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The epsilon4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer's disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21-87 years of age (n=134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE epsilon4 and correlation between SNPs (linkage disequilibrium). APOE epsilon4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis. [ABSTRACT FROM AUTHOR]

Corpus callosum area has been examined in neurodegenerative diseases as a marker for cortical pathology and for differential diagnosis; however, it has not been examined in Parkinson's disease (PD). We compared callosal area in patients with PD and PD with dementia (PDD) to healthy controls and patients with Alzheimer's disease (AD). We subsequently compared our results to a meta-analysis of studies examining callosal area in AD, frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). For the imaging study, midsagittal T1-weighted MRIs were analyzed and the callosal area was determined in patients with PD (n = 24), PDD (n = 25), AD (n = 16) and controls (n = 27). The meta-analysis combined results from all publications (Medline or PubMed) representing unique samples and measuring callosal area in AD, FTD, PSP, and CBD. We found that PD and PDD patients did not show statistically significant callosal atrophy compared to controls (effect size d, 95% CI, d = 0.13, -0.26 to 0.52, and d = 0.05, -0.44 to 0.33, respectively) or AD. The AD patients had a significant loss of callosal area compared to controls (d = -0.58, -1.01 to -0.15). Dementia severity was correlated with total callosal atrophy in AD (R = 0.66, p < 0.01) but not in PDD patients (R = 0.18, p > 0.1). The meta-analysis revealed significant combined effect sizes for callosal atrophy of: AD (d = -1.03, -1.13 to -0.93), FTD (d = -1.21, -1.56 to -0.86), PSP (d = -1.09, -1.38 to -0.81), and CBD (d = -1.80, -2.18 to -1.43). We conclude that PD and PDD patients do not have callosal atrophy in contrast to other neurodegenerative diseases, including AD. Callosal atrophy was correlated with dementia severity in patients with AD but not PDD. [ABSTRACT FROM AUTHOR]

Objective: To estimate recent temporal trends in delivery by cesarean during the past decade and the proportion of vaginal deliveries after prior caesarean in the United Kingdom. Methods: We conducted a cohort study using information from the General Practice Research Database. We identified all women with 1 or more deliveries between January 1990 and December 1999 and determined the method(s) of delivery. We estimated the proportion of women with vaginal delivery after cesarean in a subcohort who had at least 3 years of follow-up. Results: We identified 39,938 cesareans among 271,663 deliveries (14.7%), with an increase from 12.5% in 1990 to 18.3% in 1999. The proportion of cesarean deliveries increased with age and increased over time in all age groups except women aged younger than 20 years. Among 26,480 women with a caesarean delivery between 1990 and 1996, 7,649 (28.9%) had a subsequent delivery. The proportion of vaginal delivery after prior cesarean decreased from 45% in 1991 to 37% in 1999. Conclusion: Cesarean deliveries increased as a proportion of all deliveries in the United Kingdom during the past decade, and the proportion of vaginal delivery after prior cesarean decreased. Still, the proportion of cesarean deliveries is lower and the proportion of vaginal deliveries after prior cesarean is higher in the United Kingdom than in the United States. Level Of Evidence: II-2. [ABSTRACT FROM AUTHOR]

Background: Concern has been raised that the risk of venous thromboembolism (VTE) in users of the ORTHO EVRA patch is higher compared to users of oral contraceptives (OCs).Study Design: We identified idiopathic cases of VTE and controls, matched on age and index date, from among women in the United States PharMetrics/IMS and MarketScan databases who were current users of the patch or levonorgestrel-containing OCs with 30 mcg of ethinyl estradiol. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).Results: The ORs (95% CI) for VTE in users of the patch compared to levonorgestrel-containing OCs were 2.0 (0.9-4.1) and 1.3 (0.8-2.1) in the PharMetrics and MarketScan databases, respectively. ORs (95% CI) restricted to women aged 39 years or younger were 1.4 (0.6-3.0) and 1.2 (0.7-2.0), respectively.Conclusion: These results provide evidence that the risk of idiopathic VTE in users of the patch is not materially different than that of users of levonorgestrel-containing OCs in women aged 39 years or younger. We cannot rule out some increase in the risk in women aged 40 years or older. [ABSTRACT FROM AUTHOR]

