Search

BackgroundIndividuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross-sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS.MethodBaseline SIB, BPT and DLD performances from 100 individuals (no dementia=68, possible dementia=16 & probable dementia=16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression.ResultsThe SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC)=0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC=0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC=0.77 and 0.67, respectively).ConclusionsResults suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS.

One major obstacle to the accurate diagnosis of ADHD in college students is malingering, although many symptom self-report measures used in the diagnostic process do not contain validity scales to identify feigners. The Infrequency Index (CII) for the Conners’ Adult ADHD Rating Scale–Self-Report: Long Version (CAARS-S: L) was developed in response to this concern, although further validation of this index is needed. Another topic of interest in ADHD malingering research is the increasing use of online assessments. However, little is known about how ADHD is malingered in an online format, particularly on the CAARS-S: L. The current study utilized a coached simulation design to examine the feigning detection accuracy of the CII and provide initial results on the effect of administration format (paper vs. online) on CAARS-S: L profiles. Data from 139 students were analyzed. Students with ADHD and students instructed to feign the disorder produced statistically comparable elevations on seven of eight CAARS-S: L clinical scales. Clinical scale elevations were generally comparable between paper and online forms, although some differences in the clinical and simulated ADHD groups suggest the need for further research. The CII demonstrated modest sensitivity (0.36) and adequate specificity (0.85) at the recommended cut score across administration formats. Specificity reached desirable levels (>= .90) at a raised cut score. These values were similar across administration formats. Results support the use of the CII and online CAARS-S: L form

Objective: Informant ratings of adaptive functioning are a valuable source of information that can support diagnosis and treatment planning and monitor change. The Adaptive Behavior Assessment System (ABAS-II) and Vineland Adaptive Behavior Scales (VABS-II) are well-known adaptive functioning questionnaires used in clinical practice. This study assessed the correspondence between ABAS-II and VABS-II composite scales in adults with Down Syndrome (DS). Method: Participants were selected from a cohort of 110 adults with DS involved in a longitudinal study examining Alzheimer’s risk. Participants were selected if they had informant ratings on both the ABAS-II and VABS-II at the same measurement wave (n = 85; M = 41.9 years-old, SD = 10.8; 55.3% female; 96.5% White). Due to non-normality, non-parametric correlations examined convergent validity of the ABAS-II and VABS-II standard scores. Results: The composite scores of similar constructs from each measure correlated significantly (ps Conclusion(s): The ABAS-II and VABS-II composites were strongly correlated, capturing similar adaptive domains. However, there was a greater chance of being rated as low functioning on the VABS-II compared to the ABAS-II, which may have diagnostic implications for clinical and research work in DS.

Background: Chemotherapy-induced cognitive impairment (CICI), ‘chemo-brain,’ involves concentration and executive functioning difficulty and slowed processing speed and memory. Although cognitive changes in CICI can be subtle and difficult to quantify, CICI affects up to 75% of cancer survivors and impacts quality of life. Objectives: The objective of our study was to add to the definition of CICI by quantifying changes in specific cognitive domains before and after administration of platinum/taxane-based chemotherapy in gynecologic cancer patients using a tailored battery of neurocognitive tests. Methods: Following institutional review board approval, chemotherapy-naive gynecologic cancer patients scheduled to receive six cycles of intravenous platinum/taxane-based chemotherapy were identified. Baseline demographic, social, and clinical characteristics were obtained. Eleven neurocognitive assessments measured cognitive domains of interest (Table 1), including a brief cognitive screen, evaluation of fine motor skills, verbal fluency, working memory, information processing speed, visuospatial learning and memory, attention, mental flexibility, and abstract problem-solving skills. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and Psychiatric Diagnostic Screening Questionnaire assessed emotional functioning. The Functional Assessment of Cancer Therapy - Cognitive Function assessed self-perceived cognitive functioning. Testing was performed prior to the first and three to four weeks after the last cycle of chemotherapy. Descriptive statistics identified trends in individual indices of cognitive dysfunction and quality of life. Results: Fourteen patients enrolled and nine were eligible for complete analyses. The mean age was 60.6 years. The mean full scale intelligence quotient prior to therapy was 103.5. Most patients were White (8/9, 89%), had obtained at least a Bachelor's degree (5/9, 55.6%), and were diagnosed with high grade (6/9, 66.7%) stage III or IV disease (5/9, 55.6%). The majority of patients declined on cognitive screening performance (5/9, 55.6%) as well as worse scores on indices of attention (7/9, 77.8%), mental flexibility (5/8, 62.5%) verbal learning (5/9, 55.6%), and fine motor skills (5/9, 55.6%) after completion of chemotherapy. Most patients improved on indices of verbal memory (7/9, 77.8%), visuospatial learning (6/8, 75%), and verbal fluency (5/9, 55.6%). Despite changes in indices of cognitive function, most patients’ perceived quality of life improved (5/9, 55.6%) after chemotherapy. Download : Download high-res image (219KB) Download : Download full-size image Conclusions: Although gynecologic cancer patients complain of CICI, there is discrepancy regarding its incidence and affected cognitive domains. This pilot study highlights attention and mental flexibility as indices of cognitive dysfunction that may be at risk following receipt of chemotherapy in gynecologic cancer patients. Future research may focus on targeted assessment strategies.

