Interactions between weight loss and plasma neurodegenerative markers for determining cognitive decline among community-dwelling older adults

This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β42/40 (Aβ42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8y (SD=4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onwards by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test, Digit Symbol Substitution Test, ten MMSE orientation items (MMSEO) and Free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL+lower Aβ42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p<0.0001) and MMSEO (p=0.021), compared to non-WL+higher Aβ42/40. WL+higher NfL (>94.55pg/mL, highest quartile) or progranulin (>38.4ng/mL, three higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO and composite score (all p<0.03), compared to non-WL+lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs. Q4) revealed higher cognitive decline among the WL+lower progranulin group compared to non-WL+lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment.

Measuring implementation fidelity in a cluster-randomized pragmatic trial: development and use of a quantitative multi-component approach

Background In pragmatic trials, on-site partners, rather than researchers, lead intervention delivery, which may result in implementation variation. There is a need to quantitatively measure this variation. Applying the Framework for Implementation Fidelity (FIF), we develop an approach for measuring variability in site-level implementation fidelity. This approach is then applied to measure site-level fidelity in a cluster-randomized pragmatic trial of Music & MemorySM (M&M), a personalized music intervention targeting agitated behaviors in residents living with dementia, in US nursing homes (NHs). Methods Intervention NHs (N = 27) implemented M&M using a standardized manual, utilizing provided staff trainings and iPods for participating residents. Quantitative implementation data, including iPod metadata (i.e., song title, duration, number of plays), were collected during baseline, 4-month, and 8-month site visits. Three researchers developed four FIF adherence dimension scores. For Details of Content, we independently reviewed the implementation manual and reached consensus on six core M&M components. Coverage was the total number of residents exposed to the music at each NH. Frequency was the percent of participating residents in each NH exposed to M&M at least weekly. Duration was the median minutes of music received per resident day exposed. Data elements were scaled and summed to generate dimension-level NH scores, which were then summed to create a Composite adherence score. NHs were grouped by tercile (low-, medium-, high-fidelity). Results The 27 NHs differed in size, resident composition, and publicly reported quality rating. The Composite score demonstrated significant variation across NHs, ranging from 4.0 to 12.0 [8.0, standard deviation (SD) 2.1]. Scaled dimension scores were significantly correlated with the Composite score. However, dimension scores were not highly correlated with each other; for example, the correlation of the Details of Content score with Coverage was τb = 0.11 (p = 0.59) and with Duration was τb = − 0.05 (p = 0.78). The Composite score correlated with CMS quality star rating and presence of an Alzheimer’s unit, suggesting face validity. Conclusions Guided by the FIF, we developed and used an approach to quantitatively measure overall site-level fidelity in a multi-site pragmatic trial. Future pragmatic trials, particularly in the long-term care environment, may benefit from this approach. Trial registration Clinicaltrials.gov NCT03821844. Registered on 30 January 2019, https://clinicaltrials.gov/ct2/show/NCT03821844.

Hippocampal Subfield Volumes and Cognitive Function in Schizophrenia and Mood Disorders

<b><i>Introduction:</i></b> The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD). <b><i>Methods:</i></b> The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group. <b><i>Results:</i></b> The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score. <b><i>Conclusion:</i></b> Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.

Early spectral EEG in preterm infants correlates with neurocognitive outcomes in late childhood

Background Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We aimed to investigate whether there is an association between early postnatal EEG and neurocognitive outcomes in late childhood. Methods This study is an observational prospective cohort study of premature infants with a gestational age <28 weeks. The total absolute band powers (tABP) of the delta, theta, alpha, and beta bands were analyzed from EEG recordings during the first three days of life. At 10–12 years of age, neurocognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th edition (WISC-IV), Vineland adaptive behavior scales 2nd edition, and Behavior Rating Inventory of Executive Function (BRIEF). The mean differences in tABP were assessed for individuals with normal versus unfavorable neurocognitive scores. Results Twenty-two infants were included. tABP values in all four frequency bands were significantly lower in infants with unfavorable results in the main composite scores (full intelligence quotient, adaptive behavior composite score, and global executive composite score) on all three tests (p < 0.05). Conclusions Early postnatal EEG has the potential to assist in predicting cognitive outcomes at 10–12 years of age in extremely premature infants <28 weeks’ gestation. Impact Evidence regarding the value of early postnatal EEG in long-term prognostication in preterm infants is limited. Our study suggests that early EEG spectral analysis correlates with neurocognitive outcomes in late childhood in extremely preterm infants. Early identification of infants at-risk of later impairment is important to initiate early and targeted follow-up and intervention.