Objective: To analyze dietary supplement usage data from 494 older adults, aged 65 to 101 years.Setting: Community dwellers living independently of institutionalized care.Design: All dietary supplements, including botanicals, were recorded to aid in assessing the health status of older adults.Participants: 1) 224 individuals enrolled in a study that follows the health of persons 85 years and older (oldest-old) in Klamath County, a non-metropolitan area in southern Oregon; 2) 134 participants of oldest-old age living in the metropolitan Portland area, enrolled in a randomized clinical trial of GBE biloba extract (GBE) for dementia prevention; and 3) 136 participants, ages 65-85 years (young-old), also of the Portland area, enrolled in a study of the effects of yoga and exercise on cognition.Measurements: Data verified from labels, not from self-report.Results: Of the participants, 70.6% used dietary supplements. Women took supplements more often than men, and usage decreased with age. A greater percentage, 67.4%, of the non-metropolitan oldest-old took supplements, compared to 56.7% of the metropolitan oldest-old. The greatest usage, 89.7%, was in the metropolitan young-olds. All of these percentages exceed those for comparable age groups in national representative surveys.Conclusions: Dietary supplement usage by older adults in these studies in Oregon exceeded that in other reports and may reflect high interest in complementary and alternative medicine. This report confirms the results of other studies showing that elderly adults, particularly women, use dietary supplements more than other segments of the US population. Researchers and clinicians should be aware of this pattern and potential conflicts with research design or treatment regimen intended for older people. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS. However, it is unclear how p38 MAPK affects TDP-43 proteinopathy. Here, we show that p38α MAPK inhibition reduces pathological TDP-43 phosphorylation, aggregation, cytoplasmic mislocalization, and neurotoxicity. Remarkably, p38α MAPK inhibition mitigates aberrant TDP-43 phenotypes in diverse ALS patient-derived motor neurons. p38α MAPK phosphorylates TDP-43 at pathological S409/S410 and S292, which reduces TDP-43 liquid-liquid phase separation (LLPS) but allows pathological TDP-43 aggregation. Moreover, we establish that PRMT1 methylates TDP-43 at R293. Importantly, S292 phosphorylation reduces R293 methylation, and R293 methylation reduces S409/S410 phosphorylation. Notably, R293 methylation permits TDP-43 LLPS and reduces pathological TDP-43 aggregation. Thus, strategies to reduce p38α-mediated TDP-43 phosphorylation and promote PRMT1-mediated R293 methylation could have therapeutic utility for ALS and related TDP-43 proteinopathies., Competing Interests: Declaration of interests H.J.W., D.G.B., and N.J.B. were full-time employees and shareholders of AstraZeneca at the time these studies were conducted. S.J.M. is a consultant for SAGE Therapeutics and AstraZeneca, relationships that are regulated by Tufts University., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Life-space mobility can be a behavioral indicator of loneliness. This study examined the association between life-space mobility measured with motion sensors and weekly vs. annually reported loneliness., Methods: Participants were older adults who lived alone. Passive infrared motion sensors were placed in the bathroom, bedroom, kitchen, and living room. Time spent in each room and out-of-home across the day was derived and used as the measure of life-space mobility. Participants reported via weekly questionnaires whether they felt lonely. In annual visits, the UCLA loneliness scale was administered to a subsample (n = 71), and the scores were categorized into high, moderate, and low groups. We used generalized estimating equations (GEE) to correlate life-space mobility with weekly and yearly loneliness. Repeated observations from each individual were bootstrapped for 1000 rounds to associate annual and weekly loneliness measures., Results: We analyzed 4995 weeks of data from 139 participants (age = 78.1 ± 8.6, 74% female, 23% African Americans, 14% with MCI diagnosis). An additional hour in the bedroom in the afternoon was associated with a 21.4% increased odds (OR = 1.214, p = 0.049) of experiencing loneliness in the week. An additional hour out-of-home in the morning and in the afternoon was associated with 18.2% (OR = 0.818, p = 0.040) and 15.3% (OR = 0.847, p = 0.018) fewer odds of experiencing weekly loneliness. In the subsample with annual loneliness assessments, an additional hour out-of-home was associated with 38.1% (OR = 0.619, p = 0.006) fewer odds of being in the high UCLA loneliness group. Compared with the low UCLA group, those with high UCLA scores were five times more likely to report loneliness weekly (OR = 5.260, p = 0.0004)., Conclusions: Frequent and objective measurements of mobility combined with self-reported social wellbeing information can offer new insights into the experience of loneliness and provide opportunities for timely interventions., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Socially isolated individuals tend to have less access to cognitively stimulating activities, which could adversely impact their cognitive health. The Internet-Based Conversational Engagement Clinical Trial (I-CONECT) intervention was designed to deliver online conversation sessions to socially isolated older old adults to prevent cognitive decline. The current study examined the intervention efficacy on participants' weekly time spent out-of-home and their social interaction with family and friends., Methods: The intervention group engaged in frequent conversations with trained interviewers via the Internet. Both intervention and control group participants received 10-min weekly phone check-in calls over 48 weeks, during which they were asked to self-report their time (in hours) spent out of home and whether they had contacted family or friends during this week (yes/no). Linear mixed-effect models for repeated measures were run for time spent out-of-home, and mixed-effect models with a logistic link for contact with family and friends. The intervention effect was modeled by including an interaction term of time (measured in weeks) and group assignments (intervention vs. control). We ran subgroup analyses for participants with normal cognition (NC) and mild cognitive impairment (MCI). All models controlled for age, sex, race, education, and the historical event of COVID-19., Results: 5,495 weekly records were included in the analysis. The main effect of time was statistically significant ( p  < 0.001), suggesting participants spent more time out of home over time. Among the participants with NC, the intervention group had a steeper increase in their time spent out-of-home ( p  = 0.016) compared with the control group. Among the participants with MCI, the intervention group had an increased likelihood of contacting friends over time ( p  = 0.001) than the control group. The intervention effect on contact with family was not significant for either the NC or MCI group., Discussion: The I-CONECT intervention enhanced social activities among socially isolated older old participants, which could provide additional cognitive stimulation and prevent cognitive decline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Wu, Silbert, Kaye and Dodge.)

