Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
655
result(s) for
"Darby, David"
Sort by:
Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal
P
-threshold (
P
optimal
) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.
Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.
Journal Article
Edward Hopper's New York
\"A revealing exploration of Edward Hopper's inspired relationship to New York City through his paintings, drawings, prints, and never-before-published archival materials This engaging book delves into the iconic relationship between Edward Hopper (1882-1967) and New York City. This comprehensive look at an essential aspect of the revered American artist's life reveals how Hopper's experience of New York's spaces, sensations, and architecture shaped his vision and served as a backdrop for his distillations of the urban experience. During sidewalk strolls and elevated train rides, Hopper sketched the city's many windowed facades. Exterior views gave way to interior lives, forging one of Hopper's defining preoccupations: the convergence of public and private. These permeable walls allowed Hopper to evoke the perplexing awareness of being alone in a crowd that is synonymous with modern urban life. Drawing on the vast resources of the Whitney Museum of American Art, the largest repository of Hopper's work, and the recently acquired gift of the Sanborn Hopper Archive, this book features more than 300 illustrations and fresh insight from authoritative and emerging scholars\"-- Provided by publisher.
BOOK
Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech
Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and neuroimaging data described in studies of FTD and PPA were systematically reviewed. A meta-analysis was conducted for speech measures that were used consistently in multiple studies. Results: The methods and nomenclature used to describe speech in these disorders varied between studies. Our meta-analysis identified 3 speech measures which differentiate variants or healthy control-group participants (e.g., nonfluent and logopenic variants of PPA from all other groups, behavioral-variant FTD from a control group). Deficits within the frontal-lobe speech networks are linked to motor speech profiles of the nonfluent variant of PPA and progressive apraxia of speech. Motor speech impairment is rarely reported in semantic and logopenic variants of PPA. Limited data are available on motor speech impairment in the behavioral variant of FTD. Conclusions: Our review identified several measures of speech which may assist with diagnosis and classification, and consolidated the brain-behavior associations relating to speech in FTD, PPA, and progressive apraxia of speech.
Journal Article
Deep phenotyping of socio-emotional skills in children with typical development, neurodevelopmental disorders, and mental health conditions: Evidence from the PEERS
Socio-emotional skills, including social competence and social cognition, form the basis for robust relationships and wellbeing. Despite their importance, these skills are poorly defined and measured, particularly in children with developmental vulnerabilities. As a consequence, targets for effective management and treatment remain unclear. We aimed to i) phenotype social competence and social cognition in typically developing children (TDC) and in children with neurodevelopmental or mental health disorders (clinical groups) and ii) establish the relationships between these child-direct measures and parent ratings of social competence and behavior. Using a multi-site, cross-sectional study design, we recruited 513 TDC and 136 children with neurodevelopmental (autism spectrum disorder [ASD], attention deficit hyperactivity disorder [ADHD]) or mental health (Anxiety Disorder [ANX]) diagnoses (age range 5-15 years). We administered the Paediatric Evaluation of Emotions, Relationships and Socialisation (PEERS) to children, and parents completed standardised questionnaires rating children's socio-emotional function. Standardised parent questionnaires revealed a global pattern of everyday socio-emotional impairment that was common to all clinical groups, while PEERS identified disorder-specific socio-cognitive profiles for children with ASD, ADHD and ANX. Compared to TDCs, children with ASD demonstrated global socio-cognitive impairment. Children with ADHD were impulsive, demonstrating difficulties managing speed accuracy trade-offs. Children with ANX exhibited slowed social decision-making, but otherwise intact skills. Standardized parent questionnaires of child socio-emotional function reveal differences between children with typical and atypical development, but do not yield disorder-specific, socio-emotional profiles. In contrast, findings from the PEERS objective assessment suggest that that ASD, ADHD and ANX are associated with distinct socio-cognitive phenotypes, to more accurately guide and target management and treatment of impaired social competence.
Journal Article
The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease
Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants. Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning. Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring. Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.
Journal Article
The effects of practice on the cognitive test performance of neurologically normal individuals assessed at brief test–retest intervals
Performance on many cognitive and neuropsychological tests may be improved by prior exposure to testing stimuli and procedures. These beneficial practice effects can have a significant impact on test performance when conventional neuropsychological tests are administered at test–retest intervals of weeks, months or years. Many recent investigations have sought to determine changes in cognitive function over periods of minutes or hours (e.g., before and after anesthesia) using computerized tests. However, the effects of practice at such brief test–retest intervals has not been reported. The current study sought to determine the magnitude of practice effects in a group of 113 individuals assessed with an automated cognitive test battery on 4 occasions in 1 day. Practice effects were evident both between and within assessments, and also within individual tests. However, these effects occurred mostly between the 1st and 2nd administration of the test battery, with smaller, nonsignificant improvements observed between the 2nd, 3rd, and 4th administrations. On the basis of these results, methodological and statistical strategies that may aid in the differentiation of practice effects from drug-induced cognitive changes are proposed. (JINS, 2003, 9, 419–428.)