Neurodevelopmental outcomes following preterm birth and the association with postmenstrual age at discharge

Objective: To 1) define the prevalence of motor, cognitive, and language delays in preterm infants born < 32 weeks estimated gestational age (EGA) and 2) identify the relationship between the timing of discharge from the NICU and neurodevelopmental outcome in early childhood. Study Design: This retrospective study of 176 preterm infants born < 32 weeks EGA and hospitalized in a level IV NICU captured medical factors, including timing of discharge, from the NICU stay. Standardized developmental testing at 1-2 years corrected age was conducted in the newborn follow-up clinic. Results: At 1-2 years corrected age, the sample had an average cognitive composite score of 91.5 ± 17.4, language composite score of 84.5 ± 17.3, and motor composite score of 88.9 ± 18.4. Lower EGA at birth, necrotizing enterocolitis, patent ductus arteriosus, and oxygen requirement for > 28 days were independently associated with higher postmenstrual age (PMA) at NICU discharge. After controlling for known risk factors, higher PMA at discharge was associated with poorer cognitive outcome [p < 0.001, (-0.16, -0.07), β = -0.35], poorer language outcome [p = 0.049 (-0.10, 0.00), β = -0.15] and poorer motor outcome [p < 0.001, (-0.14, -0.05), β = -0.30]. Conclusion: Poorer cognitive, language, and motor outcomes were associated with longer hospitalization, even after controlling for medical risk factors known to be associated with poorer outcome. This provides further evidence for the potential role of the environment that may be impacting the developmental outcomes of infants hospitalized in the NICU.

The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation

Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied. Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. Methods: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants ( n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session. Results: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. Conclusions: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. Clinical Trial Registration: EudraCT ( https://www.clinicaltrialsregister.eu/ ) number: 2018-000978-30.

Blended Social Skills Intervention for Students Identified as Emotionally and Behaviorally Disturbed

The purpose of this study was to evaluate a nine-week blended learning social skills intervention for high school students identified as being at risk for emotional and behavioral disorders. Exploring how social skills interventions improve students' social and emotional deficits aids in the development of an engaging curriculum. This quantitative study utilized a pretest-posttest method. High school students identified as being at risk for emotional and behavioral disorders and their special educators were invited to complete the researcher-designed social skills intervention with a corresponding pre- and post-test. There were no statistically significant differences between the pre- and post-test scores for the students or the special educator. The SEARS' social-emotional domains were all found to be statistically significant predictors of the students' total composite score. Gender was found to be a significant predictor of the student's total composite score. Implications of the study include strategies for developing interventions at the high school level.

Immediate effect of stabilization exercises versus conventional exercises of the trunk on dynamic balance among trained soccer players

Background: Trunk stability is key in controlling body balance and movements. Trunk Stabilization Exercises (TSE) and Conventional Trunk Exercises (CTE) are performed to improve dynamic balance. The authors have previously reported that dynamic balance was improved by a 12-week and 6-week TSE program. However, there is a dearth of research on its immediate effect on dynamic balance in trained soccer players. Objective: To compare the immediate effeect of TSE with that of CTE on dynamic balance in trained soccer players. Methods: Forty-eight male soccer players (24.60 ffi 1.38 years) participated in this crossover study, wherein each participant took part in three exercise sessions: TSE, CTE, and No Exercise control (NE), each consisting of three steps: pre-test, intervention and post-test, with an interval of one week between each exercise condition. To assess dynamic balance, the Y Balance Test-Lower Quarter (YBT-LQ) score in the anterior, posteromedial, and posterolateral directions was measured before and 5 minutes after each intervention. Results: The YBT-LQ composite score was significantly improved after TSE (0.51) as compared to CTE (0.22) and NE (0.04) (p < 0.05). Furthermore, in TSE and CTE conditions, YBT-LQ scores of the posterolateral and posteromedial directions significantly improved at the post-test (p < 0.05). Conclusions: Both TSE and CTE are effective in immediately improving dynamic balance; however, TSE showed greater improvement as compared to the latter. Immediate improvements in the posteromedial and posterolateral directions of the YBT-LQ were demonstrated after performing the TSE and CTE.

