False memory and delusions in Alzheimer's disease

Aims: This thesis aimed to investigate the relationship between memory errors and delusions in Alzheimer’s disease (AD), in order to further elucidate the mechanisms underlying delusion formation. This was achieved by undertaking narrative and systematic review of relevant literature, by exploring the relationship between performance on memory and metamemory tasks and delusions in AD patient populations and by investigating the neuroanatomical correlates of memory errors and delusions in AD patient populations. // Methods: I recruited 27 participants with and without delusions in AD and compared performance on measures of context memory, false memory and metamemory. I explored statistically significant behavioural findings further in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort of participants with AD (n = 733). I then conducted hypothesis-driven region of interest and exploratory voxel-based morphometric analyses to determine the relationship between false memory and delusions and regional brain volume in the ADNI cohort. This informed similar analyses of neuroimaging data in my own participants (n = 8). // Results: In both samples, individuals with delusions in AD had higher false recognition rates on recognition memory tasks than those without delusions. False recognition was inversely correlated with volume of medial temporal lobe, ventral visual stream and prefrontal cortex in both samples. In the ADNI sample, false recognition was also inversely correlated with anterior cingulate cortex (ACC) volume bilaterally. Participants with delusions had reduced volume of right ACC and increased volume of right parahippocampal gyrus compared to the control group. // Conclusions: These two complementary studies provide evidence of specific memory impairments associated with both delusions and a distinct pattern of brain atrophy in AD. Simple cognitive interventions can reduce false recognition rates in AD. Given the significant risks associated with antipsychotic drug treatment of delusions, exploring how these non-pharmacological interventions potentially affect psychosis symptoms in AD is an important next step

Misidentification subtype of alzheimer's disease psychosis predicts a faster cognitive decline

The presence of psychosis is associated with more rapid decline in Alzheimer's disease (AD), but the impact of paranoid (persecutory delusions) and misidentification (misperceptions and/or hallucinations) subtypes of psychosis on the speed of decline in AD is still unclear. Here we analysed data on Alzheimer's Disease Neuroimaging Initiative (ADNI)2 participants with late mild cognitive impairment or AD and we described individual trajectories of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) scores using a semi-mechanistic, logistic model, with a mixed effects based approach, which accounted for drop-out, and adjusted for baseline Mini Mental State Examination scores. The covariate model included psychosis subtypes, age, gender, education, medications and Apo-e ε4 genotype. We found that ADAS-cog rate of increase was doubled in misidentification (βr,misid_subtype =0.63, p=0.031) and mixed (both subtypes) ((βr,mixed_subtype =0.70, p=0.003) compared to non-psychotic (or paranoid) subjects suggesting that the misidentification subtype may represent a distinct AD sub-phenotype associated with an accelerated pathological process. This article is protected by copyright. All rights reserved

High-throughput evaluation of organic contaminant removal efficiency in a wastewater treatment plant using direct injection UHPLC-Orbitrap-MS/MS

Removal efficiency can be estimated from non-target data using the ratio of peak areas in effluent and influent

Association Between False Memories and Delusions in Alzheimer Disease

IMPORTANCE: Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories. OBJECTIVE: To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions. DESIGN, SETTING, AND PARTICIPANTS: Since the Alzheimer's Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021. EXPOSURE: Enrollment in the ADNI. MAIN OUTCOMES AND MEASURES: The main outcomes included false recognition, measured with the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions. RESULTS: Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P < .001), right hippocampal volume (0.94 [0.92-0.97], P < .001), left entorhinal cortex volume (0.94 [0.91-0.97], P < .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P < .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P < .001). There was no overlap between locations associated with false recognition and those associated with delusions. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis

Feasibility and outcomes of Fibreoptic Endoscopic Evaluation of Swallowing following prophylactic swallowing rehabilitation in head and neck cancer

Objectives Investigate the feasibility and outcomes of fibreoptic endoscopic evaluation of swallowing (FEES) following a programme of prophylactic swallowing exercises in head and neck cancer (HNC) patients treated with radiotherapy. Design Prospective, single cohort, feasibility study. Setting Three head and neck cancer centres in Scotland. Participants Pre‐radiotherapy HNC patients who consented to participate in a prophylactic swallowing intervention. Outcome measures FEES recruitment and retention rates, assessment acceptability and compliance, qualitative process evaluation. Results Higher rates of recruitment and retention were achieved in centres where FEES equipment was available on site. Travel and anticipated discomfort were barriers to recruitment. Data completion was high for all rating scales, with goo d reliability. Following radiotherapy, swallowing safety significantly deteriorated for liquid boluses (p=0.005‐0.03); pharyngeal residue increased for liquid and semi‐solid boluses. Pharyngo‐laryngeal oedema was present pre‐treatment and significantly increased post‐radiotherapy (p=0.001). Patients generally reported positive experience of FEES for their own learning and establishing a baseline. Conclusions FEES is an acceptable method of assessing patients for a prophylactic swallowing intervention and offers some additional information missing from VF. Barriers have been identified and should be taken into account in order to maximise recruitment for future trials