Summary Background Adults with Down syndrome are at an ultra-high risk of Alzheimer's disease, but diagnosis of Alzheimer's disease in this population is challenging. We aimed to validate the clinical utility of plasma neurofilament light chain (NfL) for the diagnosis of symptomatic Alzheimer's disease in Down syndrome, assess its prognostic value, and establish longitudinal changes in adults with Down syndrome. Methods We did a multicentre cohort study, including adults with Down syndrome (≥18 years), recruited from six hospitals and university medical centres in France, Germany, Spain, the UK, and the USA, who had been assessed, followed up, and provided at least two plasma samples. Participants were classified by local clinicians, who were masked to biomarker data, as asymptomatic (ie, no clinical suspicion of Alzheimer's disease), prodromal Alzheimer's disease, or Alzheimer's disease dementia. We classified individuals who progressed along the Alzheimer's disease continuum during follow-up as progressors. Plasma samples were analysed retrospectively; NfL concentrations were measured centrally using commercial kits for biomarker detection. We used ANOVA to evaluate differences in baseline NfL concentrations, Cox regression to study their prognostic value, and linear mixed models to estimate longitudinal changes. To account for potential confounders, we included age, sex, and intellectual disability as covariates in the analyses. Findings Between Aug 2, 2010, and July 16, 2019, we analysed 608 samples from 236 people with Down syndrome: 165 (70%) were asymptomatic, 32 (14%) had prodromal Alzheimer's disease, and 29 (12%) had Alzheimer's disease dementia; ten [4%] participants were excluded because their classification was uncertain. Mean follow-up was 3·6 years (SD 1·6, range 0·6–9·2). Baseline plasma NfL concentrations showed an area under the receiver operating characteristic curve of 0·83 (95% CI 0·76–0·91) in the prodromal group and 0·94 (0·90–0·97) in the dementia group for differentiating from participants who were asymptomatic. An increase of 1 pg/mL in baseline NfL concentrations was associated with a 1·04-fold risk of clinical progression (95% CI 1·01–1·07; p=0·0034). Plasma NfL concentrations showed an annual increase of 3·0% (95% CI 0·4–5·8) per year in the asymptomatic non-progressors group, 11·5% (4·9–18·5) per year in the asymptomatic progressors group, and 16·0% (8·4–24·0) per year in the prodromal Alzheimer's disease progressors group. In participants with Alzheimer's disease dementia, NfL concentrations increased by a mean of 24·3% (15·3–34·1). Interpretation Plasma NfL concentrations have excellent diagnostic and prognostic performance for symptomatic Alzheimer's disease in Down syndrome. The longitudinal trajectory of plasma NfL supports its use as a theragnostic marker in clinical trials. Funding AC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jerome Lejeune Foundation, Medical Research Council, National Institute for Health Research, EU Joint Programme–Neurodegenerative Disease Research, Alzheimer's society, Deutsche Forschungsgemeinschaft, Stiftung fur die Erforschung von Verhaltens und Umwelteinflussen auf die menschliche Gesundheit, and NHS National Institute of Health Research Applied Research Collaborations East of England, UK.

