What is the best noninvasive diagnostic test for women with suspected CAD?

Multidetector computed tomography (MDCT) may be the most sensitive and specific noninvasive diagnostic test for women with suspected coronary artery disease (CAD) (strength of recommendation [SOR]: A, multiple prospective cohort studies). However, stress echocardiography and nuclear medicine perfusion testing are still the best well-tested and readily available alternatives in light of the newness of MDCT and concerns regarding its use (SOR: A, meta-analysis and cohort studies). Standard exercise treadmill testing (ETT) doesn't adequately exclude or confirm CAD in women (SOR: A, multiple prospective cohort studies)

History of Belfield

https://digitalcommons.lasalle.edu/belfield_books/1002/thumbnail.jp

What are ventilation defects in asthma?

BACKGROUND: Hyperpolarised (3)He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood. OBJECTIVE: To better understand the determinants of ventilation defects in asthma, we evaluated well-established clinical as well as (3)He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma. METHODS: Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3(rd) to 5th generation airway wall area and wall thickness per cent and lumen area. RESULTS: Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of (3)He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV1)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV1 by 20% (p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04). CONCLUSIONS: Subjects with asthma with (3)He ventilation defects were older with significantly worse airway hyper-responsiveness, inflammation and airway remodelling but similar FEV1 as subjects with asthma without defects; hyperpolarised (3)He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways

A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition

<p>Abstract</p> <p>Background</p> <p>Non-pathological cognitive ageing is a distressing condition affecting an increasing number of people in our 'ageing society'. Oxidative stress is hypothesised to have a major role in cellular ageing, including brain ageing.</p> <p>Results</p> <p>Associations between cognitive ageing and 325 single nucleotide polymorphisms (SNPs), located in 109 genes implicated in oxidative stress and/or cognition, were examined in a unique cohort of relatively healthy older people, on whom we have cognitive ability scores at ages 11 and 79 years (LBC1921). SNPs showing a significant positive association were then genotyped in a second cohort for whom we have cognitive ability scores at the ages of 11 and 64 years (ABC1936). An intronic SNP in the <it>APP </it>gene (rs2830102) was significantly associated with cognitive ageing in both LBC1921 and a combined LBC1921/ABC1936 analysis (<it>p </it>< 0.01), but not in ABC1936 alone.</p> <p>Conclusion</p> <p>This study suggests a possible role for APP in normal cognitive ageing, in addition to its role in Alzheimer's disease.</p

From 'aisle' to 'labile': a hierarchical NART scale revealed by Mokken scaling

Decline in cognitive ability is a core diagnostic criterion for dementia. Knowing the extent of decline requires a baseline score from which change can be reckoned. In the absence of prior cognitive ability scores, vocabulary-based cognitive tests are used to estimate premorbid cognitive ability. It is important that such tests are short yet informative, to maximize information and practicability. The National Adult Reading Test (NART) is commonly used to estimate premorbid intelligence. People are asked to pronounce 50 words ranging from easy to difficult but whether its words conform to a hierarchy is unknown. Five hundred eighty-seven healthy community-dwelling older people with known age 11 IQ scores completed the NART as part of the Lothian Birth Cohort 1936 study. Mokken analysis was used to explore item responses for unidimensional, ordinal, and hierarchical scales. A strong hierarchical scale (“mini-NART”) of 23 of the 50 items was identified. These items are invariantly ordered across all ability levels. The validity of the interpretation of this briefer scale’s score as an estimate of premorbid ability was examined using the actual age 11 IQ score. The mini-NART accounted for a similar amount of the variance in age 11 IQ as the full NART (NART = 46.5%, mini-NART = 44.8%). The mini-NART is proposed as a useful short clinical tool to estimate prior cognitive ability. The mini-NART has clinical relevance, comprising highly discriminatory, invariantly ordered items allowing for sensitive measurement, and adaptive testing, reducing test administration time, and patient stress

Alzheimer's Disease Genes Are Associated with Measures of Cognitive Ageing in the Lothian Birth Cohorts of 1921 and 1936

Alzheimer's disease patients have deficits in specific cognitive domains, and susceptibility genes for this disease may influence human cognition in nondemented individuals. To evaluate the role of Alzheimer's disease-linked genetic variation on cognition and normal cognitive ageing, we investigated two Scottish cohorts for which assessments in major cognitive domains are available: the Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936, consisting of 505 and 998 individuals, respectively. 158 SNPs from eleven genes were evaluated. Single SNP analyses did not reveal any statistical association after correction for multiple testing. One haplotype from TRAPPC6A was associated with nonverbal reasoning in both cohorts and combined data sets. This haplotype explains a small proportion of the phenotypic variability (1.8%). These findings warrant further investigation as biological modifiers of cognitive ageing

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

Non-parametric item response theory applications in the assessment of dementia

This thesis sought to address the application of non-parametric item response theory (NIRT) to cognitive and functional assessment in dementia. Performance on psychometric tests is key to diagnosis and monitoring of dementia. NIRT can be used to improve the psychometric properties of tests used in dementia assessment in multiple ways: confirming an underlying unidimensional structure, establishing formal item hierarchical patterns of decline, increasing insight by examining item parameters such as difficulty and discrimination, and creating shorter tests. From a NIRT approach item difficulty refers to the ease with which an item is endorsed. Discrimination is an index of how well an item can differentiate between patients of varying levels of severity. Firstly I carried out a systematic review to identify applications of both parametric and non-parametric IRT to measures assessing global cognitive functioning in people with dementia. This review demonstrated that IRT can increase the interpretive power of cognitive assessment scales and confirmed the limited number of IRT analyses of cognitive scales in dementia populations. This thesis extended this approach by applying Mokken scaling analysis to commonly used measures of current cognitive ability (Addenbrooke’s Cognitive Examination-Revised (ACE-R)) and of premorbid cognitive ability (National Adult Reading Test (NART)). Differential item functioning (DIF) by diagnosis identified slight variations in the patterns of hierarchical decline in the ACE-R. These disease-specific sequences of decline could serve as an adjunct to diagnosis, for example where learning a name and address is a more difficult task than being orientated in time, late onset Alzheimer’s disease is a more probable diagnosis than mixed Alzheimer’s and vascular dementia. These analyses also allowed key items to be identified which can be used to create briefer scales (mini-ACE and Mini-NART) which have good psychometric properties. These scales are clinically relevant, comprising highly discriminatory, invariantly ordered items. They also allow sensitive measurement and adaptive testing and can reduce test administration time and patient stress. Impairment of functional abilities represents a crucial component of dementia diagnosis with performance on these functional tasks predictive of overall disease. A second aspect of this thesis, therefore, was the application of Mokken scaling analyses to measures of functional decline in dementia, specifically the Lawton Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS). While gender DIF was observed for several items, implying the likelihood of equal responses from men and women is not equal a generally consistent pattern of impairment in functional ability was observed across different types of dementia