Immunohistochemical Analysis of Prostein Expression in Archived Prostatic Core Biopsies from Prostate Cancer Patients in Western Kenya

Background Prostate cancer is the leading cause of cancer-associated mortality in men. Most of the current biomarkers for detection of the disease have low sensitivity and specificity. Prostein is a newly reported prostate cancer biomarkers whose diagnostic utility can help in early detection of the disease. Nonetheless, previous studies have utilized limited number of samples to evaluate its immunohistochemistry (IHC) and reports on the African population are not available. The current study aimed to determine the prostein expression in archived prostatic core biopsies from prostate cancer patients in Western Kenya. Materials and Methods This was a retrospective study conducted on malignant and benign prostatic tissue core biopsies of 106 patients who underwent prostate core biopsy at Jaramogi Oginga Odinga Teaching and Referral Hospital and division of urology at Synergy Clinics, Kisumu between January 2018 to May 2021. Immunohistochemical technique was performed on each of the 106 samples and on the following non-prostatic male control biopsies; Testis, Penis, Liver and Esophagus. Cellular location of prostein staining was evaluated at X40, X100 and X400 magnification using a light microscope and was classified as cytoplasmic or nucleocytoplasmic. Intensity of prostein expression was assessed for each core biopsy at similar magnification and graded according the immunohistochemistry composite score. Results The biopsies had been obtained from men whose mean (SE) age was 72.00±0.93 years. 95.3% (101) of the biopsies were malignant and 4.7% (5) were benign. Four non-prostatic male tissues were included. 97% of malignant and all the benign prostate tissue stained positive for prostein whereas the four non-prostatic male tissues were negative. Staining intensities were weak (24.5%), Moderate (17.0%), strong (55.7%) and non-stained (2.8%). The staining was highly immunolocalized within the cytoplasm (95.1% cases) as compared to nucleocytoplasmic (2.0% cases). The mean immunoreactivity composite score was 1.91±0.96 (0.0-3.14). Strongly stained sections had a punctate plasma membrane staining pattern clustered within the cytoplasm in a perinuclear location whereas the weakly stained sections had faint and punctate coarse brown cytoplasmic granular appearing. Conclusion Prostein is exclusively expressed in benign and malignant prostate tissue with a higher cytoplasmic granular staining pattern in the present population. These findings suggest that prostein diagnostic utility is applicable in the current study population and routine IHC diagnosis of prostate cancer may be recommended.

Association of Self-Reported and Device-Measured Sedentary Behaviour and Physical Activity with Health-Related Quality of Life among European Older Adults

Human movement behaviours such as physical activity (PA) and sedentary behaviour (SB) during waking time have a significant impact on health-related quality of life (HRQoL) in older adults. In this study, we aimed to analyse the association between self-reported and device-measured SB and PA with HRQoL in a cohort of community-dwelling older adults from four European countries. A subsample of 1193 participants from the SITLESS trial (61% women and 75.1 ± 6.2 years old) were included in the analysis. The association between self-reported and objective measures of SB and PA with HRQoL were quantified using Spearman’s Rho coefficients. The strength of the associations between self-reported and device-measured PA and SB with self-rated HRQoL (mental composite score, MCS; physical composite score, PCS) were assessed through multivariate multiple regression analysis. Self-reported and device-measured PA and SB levels showed significant but poor associations with PCS (p < 0.05). The association with MCS was only significant but poor with self-reported light PA (LPA) and moderate-to-vigorous PA (MVPA). In conclusion, the findings of this study suggest that both self-reported and device-measured PA of all intensities were positively and significantly associated, while SB was negatively and significantly associated with the PCS of the SF-12.