Background and Objectives: Social isolation is a risk factor for cognitive decline and dementia. We conducted a randomized controlled clinical trial (RCT) of enhanced social interactions, hypothesizing that conversational interactions can stimulate brain functions among socially isolated older adults without dementia. We report topline results of this multisite RCT (Internet-based conversational engagement clinical trial [I-CONECT]; NCT02871921)., Research Design and Methods: The experimental group received cognitively stimulating semistructured conversations with trained interviewers via internet/webcam 4 times per week for 6 months (induction) and twice per week for an additional 6 months (maintenance). The experimental and control groups both received weekly 10 minutes telephone check-ins. Protocol modifications were required due to the coronavirus disease 2019 pandemic., Results: A total of 186 participants were randomized. After the induction period, the experimental group had higher global cognitive test scores (Montreal Cognitive Assessment [primary outcome]; 1.75 points [p = .03]) compared with the control group. After induction, experimental group participants with normal cognition had higher language-based executive function (semantic fluency test [secondary outcome]; 2.56 points [p = .03]). At the end of the maintenance period, the experimental group of mild cognitive impairment subjects had higher encoding function (Craft Story immediate recall test [secondary outcome]; 2.19 points [p = .04]). Measure of emotional well-being improved in both control and experimental groups. Resting-state functional magnetic resonance imaging showed that the experimental group had increased connectivity within the dorsal attention network relative to the control group (p = .02), but the sample size was limited., Discussion and Implications: Providing frequent stimulating conversational interactions via the internet could be an effective home-based dementia risk-reduction strategy against social isolation and cognitive decline., Clinical Trials Registration Number: NCT02871921., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Translating high-confidence (hc) autism spectrum disorder (ASD) genes into viable treatment targets remains elusive. We constructed a foundational protein-protein interaction (PPI) network in HEK293T cells involving 100 hcASD risk genes, revealing over 1,800 PPIs (87% novel). Interactors, expressed in the human brain and enriched for ASD but not schizophrenia genetic risk, converged on protein complexes involved in neurogenesis, tubulin biology, transcriptional regulation, and chromatin modification. A PPI map of 54 patient-derived missense variants identified differential physical interactions, and we leveraged AlphaFold-Multimer predictions to prioritize direct PPIs and specific variants for interrogation in Xenopus tropicalis and human forebrain organoids. A mutation in the transcription factor FOXP1 led to reconfiguration of DNA binding sites and altered development of deep cortical layer neurons in forebrain organoids. This work offers new insights into molecular mechanisms underlying ASD and describes a powerful platform to develop and test therapeutic strategies for many genetically-defined conditions.

