Battery. Of those who did the balance tests, two thirds had to use compensatory movement or hold on to an object to maintain balance. Interestingly, 30% of participants had cognitive impairment as defined by 1.5 Standard Deviation below the normative mean measured by NIH Toolbox Cognition Battery, although they passed a six-item cognition screener to be eligible for Pro-Home. The challenges of assessing frail older adults have led to opportunities to adapt assessment protocols. We made instructions clear and easy-to-follow and developed a new measure appropriate and safe for our target, frail older participants. Additional safety measures are needed to facilitate motor function assessments in frail older adults.

Voice Recognition in the era of Virtual Reality: Disruption of Normative Social Meaning Making

The teaching and working world has been disrupted by developments known as the 4th Industrial Revolution. As we grappled with the Covid-19 epidemic the world saw massive disruptions in how and where we work, teach, learn and socialize. As moves to continue the social via virtual platforms increased as a result of Covid-19 restrictions we saw disruptions in everyday social meaning making. This article via reflections from personal observation and conversations with colleagues engages with the idea of voice recognition as an important social cue in virtual interactions. The article shows how taken for granted social markers of engagement can be rendered useless in context were the only connector to the people you are interacting with is their voice. The article challenges us to engage with the following questions: What impacts does the move to virtuality have on social engagements that allow us to humanize each other? What can we do to maintain the important social cues important for meaning making in context of teaching, counseling, consultation as we see many of these roles move to the virtual space?

Cerebral blood flow and neurocognition in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis.

Aortic valve stenosis (AS) results in higher systolic pressure to overcome resistance from the stenotic valve, leading to heart failure and decline in cardiac output. There has been no assessment of cerebral blood flow (CBF) association with neurocognition in AS or the effects of valve replacement. The goal was to determine if AS is associated with altered cerebral haemodynamics and impaired neurocognition, and whether transcatheter aortic valve replacement (TAVR) improves haemodynamics and cognition. In 42 patients with planned TAVR, transcranial Doppler (TCD) assessed bilateral middle cerebral artery (MCA) mean flow velocities (MFVs); abnormality was <34.45 cm/s. The neurocognitive battery assessed memory, language, attention, visual-spatial skills, and executive function, yielding a composite Z-score. Impairment was <1.5 SDs below the normative mean. The mean age was 78 years, 59% Male, and the mean valve gradient was 46.87 mm/Hg. Mean follow-up was 36 days post-TAVR (range 27-55). Pre-TAVR, the mean MFV was 42.36 cm/s (SD = 10.17), and the mean cognitive Z-score was -0.22 SDs (range -1.99 to 1.08) below the normative mean. Among the 34 patients who returned after TAVR, the MFV was 41.59 cm/s (SD = 10.42), not different from baseline (P = 0.66, 2.28-3.67). Post-TAVR, average Z-scores were 0.17 SDs above the normative mean, not meeting the pre-specified threshold for a clinically significant 0.5 SD change. Among patients with severe AS, there was little impairment of MFV on TCD and no correlation with cognition. Transcatheter aortic valve replacement did not affect MFV or cognition. Assumptions about diminished CBF and improvement after TAVR were not supported.

Subtle cognitive difficulties increase risk of neurodegeneration, incident mild cognitive impairment, and dementia in older women.