Objective:To determine whether primitive reflexes serve as an indicator of dementia in adults with Down syndrome (DS), we collected neurologic examination data, cognitive and behavioral assessments, and clinical consensus diagnoses of dementia from 92 adults with DS.Methods:In a cross-sectional, observational study of a regional cohort, chi-square and Fisher’s exact tests examined individual reflexes across diagnostic group (No, Possible, or Probable Dementia). In 64 participants with all 8 reflexes assessed, the number of primitive reflexes was assessed as a predictor of diagnosis using age-controlled multinomial logistic regression and of performance on clinical assessments (Brief Praxis Test [BPT], Severe Impairment Battery [SIB], and the Dementia Questionnaire for People with Learning Disabilities [DLD] using age-adjusted linear regression.Results:Primitive palmomental, grasp, snout, and suck reflexes were more frequent in individuals with probable dementia, but all participants showed at least one primitive reflex. Multiple primitive reflexes in combination served as a better indicator of dementia, with each additional abnormal reflex tripling probability of Probable Dementia group membership controlling for age. Abnormal reflex count was not associated with direct assessment of cognition and praxis (SIB and BPT) but associated with informant ratings of cognitive and behavioral functioning (DLD).Conclusions:The presence of multiple reflexes serves as an indicator of dementia status in DS as a supplement to direct assessment of cognition and praxis. The reflex examination may serve as a tool in the multimethod evaluation for dementia in DS, as it appears unaffected by intellectual disability and language mastery.

Mild cognitive changes, including executive dysfunction, are seen in Parkinson's Disease (PD). Approximately 30% of individuals with PD develop Parkinson's disease dementia (PDD). Mild cognitive impairment (MCI) has been identified as a transitional state between normal cognition and dementia. Although PD-MCI and its cognitive correlates have been increasingly studied as a risk indicator for development of PDD, investigations into the PD-MCI construct have yielded heterogeneous findings. Thus, a typical PD-MCI cognitive profile remains undefined. The present meta-analysis examined published cross-sectional studies of PD-MCI and cognitively normal PD (PD-CN) groups to provide aggregated effect sizes of group test performance by cognitive domain. Subsequently, longitudinal studies examining PD-MCI to PDD progression were meta-analyzed. Ninety-two cross-sectional articles of PD-MCI vs. PD-CN were included; 5 longitudinal studies of PD-MCI conversion to PDD were included. Random effects meta-analytic models were constructed resulting in effect sizes (Hedges' g) for cognitive domains. Overall performance across all measures produced a large effect size (g = 0.83, 95% CI [0.79, 0.86], t2 = 0.18) in cross-sectional analyses, with cognitive screeners producing the largest effect (g = 1.09, 95% CI [1.00, 1.17], t2 = 0.19). Longitudinally, overall measures produced a moderate effect (g = 0.47, 95% CI [0.40, 0.53], t2 = 0.01), with measures of executive functioning exhibiting the largest effect (g = 0.70, 95% CI [0.51, 0.89], t2 = 0.01). Longitudinal effects were made more robust by low heterogeneity. This report provides the first comprehensive meta-analysis of PD-MCI cognitive outcomes and predictors in PD-MCI conversion to PDD. Limitations include heterogeneity of cross-sectional effect sizes and the potential impact of small-study effects. Areas for continued research include visuospatial skills and visual memory in PD-MCI and longitudinal examination of executive dysfunction in PD-MCI.

Down syndrome (DS) is a genetic disorder caused by full or partial triplication of chromosome 21 (HSA21). Key genes related to Alzheimer’s disease (AD) pathology reside on HSA21, causing lower life expectancy due to dementia. Triplication of the amyloid precursor protein gene is associated with rapid accumulation of amyloid beta, one neuropathological feature of AD. Accumulation of amyloid beta promotes neurofibrillary tangle accumulation in the brain, the other feature of AD neuropathology. While virtually all individuals with DS have significant AD neuropathology by age 40, a clinical diagnosis for dementia is generally not made until the age of 55. This gap between accumulating neuropathology and clinical symptomatology represents a period of minimal or subtle symptoms not detectible by current clinical measures. Recent research has demonstrated possible contributions of cerebrovascular disease and possible early markers of prodromal disease. Improved diagnostic accuracy and earlier diagnosis are critical for developing future research and clinical trials to address AD in Down syndrome.