Purpose: To evaluate the positive predictive value (PPV) of an endometrial cancer case finding algorithm using International Classification of Disease 10th revision Clinical Modification (ICD-10-CM) diagnosis codes from US insurance claims for implementation in a planned post-marketing safety study. Two algorithm variants were evaluated., Methods: Provisional incident endometrial cancer cases were identified from 2016 through 2020 among women aged ≥50 years. One algorithm variant used diagnosis codes for malignant neoplasms of uterine sites (C54.x), excluding C54.2 (malignant neoplasm of myometrium); the other used only C54.1 (malignant neoplasm of endometrium). A random sample of medical records of recent incident provisional cases (2018-2020) was requested for adjudication. Confirmed cases showed biopsy evidence of endometrial cancer, documentation of cancer staging, or hysterectomy following diagnosis. We estimated the PPV of the variants with 95% confidence intervals (CI) excluding cases that had insufficient information., Results: Of 294 provisional cases adjudicated, 85% were from outpatient settings (n = 249). Mean age at diagnosis was 69.3 years. Among the 294 adjudicated cases (identified with the broader algorithm variant), the same 223 were confirmed endometrial cancer cases by both algorithm variants. The PPV (95% CI) for the broader algorithm variant was 84.2% (79.2% and 88.3%), and for the variant using only C54.1 was 85.8% (80.9% and 89.8%)., Conclusion: We developed and validated an algorithm using ICD-10-CM diagnosis codes to identify endometrial cancer cases in health insurance claims with a sufficiently high PPV to use in a planned post-marketing safety study., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: With the increasing utilization of medications worldwide, coupled with the increasing availability of long-term data, there is a growing opportunity and need for robust studies evaluating drug-cancer associations. One methodology of importance in such studies is the application of lag times., Methods: In this narrative review, we discuss the main reasons for using lag times., Results: Namely, we discuss the typically long latency period of cancer concerning both tumor promoter and initiator effects and outline why cancer latency is a key consideration when choosing a lag time. We also discuss how the use of lag times can help reduce protopathic and detection bias. Finally, we present practical advice for implementing lag periods., Conclusions: In general, we recommend that researchers consider the information that generated the hypothesis as well as clinical and biological knowledge to inform lag period selection. In addition, given that latency periods are usually unknown, we also advocate that researchers examine multiple lag periods in sensitivity analyses as well as duration analyses and flexible modeling approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer's Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6,728 African American, 8,899 Hispanic (HIS), and 3,232 East Asian individuals, performing within-ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. We identified 13 loci with cross-ancestry associations including known loci at/near CR1 , BIN1 , TREM2 , CD2AP , PTK2B , CLU , SHARPIN , MS4A6A , PICALM , ABCA7 , APOE and two novel loci not previously reported at 11p12 ( LRRC4C ) and 12q24.13 ( LHX5-AS1 ). Reflecting the power of diverse ancestry in GWAS, we observed the SHARPIN locus using 7.1% the sample size of the original discovering single-ancestry GWAS (n=788,989). We additionally identified three GWS ancestry-specific loci at/near ( PTPRK ( P =2.4×10 -8 ) and GRB14 ( P =1.7×10 -8 ) in HIS), and KIAA0825 ( P =2.9×10 -8 in NHW). Pathway analysis implicated multiple amyloid regulation pathways (strongest with P adjusted =1.6×10 -4 ) and the classical complement pathway ( P adjusted =1.3×10 -3 ). Genes at/near our novel loci have known roles in neuronal development ( LRRC4C, LHX5-AS1 , and PTPRK ) and insulin receptor activity regulation ( GRB14 ). These findings provide compelling support for using traditionally-underrepresented populations for gene discovery, even with smaller sample sizes.