AbstractBackgroundIdentifying individuals with preclinical Alzheimer’s disease and related disorders (ADRD) is important for prevention and eventual treatment. Here we aimed to integrate overall test performance with episodic memory process scores in a cohort of older women to identify those with subtle cognitive difficulties (SCD; e.g., individuals with the earliest declines in cognitive ability preceding a diagnosis of mild cognitive impairment (MCI) or dementia) and determine subsequent risk of MCI, dementia, and neuroimaging indices of neurodegeneration.MethodParticipants included 2,186 community‐dwelling older women without MCI or dementia (Mage = 73.4±3.8 years) who completed a comprehensive neuropsychological assessment as part of the Women’s Health Initiative Study of Cognitive Aging (WHISCA: 1999‐2000). Women were assessed annually for MCI and dementia until 2021, and 1,024 women underwent structural magnetic resonance imaging (sMRI) of the brain in 2005‐6. Women were classified as cognitively normal (CN), early SCD (e‐SCD; two episodic memory process scores 1 SD below normative means or one process score and one performance score 1 SD below normative means), or late SCD (l‐SCD; two overall performance scores 1 SD below normative means) at WHISCA baseline using validated criteria from the Alzheimer’s Disease Neuroimaging Cohort (Thomas et al., 2018 Journal of Alzheimer’s Disease). We used Cox proportional hazards to examine associations between SCD status and risk of developing MCI/dementia. Linear regressions were used to examine associations between SCD status and MRI indices of AD‐related neurodegeneration, global cerebrovascular damage, and brain volumes of structures that make up the medial temporal lobe. All associations were adjusted for sociodemographic, lifestyle, and clinical characteristics.ResultWomen with e‐SCD and l‐SCD were 1.58 (p&lt;0.001) and 3.01 (p&lt;0.001) times as likely to develop MCI/dementia compared to CN women, respectively (Figure 1). Women with l‐SCD (β = 0.20; p&lt;0.001) had more AD‐related neurodegeneration compared to CN women (Table 1). Women with e‐SCD had marginally significantly greater AD‐related neurodegeneration (β = 0.14; p = 0.073) and had smaller volumes in the entorhinal cortex (β = ‐0.22; p = 0.009) compared to CN women.ConclusionOur study demonstrates the usefulness of the SCD criteria for the early identification of cognitively normal women who are at increased risk of MCI, dementia, and neurodegeneration.

Neurodevelopmental outcome at 5.5 years in Dutch preterm infants born at 24–26 weeks’ gestational age: the EPI-DAF study

ObjectiveAfter lowering the Dutch threshold for active treatment from 25 to 24 completed weeks’ gestation, survival to discharge increased by 10% in extremely preterm live born infants. Now that this...

1325. Neurodevelopmental outcomes in preschoolers following viral meningitis is Canterbury, New Zealand

Abstract Background Most childhood meningitis nowadays is caused by viruses in countries with widespread use of conjugate vaccines. There is limited knowledge about outcomes following childhood viral meningitis, necessary to inform clinical guidelines. Methods Children aged 19-42 months in Canterbury New Zealand, who had enterovirus (EV) or human parechovirus (HPEV) meningitis as infants were included. Clinical data was collected. Comprehensive neurodevelopmental assessments were completed using the Bayley Scale for Infant Development (BSID) Third Edition. Mean composite and scaled scores, and proportion below cutoff were assessed in each domain. Normative mean composite scores for any domain is 100. Expected scaled score range is 8-12. Mean scores between EV and HPEV meningitis were compared by t-tests, with P&amp;lt; 0.05 considered significant. Results BSID assessments were completed for 33 children (55% male) of mean age 31 months, from 2019-22, including 23 with EV and 10 with HPEV meningitis. There were 24 children of NZ European, 4 Māori, 4 Asian, and 1 Middle Eastern ethnicity. Mean age at diagnosis was 43 days, and mean length of admission was 2.79 days (CI 1.74-3.15). Of 33 children, 32 (97%) received intravenous or intramuscular antibiotics, 6 (18%) received a fluid bolus on arrival at hospital, and 9 (27%) required high dependency or intensive care. Following viral meningitis, parents reported developmental speech concerns in 6 children, and delayed motor milestones in 1 child. There was no reported sensorineural hearing loss. BSID mean composite scores were in expected range for cognition 102 (CI 98-106), language 96 (93-100) and motor 102 (98-106) domains. Mean scaled scores were in expected range for receptive language 9 (9-10), expressive language 9 (9-10), fine motor 11 (11-12) and gross motor 9 (9-10) domains. Overall, 12/33 (36%) children had below expected scores in one area of development including cognition (2/33; 6%), receptive language (6/33; 18%), expressive language (5/33; 15%), and gross motor (6/33; 18%). There were no significant differences between BSID scores in EV and HPEV meningitis. Conclusion Following viral meningitis, 36% percent of preschool children had findings below expected in at least one developmental domain, suggesting targeted follow-up should be considered. Disclosures Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support

