Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme

Background: People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. Methods: The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer’s disease, vascular dementia, mixed Alzheimer’s and vascular dementia, Parkinson’s disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer’s Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. Results: The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson’s disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (− 0.15 points per year). Informant-rated scores declined over time (− 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (− 2.18 points per year). Conclusions: Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson’s disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups

A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road

Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes

Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme

\ua9 The Author(s) 2024.Background: People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. Methods: The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer’s disease, vascular dementia, mixed Alzheimer’s and vascular dementia, Parkinson’s disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer’s Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. Results: The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson’s disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (− 0.15 points per year). Informant-rated scores declined over time (− 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (− 2.18 points per year). Conclusions: Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson’s disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups

High sample throughput genotyping for estimating C-lineage introgression in the dark honeybee: an accurate and cost-effective SNP-based tool

The natural distribution of the honeybee (Apis mellifera L.) has been changed by humans in recent decades to such an extent that the formerly widest-spread European subspecies, Apis mellifera mellifera, is threatened by extinction through introgression from highly divergent commercial strains in large tracts of its range. Conservation efforts for A. m. mellifera are underway in multiple European countries requiring reliable and cost-efficient molecular tools to identify purebred colonies. Here, we developed four ancestry-informative SNP assays for high sample throughput genotyping using the iPLEX Mass Array system. Our customized assays were tested on DNA from individual and pooled, haploid and diploid honeybee samples extracted from different tissues using a diverse range of protocols. The assays had a high genotyping success rate and yielded accurate genotypes. Performance assessed against whole-genome data showed that individual assays behaved well, although the most accurate introgression estimates were obtained for the four assays combined (117 SNPs). The best compromise between accuracy and genotyping costs was achieved when combining two assays (62 SNPs). We provide a ready-to-use cost-effective tool for accurate molecular identification and estimation oinfo:eu-repo/semantics/publishedVersio

Psychological predictors of 'living well' with dementia: findings from the IDEAL study.

OBJECTIVES:Increasingly, research has explored how psychological resources enable adaptation to illness. However, it is unclear whether psychological resources protect against the potential negative effects on living well with a progressive and life-limiting condition such as dementia. This paper examines the association between psychological resources and the ability to 'live well' with dementia. METHOD:Data from 1547 people with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort were used. Multivariate linear regression was employed to examine the association between self-reported measures of psychological resources (self-efficacy, optimism and self-esteem) and indices of capability to 'live well' (quality of life, well-being and life satisfaction). RESULTS:All three measures of psychological resources had positive and independent associations with indices of living well and the effect sizes were similar. Effect sizes reduced when accounting for shared variance between psychological resources, showing some overlap in these constructs. CONCLUSION:Self-efficacy, optimism and self-esteem were each associated with capability to 'live well'. Overlap between these three resources is evident and when combined they may provide greater resilience when dealing with the challenges of living with dementia. Interventions for people with dementia could seek to improve levels of these potentially-modifiable psychological resources.Economic and Social Research Council (UK) and the National Institute for Health Research (UK

Spared unconscious influences of spatial memory in diencephalic amnesia

Spatial memory is crucial to our daily lives and in part strongly depends on automatic, implicit memory processes. This study investigates the neurocognitive basis of conscious and unconscious influences of object–location memory in amnesic patients with Korsakoff’s syndrome (N = 23) and healthy controls (N = 18) using a process-dissociation procedure in a computerized spatial memory task. As expected, the patients performed substantially worse on the conscious memory measures but showed even slightly stronger effects of unconscious influences than the controls. Moreover, a delayed test administered after 1 week revealed a strong decline in conscious influences in the patients, while unconscious influences were not affected. The presented results suggest that conscious and unconscious influences of spatial memory can be clearly dissociated in Korsakoff’s syndrome

The impact of comorbidity on the quality of life of people with dementia: findings from the IDEAL study.

Background:The aim was to investigate the comorbidity profile of people with dementia and examine the associations between severity of comorbidity, health-related quality of life (HRQoL) and quality of life (QoL). Methods:The improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort consisted of 1,547 people diagnosed with dementia who provided information on the number and type of comorbid conditions. Participants also provided ratings of their health-related and dementia-specific QoL. Results:The majority of the sample were living with more than one chronic condition. Hypertension was commonly reported and frequently combined with connective tissue disease, diabetes and depression. The number of comorbid conditions was associated with low QoL scores, and those with severe comorbidity (≥5 conditions) showed the greatest impact on their well-being. Conclusions:Comorbidity is an important risk factor for poor QoL and health status in people with dementia. Greater recognition of the nature and impact of comorbidity is needed to inform support and interventions for people with dementia and a multidisciplinary approach to care provision is recommended.Economic and Social Research Council (UK) and the National Institute for Health Research (UK

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: IDEAL data were deposited with the UK data archive in April 2020. Details of how to access the data can be found here: https://reshare.ukdataservice.ac.uk/854293/Background People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. Methods The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer’s disease, vascular dementia, mixed Alzheimer’s and vascular dementia, Parkinson’s disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer’s Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. Results The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson’s disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (− 0.15 points per year). Informant-rated scores declined over time (− 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (− 2.18 points per year). Conclusions Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson’s disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups.Economic and Social Research Council (ESRC)National Institute for Health and Care Research (NIHR)Alzheimer’s Societ