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Mild cognitive impairment with Lewy bodies (MCI-LB) may be identified prospectively based on the presence of cognitive impairment and several core clinical features (visual hallucinations, cognitive fluctuations, parkinsonism, and REM sleep behavior disorder). MCI-LB may vary in its presenting features, which may reflect differences in underlying pathological pattern, severity, or comorbidity.
We aimed to assess how clinical features of MCI-LB accumulate over time, and whether this is associated with the rate of cognitive decline.
Methods
In this cohort study, 74 individuals seen with MCI-LB prospectively underwent repeated annual cognitive and clinical assessment up to nine years. Relationships between clinical features (number of core features present and specific features present) and cognitive change on the Addenbrooke’s Cognitive Examination–Revised (ACE-R) were examined with time-varying mixed models. The accumulation of core clinical features over time was examined with a multi-state Markov model.
Results
When an individual with MCI-LB endorsed more clinical features, they typically experienced a faster cognitive decline (ACE-R Score Difference β = −1.1 [−1.7 to −0.5]), specifically when experiencing visual hallucinations (β = −2.1 [−3.5 to −0.8]) or cognitive fluctuations (β = −3.4 [−4.8 to −2.1]).
Individuals with MCI-LB typically acquired more clinical features with the passage of time (25.5% [20.0–32.0%] one-year probability), limiting the prognostic utility of baseline-only features.
Conclusions
The clinical presentation of MCI-LB may evolve over time. The accumulation of more clinical features of Lewy body disease, in particular visual hallucinations and cognitive fluctuations, may be associated with a worse prognosis in clinical settings.
Recent research highlights the dynamics of suicide risk, resulting in a shift toward real-time methodologies, such as ecological momentary assessment (EMA), to improve suicide risk identification. However, EMA’s reliance on active self-reporting introduces challenges, including participant burden and reduced response rates during crises. This study explores the potential of Screenomics—a passive digital phenotyping method that captures intensive, real-time smartphone screenshots—to detect suicide risk through text-based analysis.
Method
Seventy-nine participants with past-month suicidal ideation or behavior completed daily EMA prompts and provided smartphone data over 28 days, resulting in approximately 7.5 million screenshots. Text from screenshots was analyzed using a validated dictionary encompassing suicide-related and general risk language.
Results
Results indicated significant associations between passive and active suicidal ideation and suicide planning with specific language patterns. Detection of words related to suicidal thoughts and general risk-related words strongly correlated with self-reported suicide risk, with distinct between- and within-person effects highlighting the dynamic nature of suicide risk factors.
Conclusions
This study demonstrates the feasibility of leveraging smartphone text data for real-time suicide risk detection, offering a scalable, low-burden alternative to traditional methods. Findings suggest that dynamic, individualized monitoring via passive data collection could enhance suicide prevention efforts by enabling timely, tailored interventions. Future research should refine language models and explore diverse populations to extend the generalizability of this innovative approach.
The aim of this study was to determine whether there was a significant change in cardiac [123I]-metaiodobenzylguanidine uptake between baseline and follow-up in individuals with mild cognitive impairment with Lewy bodies (MCI-LB) who had normal baseline scans. Eight participants with a diagnosis of probable MCI-LB and a normal baseline scan consented to a follow-up scan between 2 and 4 years after baseline. All eight repeat scans remained normal; however, in three cases uptake decreased by more than 10%. The mean change in uptake between baseline and repeat was −5.2% (range: −23.8% to +7.0%). The interpolated mean annual change in uptake was −1.6%.
We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.
To implement and evaluate a point-of-care (POC) molecular testing platform for respiratory viruses in congregate living settings (CLS).
Design:
Prospective quality improvement study.
Setting:
Seven CLS, including three nursing homes and four independent-living facilities.
Participants:
Residents of CLS.
Methods:
A POC platform for COVID-19, influenza A and B, and respiratory syncytial virus was implemented at participating CLS from December 1, 2022 to April 15, 2023. Residents with respiratory symptoms underwent paired testing, with respiratory specimens tested first with the POC platform and then delivered to an off-site laboratory for multiplex respiratory virus panel (MRVP) polymerase chain reaction (PCR) as per standard protocol. Turn-around time and diagnostic accuracy of the POC platform were compared against MRVP PCR. In an exploratory analysis, time to outbreak declaration among participating CLS was compared against a convenience sample of 19 CLS that did not use the POC platform.