Abstract 13952: Neurodevelopmental Outcomes in Early Adolescence: The Pediatric Heart Network’s Single Ventricle Reconstruction Trial

Introduction: Neurodevelopmental (ND) and functional impairments for survivors of palliated hypoplastic left heart syndrome (HLHS) are among the most consequential morbidities, resulting in an increased risk of poor school performance and lower reported quality of life. Longitudinal follow-up of those enrolled in the Single Ventricle Reconstruction (SVR) III study provides opportunity to measure important outcomes such as ND, and understand associated risk factors. Goals/Aims: Describe and identify predictors of ND outcomes at 10-12 years of age in participants enrolled in SVR. Methods: Transplant-free survivors from the SVR III trial were invited to complete in-person ND assessments, including the Wechsler Intelligence Scale for Children-V, Wechsler Individual Achievement Test-III, and the Behavior Rating Inventory of Executive Function (BRIEF). Descriptive and regression analyses were performed. Results: Of the 237 enrolled in SVR III, 200 (84%) received a ND assessment. Participants who did vs did not undergo assessment were more likely to be male (63% vs 51%), white (87% vs 76%) and have a higher Child Opportunity Index (61 ±26 vs 46 ±39). Mean Full Scale IQ for the cohort was almost 1 standard deviation (SD) below the normative mean (88 ±18), with 39% &gt;1 and 15% &gt;2 SD below the normative mean. Similar patterns were seen for Reading (38% &gt;1 SD and 16% &gt; 2SD) and Math Composites (38% &gt;1 SD, 19% &gt; 2SD). Executive functions measured with the BRIEF were similarly affected, with 25% to 45% of individuals showing clinically significant (T score &gt;65) Plan/Organization problems on parent and teacher forms, respectively. Measures of socioeconomic status, number of complications, and requirement for a gastrostomy-tube were all independent predictors for multiple ND outcomes. Conclusions: In early adolescence, transplant-free survivors of surgical palliation for HLHS show clinically significant ND concerns across multiple domains of functioning. The distribution of outcomes is broad. Our findings support the American Heart Association recommendations for screening and evaluation in middle school to inform interventions that promote academic success and quality of life.

57 CSF Markers of AD-Related Pathology Relate to aMCI among People with HIV

Objective:Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levelsParticipants and Methods:Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (&lt;1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (&lt;1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.Results:58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.Conclusions:Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.

2 Cross Cultural Application of the International Classification of Cognitive Disorders in Epilepsy (IC CoDE) Cognitive Phenotypes in People with Temporal Lobe Epilepsy in India