Author(s): Koehl, Lisa; Harp, Jordan; Van Pelt, Kathryn L; Head, Elizabeth; Schmitt, Frederick A | Abstract: IntroductionEarly detection ofndementia symptoms is critical in Down syndrome (DS)nbutncomplicated by clinical assessmentnbarriers. The current study aimed to characterize cognitive and behavioral impairment using longitudinal trajectories comparing several measures of cognitive and behavioral functioning.MethodsMeasures included global cognitive status (Severe Impairment Battery [SIB]), motor praxis (Brief Praxis Test [BPT]), and clinical dementia informant ratings (Dementia Questionnaire for People with Learning Disabilities [DLD]). One-year reliability was assessed using a two-way mixed effect, consistency, single measurement intraclass correlation among non-demented participants. Longitudinal assessment of SIB, BPT, and DLD was completed using linear mixed effect models.ResultsOne-year reliability (n = 52; 21 male) was moderate for DLD (0.69 to 0.75) and good for SIB (0.87) and BPT (0.80). Longitudinal analysis (n = 72) revealed significant age by diagnosis interactions for SIB (F(2, 115.02) = 6.06, P = .003), BPT (F(2, 85.59) = 4.56, P = .013), and DLD (F(2, 103.56) = 4.48, P = .014). SIB progression (PR) had a faster decline in performance versus no-dementia (ND) (t(159) = -2.87; P = .013). Dementia had a faster decline in BPT performance versus ND (t(112) = -2.46; P = .041). PR showed quickly progressing scores compared to ND (t(128) = -2.86; P = .014).DiscussionCurrent measures demonstrated moderate to good reliability. Longitudinal analysis revealed that SIB, BPT, and DLD changed with age depending on diagnostic progression; no change rates were dependent on baseline cognition, indicating usefulness across a variety of severity levels in DS.

Author(s): Van Pelt, Kathryn L; Koehl, Lisa; Caban-Holt, Allison; Anderson-Mooney, Amelia; Head, Elizabeth; Schmitt, Frederick A | Abstract: IntroductionThe striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD.MethodsTwenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle).ResultsAll participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. Gait velocity had stronger associations with clinical dementia assessments than age or diagnosis.DiscussionA dual-task gait paradigm is feasible to conduct with adults with DS and is associated with age and cognitive impairment. Dual-task gait may serve as an indicator of early stage dementia in DS.

e24051 Background: Chemotherapy-induced cognitive impairment (CICI) is a common side effect of cancer therapy, affecting up to 75% of cancer patients. Oxidative stress is thought to play a key role in CICI and patients who have been treated with chemotherapy have demonstrated biochemical brain changes on magnetic resonance spectroscopy (MRS). Methods: Following institutional review board approval, chemotherapy-naïve gynecologic cancer patients scheduled to receive intravenous platinum/taxane-based chemotherapy were identified. The primary objective of this study was identification of chemotherapy-induced cognitive function changes using the Montreal Cognitive Assessment (MoCA) tool. This exploratory analysis evaluates correlations between changes in MoCA scores, oxidative analytes TNF-a, protein carbonyls (PC), and 4-hydroxynonenal (HNE) protein adducts, and MRS metabolic signals. Testing was performed at baseline and three weeks post-treatment. Simple linear regression was performed to evaluate the correlation between changes in MoCA scores and oxidative metabolites. Results: Fourteen patients were enrolled. Six patients had complete pre/post oxidative stress data, and four patients had complete pre/post MRS data. Five of six had decreased PC values (mean net change -15.17%, SD 0.15), half had increased HNE levels (mean net change +16.38%, SD 0.38), and four of six had decreased TNF-a values (mean net change -15.10%, SD 0.27) (Table). MoCA scores were positively correlated with serum PC levels ( r = 0.86, p = 0.03) and not significantly correlated with TNF-a or HNE levels. Of those with complete pre/post MRS data, all patients had a decrease in glycerophosphocholine + phosphocholine/creatinine ratio signals. MoCA raw score prior to and after completion of chemotherapy. A higher score indicates improved test performance. Positive percentage of oxidative stress markers (PC, HNE, TNF-a) indicates increased post-therapy levels compared to pre-therapy. Conclusions: In this study, we evaluated candidate oxidative stress serum markers and changes in MRS metabolite signals for CICI. Serum PC levels correlate with cognitive screening scores. For patients undergoing brain imaging, MRS evaluation for individual choline components, glycerophosphocholine and phosphocholine, may serve as an additional marker of oxidative damage. This pilot study highlights the potential value of serum PC levels and dedicated brain imaging for signs of oxidative stress, including MRS, to guide future CICI identification studies. Clinical trial information: NCT03324945. [Table: see text]

Sports concussions are recognized as significant injuries among young athletes. Research demonstrates that return-to-play prior to becoming asymptomatic has significant repercussions including sustained cognitive deficits. Many programs have begun to use computerized testing rather than traditional neuropsychological tests to (a) determine baseline performance, (b) track symptoms, and (c) measure symptoms following concussion. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is one such tool. The current study examined ImPACT's convergent and discriminant validity by comparing scores from sports-related concussion athletes (SRC) to those from nonconcussed controls (CTL). SRC included 29 athletes, ages 12-16, referred for neuropsychological assessment following sports-related concussions. CTL included 25 healthy athletes, ages 12-16, who were concussion-free in the past year. Overall, results showed general support for ImPACT, when used to screen cognition. In fact, all ImPACT domains successfully differentiated between SRC and CTL athletes. Evidence supporting appropriate convergent validity was best for the Visual Memory domain. Further, ImPACT domains demonstrated variable discriminant validity. Overall examination of validity demonstrated that ImPACT has some weaknesses but may have utility in detecting postconcussion cognitive impairment.