Results:
A total of 290 specimens that underwent paired testing were included. Turn-around time to result was significantly shorter with the POC platform compared to MRVP PCR, with median difference of 36.2 hours (interquartile range 21.8–46.4 hours). The POC platform had excellent diagnostic accuracy compared to MRVP PCR, with area under the curve statistic of .96. Time to outbreak declaration was shorter in CLS that used the POC platform compared to CLS that did not.
Conclusion:
Rapid POC testing platforms for respiratory viruses can be implemented in CLS, with high diagnostic accuracy, expedited turn-around times, and shorter time to outbreak declaration.
Most evidence supporting screening for undernutrition is for children aged 6–59 months. However, the highest risk of mortality and highest incidence of wasting occurs in the first 6 months of life. We evaluated relationships between neonatal anthropometric indicators, including birth weight, weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ) and mid-upper arm circumference (MUAC) and mortality and growth at 6 months of age among infants in Burkina Faso.
Design:
Data arose from a randomised controlled trial evaluating neonatal azithromycin administration for the prevention of child mortality. We evaluated relationships between baseline anthropometric measures and mortality, wasting (WLZ < –2), stunting (LAZ < –2) and underweight (WAZ < –2) at 6 months of age were estimated using logistic regression models adjusted for the child’s age and sex.
Setting:
Five regions of Burkina Faso.
Participants:
Infants aged 8–27 d followed until 6 months of age.
Results:
Of 21 832 infants enrolled in the trial, 7·9 % were low birth weight (<2500 g), 13·3 % were wasted, 7·7 % were stunted and 7·4 % were underweight at enrolment. All anthropometric deficits were associated with mortality by 6 months of age, with WAZ the strongest predictor (WAZ < –2 to ≥ –3 at enrolment v. WAZ ≥ –2: adjusted OR, 3·91, 95 % CI, 2·21, 6·56). Low WAZ was also associated with wasting, stunting, and underweight at 6 months.
Conclusions:
Interventions for identifying infants at highest risk of mortality and growth failure should consider WAZ as part of their screening protocol.
Older adults residing in congregate living settings (CLS) such as nursing homes and independent living facilities remain at increased risk of morbidity and mortality from coronavirus disease 2019. We performed a prospective multicenter study of consecutive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) exposures to identify predictors of transmission in this setting.
Methods:
Consecutive resident SARS-CoV-2 exposures across 17 CLS were prospectively characterized from 1 September 2022 to 1 March 2023, including factors related to environment, source, and exposed resident. Room size, humidity, and ventilation were measured in locations where exposures occurred. Predictors were incorporated in a generalized estimating equation model adjusting for the correlation within CLS.
Results:
Among 670 consecutive exposures to SARS-CoV-2 across 17 CLS, transmission occurred among 328 (49.0%). Increased risk was associated with nursing homes (odds ratio (OR) = 90.8; 95% CI, 7.8–1047.4), Jack and Jill rooms (OR = 2.2; 95% CI, 1.3–3.6), from source who was pre-symptomatic (OR = 11.2; 95% CI, 4.1–30.9), symptomatic (OR = 6.5; 95% CI, 1.4–29.9), or rapid antigen test positive (OR = 35.6; 95% CI, 5.6–225.6), and in the presence of secondary exposure (OR = 6.3; 95% CI, 1.6–24.0). Exposure in dining room was associated with reduced risk (OR = 0.02; 95% CI, 0.005–0.08) as was medium room size (OR = 0.3; 95% CI, 0.2–0.6). Recent vaccination of exposed resident (OR = 0.5; 95% CI, 0.3–1.0) and increased ventilation of room (OR = 0.9; 95% CI, 0.8–1.0) were marginally associated with reduced risk.
Conclusion:
Prospective assessment of SARS-CoV-2 exposures in CLS suggests that source characteristics and location of exposure are most predictive of resident transmission. These findings can inform risk assessment and further opportunities to prevent transmission in CLS.
We evaluated whether universal chlorhexidine bathing (decolonization) with or without COVID-19 intensive training impacted COVID-19 rates in 63 nursing homes (NHs) during the 2020–2021 Fall/Winter surge. Decolonization was associated with a 43% lesser rise in staff case-rates (P < .001) and a 52% lesser rise in resident case-rates (P < .001) versus control.
We conducted a tabletop exercise on influenza outbreak preparedness that engaged a large group of congregate living settings (CLS), with improvements in self-reported knowledge and readiness. This proactive approach to responding to communicable disease threats has potential to build infection prevention and control capacity beyond COVID-19 in the CLS sector.
Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer’s disease (MCI-AD), and any performance deficits which emerged with sustained effort.
Method:
We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years).
Results:
While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1–4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3–2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2–8.8).
Conclusions:
Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.
Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.
Methods
Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.
Results
Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).
Conclusion
Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.
Evidence suggests that both childhood trauma and perceived stress are risk factors for the development of psychosis, as well as negative symptoms such as anhedonia. Previous findings link increases in perceived stress to anhedonia in individuals at clinical high risk for psychosis (CHR) and depression; however, the role of childhood trauma in this relationship has not yet been explored, despite consistent evidence that it is associated with sensitisation to later stress.
Aims
To examine whether perceived stress mediates the relationship between childhood trauma and anhedonia in a group of youth at CHR as well as in controls (groups with depression and with no diagnosed mental health concerns).
Method
The study used multigroup mediation to examine the indirect effects of childhood trauma on anhedonia via perceived stress in CHR (n = 117) and depression groups (n = 284) and non-psychiatric controls (n = 124).
Results
Perceived stress mediated the relationship between childhood trauma and consummatory anhedonia regardless of group status. Perceived stress mediated the relationship between childhood trauma and anticipatory anhedonia for the CHR and depression groups, but not for non-psychiatric controls. Further, groups differed in the magnitude of this relationship, with the effects trending towards stronger for those in the CHR group.
Conclusions
Our findings suggest a potential transdiagnostic pathway through which childhood trauma contributes to anhedonia across severe mental illness.
To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Design:
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Setting:
Community settings and care homes in 26 UK centers.
Participants:
People with probable or possible Alzheimer’s disease and agitation.
Measurements:
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
Results:
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
Conclusions:
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
OBJECTIVES/GOALS: Our concept of reciprocal innovation (RI) supports global health (GH) research partnerships that address shared health challenges for mutual benefit in both high and low- and middle-income (LMIC) settings. To advance this GH approach, the Indiana CTSI launched a RI program building on longstanding global health partnerships in East Africa METHODS/STUDY POPULATION: A core component of the program is annual RI workshops to promote reciprocal approaches in GH, identify priority areas for reciprocal research, and link investigators and stakeholders across settings. The first meeting in 2019 was in-person and focused on identifying health priority areas from the perspective of Indiana stakeholders. The second meeting was held virtually and focused on priority areas in East Africa. The third meeting focused on shared priority areas and discussing potential RI research projects. Agenda sessions include (1) presenting successful examples of funded RI projects; (2) breakout groups to share proposal ideas in preparation for the RI grants program; (3) building partnerships with colleagues in similar fields RESULTS/ANTICIPATED RESULTS: As of 2021, three RI workshops have been held with an average of 60 attendees at each workshop. Participants identified several overlapping priority areas for research and RI in Indiana and East Africa, including research in chronic disease, substance abuse, infant and maternal health, and access to healthcare. A Global Health Innovation Exchange of RI projects was created to support connections between locally- and globally-focused investigators. The repository is used to share updates on project progress, outcomes, and published materials. Workshops have also been used to explore a reciprocal innovation virtual platform to facilitate and foster more regular collaborations between globally and locally-focused investigators and pursue research projects on shared health challenges for mutual benefit DISCUSSION/SIGNIFICANCE: The collaboration at the stakeholder meetings set the foundation for continued partnership building, strong proposals for RI grants, and dissemination and translation of successful RI projects. To leverage momentum from the meetings, we are building a virtual RI platform to connect PIs across multiple CTSAs and increase the footprint of RI efforts
Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC).
Design:
Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC.
Setting:
Participants were recruited from Memory Services in the North East of England.
Participants:
Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.
Measurements:
Olfaction was assessed using SS-16 and a questionnaire.
Results:
Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them.
Conclusions:
MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.
The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed).
Method:
Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer’s disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall.
Results:
MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p = .03, g = .45; Digit Symbol Substitution Test (DSST): p = .04, g = .47; DSST Error Check: p < .001, g = .68] and executive function [Trail Making Test Ratio (A/B): p = .04, g = .52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p = .01, g = .46) and verbal (Rey Auditory Verbal Learning Test: p = .04, g = .42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps > .05)
Conclusions:
MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.
Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer’s disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel.
Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01–3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$11–18 arcsec, resulting in a catalogue of $\sim$220 000 sources, of which $\sim$180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.