Objective:To apply the new IC-CoDE cognitive diagnostic taxonomy (Norman et al., 2020) to a large cohort of people with temporal lobe epilepsy (TLE) in India. The IC-CoDE taxonomy of cognitive diagnoses for 1,409 Englishspeaking adults with TLE from seven epilepsy centres in the U.S. has been published (McDonald et al., 2022). Initial results suggest that the IC-CoDE produces stable cognitive phenotypes across centres; however, its international applicability, including the suggested impairment cut-off needs to be considered across cultures and languages to avoid misclassification. The aim of this study was to apply the IC-CoDE to a population, outside of the U.S., diverse in language representation (i.e., bi/multi-lingual), assessment tools, normative data, and educational and cultural backgrounds to determine whether the same cognitive phenotypes and their relative frequencies would emerge.Participants and Methods:Data from 549 adults with TLE (mean age=27.14 (8.04), 60.47% males) from a tertiary referral hospital in Mumbai, India who had undergone a comprehensive neuropsychological evaluation (minimum two tests in at least 4 of the 5 cognitive domains: memory, language, executive function, attention/processing speed and visuospatial) were analysed using the ICCoDE criteria. The base rate of impairment for individual tests was calculated using a cutoff of 1.5 standard deviations (S.D.) below the normative mean. The cognitive diagnostic criteria were applied, and the distribution and base rate of cognitive phenotypes was compared to the published taxonomy data from the U.S. (McDonald et al., 2022).Results:In comparison to the U.S. cohort, the India group was relatively younger, lower in the education level, had a younger age at seizure onset and a shorter duration of the epilepsy. Application of the IC-CoDE taxonomy using a 1.5 S.D. cutoff revealed an Intact cognitive profile in 48% of patients, Single Domain impairment in 32%, Bi Domain impairment in 15% and Generalised impairment in 5%. These findings were mostly comparable to percentages reported in the U.S. cohorts with Intact profile (47%; c2= 0.158, p=0.690), Single Domain (29%; c2= 46.26, p&lt;0.01), Bi Domain (16%; c2= 0.298, p=0.585) and Generalised (8%; c2= 5.347, p=0.021) impairment. However, the most common impairment in the Single Domain group for the bi/multilingual India population was Memory (38%) followed by Attention (20%) and then Language (13%), diverging from the distribution in the U.S. data with maximum impairment in Language (49%) followed by Memory (32%) in the Single Domain Group.Conclusions:These findings demonstrate that the IC-CoDE can be applied internationally, and the broad taxonomy of cognitive diagnosis holds even in a culturally, linguistically diverse population. Differences in rates of impairments across specific domains emerged with language relatively preserved in the India bi/multilingual population, and memory more frequently impaired than observed in the multi-centre U.S. sample. These findings may reflect differences in demographics, rates of bi/multilingualism, normative data, language tools, or underlying neuropathology, which should be further explored to determine their impact on cognitive profiles.

24 Adaptive Functioning and Academic Achievement in Survivors of Childhood Acute Lymphoblastic Leukemia

Objective:Executive functioning (EF) and socioeconomic status (SES) are associated with functional outcomes (adaptive functioning and academic achievement) in healthy controls and pediatric populations with executive dysfunction. However, these relationships have yet to be investigated in survivors of childhood acute lymphoblastic leukemia (ALL), a population with EF impairment resulting from disease and treatment characteristics. The objective of this study was to examine the associations of functional outcomes with EF and SES (neighborhood-specific variables and academic support) in survivors of childhood ALL.Participants and Methods:Forty-four participants (38.6% female, 72.7% non-Hispanic White, ages 6-17) previously diagnosed with low-risk or standard-risk pre-B cell ALL and treated with chemotherapy-only were included. Participants were evaluated on performance-based measures of EF (cognitive flexibility, verbal fluency, working memory, and processing speed) and academic achievement (word reading and math calculation), and parent-ratings of EF and adaptive functioning. All measures were expressed as T-scores with lower scores indicating better performance. Neighborhood-specific variables were based on participants’ zip codes and census block group, and included area deprivation index (ADI) and child opportunity index (COI). Lower ADI and COI indicate lesser deprivation and greater opportunity. Individualized education plan (IEP) status was used as a proxy of academic support, coded dichotomously as with or without IEP. Percentages of participants showing impairments in functional outcomes were calculated using a cutoff of &gt; 1 SD above the normative mean. Partial correlations were conducted while controlling for age at evaluation, age at diagnosis, sex, and verbal IQ, to examine whether participants with poorer performance-based and parent-rated EF would show reduced functional outcomes. Multiple regression analyses were conducted to evaluate whether neighborhood-specific variables and IEP status would predict functional outcomes while controlling for covariates.Results:Compared to population norms, survivors of childhood ALL showed worse functional outcomes. Within adaptive functioning, 45.5% of participants showed impairment in activities of daily living and leadership. Adaptive functioning was significantly positively correlated with parent-rated, but not performance-based, EF (r=0.694, p&lt;0.001). Compared to female survivors, male survivors were at increased risk for adaptive functioning difficulties (r=-0.401, p&lt;0.05). Impairments for word reading and math calculation were 25% and 41.7%, respectively. Greater math calculation was associated with better verbal fluency (r=0.378, p&lt;0.05) and processing speed (r=0.439, p&lt;0.05). Older participants at evaluation (/3=-0.580, p&lt;0.001) and those without IEP support (ß=0.465, p&lt;0.05) showed better word reading. Lower ADI predicted better verbal fluency (ß=0.282, p=0.041), however, neighborhood-specific variables were not associated with functional outcomes.Conclusions:Prior findings indicate that performance-based measures and parent-ratings assess different constructs of EF. Thus, adaptive functioning may relate more to the behavioral construct of EF than its cognitive construct. Current findings also suggest that male survivors are at increased risk for reduced adaptive functioning, consistent with recent reports that male survivors of ALL are at greater risk for specific neurocognitive outcomes. Overall, functional outcomes may be more strongly related to EF than neighborhood-specific variables. Long-term goals include early screening of adaptive and academic difficulties, targeted intervention, and neuropsychological monitoring to support pediatric survivors’ neurocognitive and psychosocial development.