Journal Article
3144 Consensus to clinic: enhancing diagnostics for posterior cortical atrophy
Background/ObjectivesNearly thirty thousand Australians under the age of 65 live with dementia. Posterior Cortical Atrophy (PCA) is one form of young onset atypical dementia, often caused by Alzheimer disease. Due to its rarity, atypical phenotype and young onset, the diagnosis is often missed for years. A consensus expert opinion diagnostic framework was created in 2017 to reduce delays to diagnosis. We aimed to test the validity of this framework in a real-world PCA population.MethodsWe completed a retrospective audit of Eastern Cognitive Disorders Clinic (ECDC) patients with a clinician-determined final diagnosis of PCA (N=32) 2008–2022: age at diagnosis, time to diagnosis and the clinical, cognitive, and neuro-imaging features. We compared our patients’ presentations with the core cognitive features included in the framework and their presence at first assessment.Results Thirty (93.8%) ECDC clinician diagnosed PCA patients fulfilled the criteria: cognitive features correlated well with the framework for the top four features (visuo-spatial and -perceptual deficits, simultanagnosia, constructional apraxia). 100% of patients had MRI brain, but only 38% were reported as PCA; 84% had FDG-PET brain with 59% reported as PCA. Most (28, 87.5%) presentations were in keeping with a PCA-pure syndrome. Three patients met criteria for PCA-plus-CBS and one for PCA-plus-DLB. Average delay to diagnosis was 4 years with mean symptom onset at age 59 years.ConclusionOur patients’ cognitive features closely aligned with the consensus framework, corroborating its real-world applicability. Neuroradiological reporting was identified as a key challenge. This represents new Australian data on PCA syndromic diagnosis.
Journal Article
Referral patterns and diagnostic outcomes in an outpatient Australian tertiary cognitive neurology service: 2009–2019
Introduction Young‐onset dementia (YOD) and atypical dementias often experience diagnostic delays, particularly in outpatient settings where timely referrals are crucial. Methods A 10‐year retrospective audit (2009–2019) of 626 patients at a specialist cognitive neurology clinic reviewed demographics, referral sources, and time to diagnosis. Data were compared between YOD and late‐onset dementia (LOD), and with and without dementia groups. Results Fifty‐three percent of patients were diagnosed with dementia (mean age: 65 ± 11.9 years). Non‐neurodegenerative conditions were more frequent in < 65 years (61%). Among YOD cases, Alzheimer's dementia (AD) and behavioral variant frontotemporal dementia accounted for 40% and 34% of diagnoses, respectively, while AD predominated in LOD (65%). Language‐variant dementias were similar between groups (14%). Diagnostic delays in YOD averaged 1 year longer than in LOD. Discussion Higher YOD and language‐variant dementia referrals to specialist services reveal diagnostic delays, underscoring the need for better referral and diagnostic pathways. Highlights Delayed diagnosis common in young‐onset dementia (YOD) and atypical dementia. Specialist clinics see more YOD and language‐variant dementia referrals. YOD has longer time from symptom onset to diagnosis compared to late‐onset cases. Behavioral variant frontotemporal dementia (bvFTD) a more common diagnosis in YOD patients.
Journal Article
3020 Frontal variant Alzheimer's dementia may not only be a syndrome of the under sixty-fives
Background/ObjectivesFrontal variant Alzheimer’s Disease (fvAD) is relatively recently characterised condition which has been traditionally regarded as a young onset dementia. Classically the diagnosis relied primarily on clinical criteria. However, with the advent of new biomarkers and imaging technology, we expect to see a better reflection of the true prevalence of this condition in the community.MethodsWe conducted a 10-year retrospective audit of all patients presenting to an outpatient specialist cognitive neurology clinic from 2009 to 2019.Results626 patients were seen over this period with 334 receiving a diagnosis of dementia. In the 65 and over age group, Alzheimer’s Dementia (AD) was the predominant diagnosis accounting for 59% of all dementia. Under 65 years, AD and behavioural variant Frontotemporal Dementia (bvFTD) patients represented 40% and 34% of the diagnoses, respectively. A total of ten patients were diagnosed with fvAD, seven of whom were aged over 65 years.ConclusionFrontal variant AD was an uncommon diagnosis in our study making up 3% of the total dementia diagnosis over 10 years. The majority of those were in the late onset dementia group, meaning that dysexecutive profiles in older people with dementia are still most likely due to AD pathology. We note that the use of imaging techniques including FDG-PET, and new plasma biomarkers, may have assisted in better identifying a relatively recently characterised condition. Our findings would suggest that fvAD is less common in those under 65, with most patients in that group being diagnosed with bvFTD.
Journal Article