The UK Longitudinal Linkage Collaboration: A trusted research environment for the longitudinal research community

Objectives Our Trusted Research Environment (TRE) provides a centralised infrastructure to pool Longitudinal Population Studies’ (LPS) data and systematically link participants’ routine health, administrative and environmental records. All data are held in a centralised research resource which is now certified by UK Statistics Authority as meeting the Digital Economy Act standard. Approach We have created an unprecedented infrastructure integrating data from interdisciplinary and pan-UK LPS linked to participants’ NHS England records with delegated access responsibilities. Integrated and curated data are made available for pooled analysis within a functionally anonymous DEA and ISO 27001 accredited TRE. We developed a bespoke governance and data curation framework with LPS data managers and Public/participant contributors. New data pipelines are being built with partners at ADRUK and the Office of National Statistics to link non-health records. Our design supports long-term sustainability, linkage accuracy and the ability to link data at both an individual and household level. Results This organisation is a collaboration of >24 LPS with ~280,000 participants. Participants' data are linked to NHS records and geo-coded environmental exposures. This resource is now accessible for public benefit research for bona fide UK researchers. Administrative data including tax, work and pensions, and education are being added to the resource. This data flow is enabled by: (1) a model where TTP processes participant identifiers for many different data owners; (2) creation of a novel longitudinal data pipeline, enabling linkage, data extraction and update of records over time; (3) an access framework where Linked Data Access Panel considers applications on behalf of data owners (e.g., the NHS), with review by a Public Panel and distributing applications to LPS for approval of appropriate data use. Conclusion Our organisation provides a strategic research-ready platform for longitudinal research. We are extending linkages of LPS participants to previously inaccessible datasets. The research resource is positioned to allow researchers to investigate cross-cutting themes such as understanding health and social inequalities, health-social-environmental interactions, and managing the COVID-19 recovery

UK Longitudinal Linkage Collaboration – and the challenges in creating a new Longitudinal Populations Studies linked data resource.

Objectives The UK Longitudinal Linkage Collaboration (UK LLC) is a new, unprecedented infrastructure enabling research into the COVID-19 pandemic. The UK LLC integrates data from >20 UK longitudinal studies with systematically linked health, administrative and environmental records to facilitate cross-disciplinary COVID-19 research for accredited UK based researchers. Approach Bringing together all of the key components that form the UK LLC was a huge challenge that may have only been possible in the midst of the pandemic. First, we collaborated with the Longitudinal Population Studies (LPS) to create and agree how data linkage, data provision and applications to access the UK LLC would work. In parallel, public contributors helped to create fair processing materials. Finally, we worked closely with NHS Digital and other key national data providers to organise approvals for all studies to be linked, and for the UK LLC to have delegated decision-making for research applications. Results We faced a myriad of challenges creating the UK LLC including: • Short timeframe and short-term funding structure – initial funding for six months with an 18-month extension. • Working across >20 different LPS and four nations with different structures for access, consent and data provision. • Lack of capacity at various points in the data pipeline due to the volume of COVID-19 research required and underway across the involved organisations. • Data processing complexities – split data method means no one can see the entire process therefore catching linkage errors requires working across four different organisations. • With such complex data flows it is challenging to find the balance with communications about data to the public – being accurate about what we are doing, but expressing the complexity in lay terms. Conclusion Creating the UK LLC required collaboration with LPS, data providers and researchers. An iterative approach to creating the data application and data provision pipelines was crucial in developing these processes. The UK LLC was built quickly, from initial funding in October 2020 to provisioning data to researchers in December 2021

A Nursery-Based Cooking Skills Programme with Parents and Children Reduced Food Fussiness and Increased Willingness to Try Vegetables: A Quasi-Experimental Study

Children’s fussy eating is associated with a reduced vegetable intake. This quasi-experimental study evaluated “Big Chef Little Chef” (BCLC), a nursery-based cooking skills programme aimed at reducing food fussiness and increasing willingness to try green vegetables by incorporating repeated exposure and sensory learning. Parent and child (3–5 years) dyads attended BCLC for four/1.5 h weekly sessions. A comparison group was recruited after BCLC completion and attended a single education session at week 1. A questionnaire measured food fussiness at week 1 and week 4. At week 4, all children were offered six green vegetables (raw and cooked) and an average score (1 = did not try; 2 = tried it/ate some; 3 = ate it all) was calculated for willingness to try vegetables. In total, 121 dyads (intervention: n = 64; comparison: n = 57) participated. The food fussiness score (1 min–5 max) in the intervention group decreased significantly from 3.0 to 2.6 (p < 0.01) between time points, while there was no change in the comparison group (3.1 (week 1) and 3.0 (week 4)). The intervention group was more willing to try green vegetables with significantly higher (p < 0.001) median scores for raw and cooked vegetables (2.5 for both) compared with the comparison group (2.0 and 1.7, respectively). The BCLC reduced food fussiness and increased willingness to try green vegetables

Genome-Wide Association Study of Peripheral Artery Disease

Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status. Results: We identified 5 genome-wide significant (P-associationPeer reviewe