91 Agent Orange Exposure and Mild Cognitive Impairment in U.S. Vietnam Era Veterans

Objective:US forces used Agent Orange (AO) during the Vietnam War and continued to store/test it at other locations after the war. AO is a powerful herbicide including dioxin, a highly toxic ingredient classified as a human carcinogen. The National Academies of Sciences, Engineering, and Medicine periodically review the literature on the health effects of AO exposure (AOE) and concluded in 2018 that there is sufficient evidence linking AO with a wide range of adverse health outcomes, including neurologic disorders (e.g., Parkinson’s disease). The VA has a list of medical disorders considered presumptive conditions related to AOE. More recently, AOE has been linked to a nearly double risk compared to those without AOE for receiving a dementia diagnosis. To our knowledge, no one has investigated the association of AOE to mild cognitive impairment (MCI), a condition thought to precede dementia.Participants and Methods:We examined men in three waves of the Vietnam Era Twin Study of Aging (VETSA). In wave 3, participants self-reported yes/no to the question of whether they ever had prolonged or serious AOE. MCI was diagnosed by the Jak-Bondi approach. Impairment was defined as 2+ tests within a cognitive domain that were more than 1.5 standard deviations below normative means after adjusting for premorbid cognitive ability. In mixed effects models, we tested the effect of AOE on MCI status. Models were adjusted for age, ethnicity, and non-independence within twin pairs.Results:In wave 3, 12.6% (230) of 1167 participants reported AOE. Those with AOE data had mean ages of 51.1 (wave 1), 56.0 (wave 2), and 61.4 (wave 3). Those with data on both AOE and MCI numbered 861 (wave 1), 900 (wave 2), 1121 (wave 3), and 766 had AOE and MCI at all waves. AOE was significantly related to wave 2 MCI (p &lt; .001), but not to waves 1 and 3 MCI. AOE was significantly associated with the number of time points at which someone met criteria for MCI (p = .011). Analyses were conducted on six cognitive domains used to diagnose MCI, using available participants per wave. At all 3 waves, AOE was significantly associated with lower scores in processing speed (p = .003, p = .004, p = .005, respectively), working memory (p &lt; .001, p = .002, p = .008) and nearly significant at all waves for executive dysfunction (p &lt; .001, p &lt; .001, p = .050). There were two other significant associations [wave 2 memory (p = .038), wave 3 fluency (p = .024)]. The semantic fluency cognitive domain was unrelated to AOE in all waves.Conclusions:AOE was consistently associated with lower processing speed, working memory, and executive dysfunction in males ages 51-61. It was also associated with the number of time points at which one met criteria for MCI in that age range, and with MCI in the mid-fifties. Findings support the idea of a risk for greater cognitive decline in those exposed to AO earlier in their lives, and with a risk for developing MCI.

4 Preoperative International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) Phenotype is Associated with Postoperative Memory Decline Following Temporal Lobectomy

Objective:The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.Participants and Methods:347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of &gt;1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.Results:The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.Conclusions:In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.