Psychologists often use the Minnesota Multiphasic Personality Inventory (MMPI) and, more recently, its successor, the MMPI-2, to assess personality and psychological disturbances following traumatic brain injury (TBI). The present meta-analysis examined the pattern of mean Hedges’ d values on MMPI-2 validity (L, F, K) and clinical (1–4, 6–0) scales in individuals with TBI. Database keyword searches yielded ten studies providing post-TBI MMPI-2 profiles. Studies were required to include a pure TBI sample, individuals who were ≥18 at injury, and means and standard deviations for most MMPI-2 clinical scales. Analyses showed large effects for MMPI-2 scales F, 1, 2, 3, 7, and 8. Using Q statistics, moderating effects were found for TBI severity on scale 7 and for compensation-seeking/litigation status on scales 1, 2, 3, and 7. No significant effects were found for time post-injury. The available information was insufficient to examine the effect of lesion location, pre-injury personality and psychopathology, or time post-injury for samples with differing injury severities on MMPI-2 profiles. Results suggest that individuals with TBI report significant levels of psychopathology that may be moderated by TBI severity and compensation-seeking/litigation status. Discussion includes a literature critique given the meta-analytic findings and implications for future study of personality following TBI.

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.

Objective Identifying risk factors is important in adolescent sports concussions. This study aimed to explore the relationship between affective symptoms and physical symptoms in youth concussions. Design Athletes were split into two groups: self-reported emotional symptoms (irritability/aggression, anxiety, depression, apathy, and/or labile mood; EMO, n=22) and a control group without emotional symptoms (CON, n=15). Groups were examined for differences between post-concussive symptoms and peri-concussive factors. Setting Outpatient clinic. Participants 37 concussed adolescents age 12–17 with persisting concussion symptoms were assessed. Concussion diagnoses were indicated by traumatically induced alterations in mental status (with or without LOC), disruption in brain functioning (memory loss/neurological deficits), and other physiologic symptoms post-concussion. Those with baseline psychiatric history and/or special education were excluded. Assessment of risk factors Post-concussive symptom variable relationships were assessed. Outcome measures group differences were analysed using ANOVAs. Results No differences between positive LOC, positive amnesia, or post-concussive criteria existed, indicating likely comparable severity. While there were no group differences for number of concussions, headaches, or nausea, those in EMO were significantly more likely to endorse photo-sensitivity (p=0.003, F=10.155) and phono-sensitivity (p=0.007, F=8.108). Both anxiety and irritability/aggression were significantly (p Conclusions Results indicate that adolescents who self-report emotional difficulties following sports concussion are more likely to endorse some physical symptoms, particularly photo-sensitivity and phono-sensitivity. Those experiencing anxiety or irritability are also more likely to experience increased attentional difficulties. Competing interests None.

Objective To assess whether irritability and aggression are viable indicators of persistent post-concussive symptoms in adolescents. Design Group differences between those diagnosed with concussions were analysed using ANOVAs (p Setting Outpatient clinic. Participants 46 concussed adolescents age 12–17 with persisting concussion symptoms were assessed. Athletes were split into two groups: those endorsing irritability/aggression (AGG, n=24) and a control group of those denying irritability/aggression (CON, n=22). Those with baseline psychiatric history and/or special education were excluded. Assessment of risk factors Post-concussive symptom variable relationships were assessed. Outcome measures group differences were analysed using ANOVAs. Results Adolescents endorsing irritability/aggression reported more fatigue (p=0.002), disordered sleep (p=0.001), anxiety (p=0.028), depression (p=0.003), and mood lability (p Conclusions Results indicate that adolescents with self-reported irritability and aggression post-concussion were more likely to display more affective symptoms than those who did not endorse irritability and aggression following concussions. They were also more likely to complain of fatigue and disordered sleep. These findings suggest that change in level of irritability/aggression could potentially serve as an identifiable indicator for parents and coaches to recognise when an adolescent is not recovering well post-concussion. Competing interests None.