Aging is a significant contributor to changes in sleep patterns, which has compounding consequences on cognitive health. A modifiable factor contributing to poor sleep is inadequate and/or mistimed light exposure. However, methods to reliably and continuously collect light levels long-term in the home, a necessity for informing clinical guidance, are not well established. We explored the feasibility and acceptability of remote deployment and the fidelity of long-term data collection for both light levels and sleep within participants' homes. The original TWLITE study utilized a whole-home tunable lighting system, while the current project is an observational study of the light environment already existing in the home. This was a longitudinal, observational, prospective pilot study involving light sensors remotely deployed in the homes of healthy adults ( n = 16, mean age: 71.7 years, standard deviation: 5.0 years) who were co-enrolled in the existing Collaborative Aging (in Place) Research Using Technology (CART) sub-study within the Oregon Center for Aging and Technology (ORCATECH). For 12 weeks, light levels were recorded via light sensors (ActiWatch Spectrum), nightly sleep metrics were recorded via mattress-based sensors, and daily activity was recorded via wrist-based actigraphy. Feasibility and acceptability outcomes indicated that participants found the equipment easy to use and unobtrusive. This proof-of-concept, feasibility/acceptability study provides evidence that light sensors can be remotely deployed to assess relationships between light exposure and sleep among older adults, paving the way for measurement of light levels in future studies examining lighting interventions to improve sleep.

Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack of well-curated lines from a large array of participants. Answer ALS has generated over 1,000 iPSC lines from control and amyotrophic lateral sclerosis (ALS) patients along with clinical and whole-genome sequencing data. The current report summarizes cell marker and gene expression in motor neuron cultures derived from 92 healthy control and 341 ALS participants using a 32-day differentiation protocol. This is the largest set of iPSCs to be differentiated into motor neurons, and characterization suggests that cell composition and sex are significant sources of variability that need to be carefully controlled for in future studies. These data are reported as a resource for the scientific community that will utilize Answer ALS data for disease modeling using a wider array of omics being made available for these samples., Competing Interests: Declaration of interests US patent 10,221,395-B2 has been granted describing a method for reprogramming blood to induced pluripotent stem cells. Apart from this issued patent filing, the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To describe real-world testing patterns for RET in US patients with advanced/metastatic medullary thyroid cancer and determine consistency of real-world testing practices with national guidelines. Materials & methods: The authors performed a retrospective medical record analysis of patients with advanced/metastatic medullary thyroid cancer who initiated systemic therapy between 2013 and 2018. Seventy-five US-based oncologists collected the data using a customized electronic data collection form. Results: A total of 59.6% (121 of 203) of patients underwent testing for RET , and 37.2% (45 of 121) had a RET mutation, of which 55.6% were identified as RET mutation-positive before initial diagnosis. Overall, 90 (44.3%) patients were tested for biomarkers on or after initial diagnosis, with RET being the most tested (95.6%) biomarker. Conclusion: The authors' findings suggest an opportunity to improve testing rates in accordance with treatment guidelines.

Enteroendocrine cells are specialized sensory cells of the gut-brain axis that are sparsely distributed along the intestinal epithelium. The functions of enteroendocrine cells have classically been inferred by the gut hormones they release. However, individual enteroendocrine cells typically produce multiple, sometimes apparently opposing, gut hormones in combination, and some gut hormones are also produced elsewhere in the body. Here, we developed approaches involving intersectional genetics to enable selective access to enteroendocrine cells in vivo in mice. We targeted FlpO expression to the endogenous Villin1 locus (in Vil1-p2a-FlpO knock-in mice) to restrict reporter expression to intestinal epithelium. Combined use of Cre and Flp alleles effectively targeted major transcriptome-defined enteroendocrine cell lineages that produce serotonin, glucagon-like peptide 1, cholecystokinin, somatostatin, or glucose-dependent insulinotropic polypeptide. Chemogenetic activation of different enteroendocrine cell types variably impacted feeding behavior and gut motility. Defining the physiological roles of different enteroendocrine cell types provides an essential framework for understanding sensory biology of the intestine., Competing Interests: MH, JK, ED, NJ, FR No competing interests declared, FG Is a consultant for Kallyope, Inc, SL Reviewing editor, eLife, (© 2023, Hayashi et al.)