37 Cognitive Disengagement Syndrome (CDS; Sluggish Cognitive Tempo) in Pediatric Epilepsy

Objective:Cognitive disengagement syndrome (CDS; previously known as “sluggish cognitive tempo” or SCT) refers to a set of behavioral symptoms characterized by slowed thinking/behavior, daydreaming, and mental fogginess or confusion. It has been described as related to, yet separate from, symptoms associated with Attention-deficit Hyperactivity Disorder (ADHD) inattention. There is a paucity of research on CDS within pediatric epilepsy populations despite substantial risk factors inherent to the disorder and a large proportion of patients with comorbid ADHD. This study therefore describes CDS as reported by parents for a large sample of children with epilepsy. Relationship between epilepsy variables (e.g., number of antiepileptic drugs [AEDs], seizure frequency, seizure type) and CDS symptoms was explored. Additionally, considering the negative association between CDS and academic performance in other populations, the relationship between parentrated CDS and academic risk factors was examined.Participants and Methods:Participants included 151 children with epilepsy (mean age = 11y, range 6-18y; 55% male; IQ&gt;70), referred for outpatient neuropsychological assessment. As part of routine clinical care, parents completed the Penny Sluggish Cognitive Tempo Scale (SCT) and the Colorado Learning Difficulties Questionnaire (CLDQ). Scores and basic demographic information were extracted from an IRB approved clinical database; the IRB granted approval for retrospective chart review to extract additional medical variables. Parent report of CDS included total CDS score and three subdomains: Sleepy/Sluggish, Low Initiation, and Daydreamy. Higher scores represent greater parent-reported difficulties. Independent samples t-tests compared the participants’ means on total CDS and each subdomain to the normative sample. Analysis of variance was conducted to determine differential impact of seizure type (Generalized, Focal, or Multifocal) on total CDS and each subdomain. Correlations between other medical variables, scores on the CLDQ, and parent ratings on the SCT were examined.Results:Parents of children with epilepsy rated overall CDS total and subdomain scores as significantly higher compared to the normative means with highest elevation in symptoms of Low Initiation (p = &lt;.001). Total CDS was associated with increased parent-reported academic difficulties; however, of the three subdomains, only Low Initiation was significantly associated with concerns for academic functioning. Number of AEDs was associated with increased symptoms on the Sleepy/Sluggish subdomain only. Seizure frequency was associated with total CDS and Sleepy/Sluggish symptoms, though this finding is likely mediated by increased number of AEDs for those with more frequent seizures. Seizure type was not associated with significant differences in Total CDS or CDS subdomains.Conclusions:Children with epilepsy are at increased risk for experiencing slowed thinking and cognitive disengagement. Low initiation is particularly elevated in pediatric epilepsy populations, which may lead to increased academic difficulties. Potential interventions targeting low initiation may therefore have benefit in the academic setting for children with epilepsy, regardless of epilepsy type.

Practical adaptive skills in pediatric brain tumor survivors: the contribution of medical factors and social determinants of health

ABSTRACT Pediatric brain tumor survivors demonstrate weaknesses in adaptive functioning, most notably practical adaptive skills; however, the specific areas of weakness within practical skills are unknown. This study examined the aspects of practical adaptive functions that are most impacted in brain tumor survivors, and identified medical and socio-demographic variables that predicted outcomes. The sample included 117 pediatric brain tumor patients seen for a clinical neuropsychological evaluation and whose parents completed the Adaptive Behavior Assessment System, Second or Third Edition. T-tests compared practical adaptive skills to normative means. Correlations examined associations between medical and socio-demographic variables and each of the practical adaptive subscales (Community Use, Home Living, Health & Safety, Self-Care). Significant correlations were entered into linear regression models for each practical adaptive skill. All practical subscales were significantly below the normative mean. Community Use was positively correlated with age at diagnosis and negatively correlated with treatment burden, time since diagnosis, and neighborhood deprivation. Health and Safety was positively correlated with age at diagnosis. Home Living was positively correlated with neighborhood deprivation. Self-Care was positively correlated with age at diagnosis and parental education. Specific medical and socio-demographic factors predicted practical adaptive functioning, highlighting the importance of considering the role of medical and socio-demographic determinants of health on adaptive functioning outcomes in pediatric brain tumors.

Normative Data for the 12-Item Sniffin' Sticks Odor Identification Test in Older Adults.

Quantitative olfactory assessment has demonstrated clinical utility for the evaluation of a range of neurologic, psychiatric, and sinonasal conditions. Here, we provide age, sex, race, and education-specific normative data for the 12-item Sniffin Sticks Odor Identification Test (SSOIT-12) in older Black and White U.S. adults without preclinical or clinical dementia or sinonasal disease. A sample of 2,224 Atherosclerosis Risk in Communities study participants aged 66-89years were included. A normative regression equation was developed using a linear model for the association of age, sex, race, and education with odor identification score. Regression-based normative mean scores and percentiles were generated by age, sex, race, and education groups. Participants (mean age = 74years, 59% women, 20% Black, 48% > high school education) had a mean SSOIT-12 score of 9.8. Age, sex, race, and education were all associated with odor identification performance (all ps < .05). A linear regression model for the predicted SSOIT-12 score was developed for use with an individual's actual SSOIT-12 score in order to calculate the Z-score and corresponding percentile for a specific age, sex, race, and education group. Data are also reported in tabular format. Our study provides SSOIT-12 normative data obtained from a large population of White and Black older adults without preclinical or clinical dementia or sinonasal disease living in the USA. These findings can aid clinicians in assessing the degree of olfactory loss, establishing concordance with a person's perception of olfactory difficulties and quantitatively monitoring changes in olfactory performance over time.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to frontal lobe epilepsy using multicenter data

RationaleThe International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. MethodsNeuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. ResultsThe highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23–40% cognitively intact, 24–29% single domain impairment, 13–20% bi-domain impairment, and 18–33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15–18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. ConclusionsThese results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

Psychometric Properties of the Spinal Cord Injury-Quality of Life (SCI-QOL) Resilience Short Form in a Sample With Spinal Cord Injury

ObjectiveTo explore the psychometric properties (eg, data distribution characteristics, convergent or discriminant validity, internal consistency reliability) of the Spinal Cord Injury-Quality of Life measurement system (SCI-QOL) Resilience 8-item short form (SF) in comparison to the criterion standard resilience measure, Connor Davidson Resilience Scale (CD-RISC) in a sample of individuals with spinal cord injury (SCI). DesignDescriptive statistics were calculated to examine variable data distribution characteristics. Correlation analyses were conducted for convergent and discriminant validity. Reliability statistics were calculated for resilience and other validity measures. SettingGeneral community. ParticipantsIndividuals with SCI (N=202; 51.5% male, 48% female). InterventionsNot applicable. Main Outcome MeasuresPatient-Reported Outcomes Measurement Information System measures (depression, anxiety, ability to participate in social roles and activities, pain intensity, fatigue, sleep disturbance), SCI-QOL short forms (SF) (resilience, positive affect and well-being, mobility), CD-RISC, National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function - perceived stress (NIH Toolbox-perceived stress), and the Satisfaction with Life Scale were administered. ResultsThe mean and SD for the SCI-QOL Resilience SF (mean=48.60; SD=8.20) approximated the normative mean (mean=50, SD=10). The SCI-QOL Resilience SF scores were essentially normally distributed though somewhat kurtotic, with skew=-0.17 and excess kurtosis=1.4; internal consistency reliability was good (Cronbach's alpha=0.89). Convergent validity was supported by significant moderate correlations in expected directions between the SCI-QOL Resilience SF and measures of CD-RISC resilience, depressive symptoms, anxiety, social participation, positive affect and well-being, stress, and satisfaction with life. Discriminant validity was supported by small non-significant correlations between the SCI-QOL Resilience SF and age, sex, injury level, time since injury, pain intensity, mobility, sleep disturbance, and fatigue. ConclusionThe SCI-QOL Resilience SF demonstrated good convergent and discriminant validity. Our study showed that the SCI-QOL Resilience SF is a psychometrically valid tool that can reliably estimate levels of resilience in the SCI population.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (β = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.