Postmortem (PM) magnetic resonance imaging (MRI) can serve as a bridge between in vivo imaging and histology by connecting MRI observed macrostructural findings to histological staining and microstructural changes. Data were acquired from 20 formalin-fixed brains including T2, T1, PD, and T2*-weighted images of left hemispheres and 6-mm-thick coronal slices. Tissue slices were bisected, aligned to MR images and used to guide histological sampling. Markers of myelin and oligodendroglia alterations were semiquantitatively rated and compared within white matter hyperintensities (WMHs) and normal-appearing white matter. Tissue priors were created from 3T in vivo data and used to guide segmentation of WMH. PM WMH and hemisphere volumes were compared to volumes derived from in vivo data. PM T2 WMH and T1 hemisphere volumes were correlated with in vivo 3T FLAIR WMH and T1 hemisphere volumes. WMH showed significant myelin loss, decreased GFAP expression and increased vimentin expression. MR-visible perivascular spaces and cortical microvascular lesions were successfully captured on histopathological sections. PM MRI can quantify cerebrovascular disease burden and guide tissue sampling, allowing for more comprehensive characterization of cerebrovascular disease that may be used to study etiologies of age-related cognitive change., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)

Introduction: Examining the emotional functioning of individuals with mild cognitive impairment (MCI) could help describe their cognitive status and inform the development of interventions. This study compared the emotional characteristics of socially isolated older adults with and without MCI., Methods: We used baseline data from the Internet-based Conversational Engagement Clinical Trial. Emotional characteristics were assessed with the National Institutes of Health Toolbox Emotion Battery (NIHTB-EB). MCI status was determined with a consensus clinical diagnosis., Results: This study included 163 participants (mean age = 81.2 years, non-Hispanic Black = 20.7%, MCI = 52.8%). MCI was associated with higher negative affect and lower psychological well-being. Non-Hispanic Black participants scored lower in sadness, higher in positive affect, and higher in meaning and purpose than non-Hispanic White participants., Conclusion: Older adults with MCI experience more negative emotions and worse psychological well-being than those with normal cognition. The NIHTB-EB appears to be a sensitive tool to detect emotional characteristics associated with cognitive decline., Competing Interests: The authors have no conflicts of interest to disclose. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: Supporting the psychological needs of the patient during Anterior Cruciate Ligament Reconstruction (ACLR) rehabilitation is of paramount importance in order to optimize function and return to sport. Despite this, the amount of psychological training physiotherapists receive is inadequate., Purpose: the central aim of this study was to gain valuable insight, through the lens of the student physiotherapist, in relation to biopsychosocial practices used within ACL rehabilitation., Method: A phenomenological design using an inductive approach through purposive sampling was used. The study conducted semi-structured interviews, which involved ten undergraduate and postgraduate physiotherapy students from a UK University institution. The study identified perceptions, experiences and training surrounding a biopsychosocial approach within ACL rehabilitation. Data analysis included thematic analysis with triangulation and an audit trail to enhance confirmability and credibility., Results: Participants demonstrated a superficial understanding of the biopsychosocial approach, psychological symptoms and the significance of applying a patient-centered approach. Nonetheless, participants consistently reported barriers to implementing this approach, including the application of theory to practice when working with patients following ACL surgery., Discussion: Findings were consistent with previous research surrounding inadequate biopsychosocial education and training within ACL rehabilitation. The application of theory of the model to clinical practice was absent from the students' training., Conclusion: These findings suggest that student physiotherapists are aware of the possible benefits of incorporating psychological interventions but feel inadequately trained, highlighting a need for a review of the curriculum. Future research focusing on pedagogy-based strategies to effectively equip students to apply biopsychosocial theory to practice is of critical importance to prepare students for contemporary ACL rehabilitation and practice.