Tara Coughlan

Multiple Indices of Diffusion Identifies White Matter Damage in Mild Cognitive Impairment and Alzheimer’s Disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimers disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa.

Using support vector machines with multiple indices of diffusion for automated classification of mild cognitive impairment.

Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimers disease where the early identification of subjects with MCI is critical.

Knowledge, skills and attitudes of doctors towards assessing cognition in older patients in the emergency department.

Purpose of the study Although cognitive impairment and delirium are highly prevalent in older patients who present to the emergency department, multiple studies have highlighted inadequate detection by doctors. This study investigated potential reasons underlying this. Study Design A 14-item self-administered questionnaire was distributed to all medical, surgical and emergency department physicians involved in the care of older patients in the emergency department of an urban university teaching hospital between January and March 2012. Results The questionnaire was completed by 76/97 (78%) of eligible respondents. Respondents reported screening an average of one in four older patients that they reviewed. Almost one-third (22/76, 29%) felt they lacked the relevant expertise to perform cognitive screening: those with training in geriatrics were less likely to cite lack of expertise as a factor. While the majority felt screening for cognition in the emergency department-setting was important (59/76, 78%), several limiting factors were identified: lack of a screening tool; lack of privacy; too much noise; and time constraints. There was no consensus on who should perform screening. Conclusions Doctors reviewing patients in the emergency department-setting reported several important factors limiting their ability to screen older patients for cognitive impairment. Respondents to this questionnaire did not feel the emergency department environment was conducive towards the assessment of cognition in older patients. Clarification of each disciplines responsibility in the detection, assessment and management of delirium and/or dementia, and the implementation of emergency department cognitive screening instruments more suited to this setting would likely improve detection and management.

Using Diffusion Tensor Imaging and Mixed-Effects Models to Investigate Primary and Secondary White Matter Degeneration in Alzheimer's Disease and Mild Cognitive Impairment

White matter (WM) degeneration in Alzheimers disease (AD) and mild cognitive impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with mixed-effects models. Four indices of diffusion were assessed in 61 healthy control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of the study was to use advanced mixed-effects models to investigate the retrogenesis hypothesis of AD, which suggests that tracts that are late to myelinate in ontogenetic development are the earliest to be affected in AD. Our results show that a number of late-myelinating pathways, including the parahippocampal region and the inferior longitudinal fasciculus, were predominantly affected by changes in WM volume. Conversely, early-myelinating pathways were found to be affected by a combination of both WM and gray matter (GM) atrophy. A model of the entire WM structure of the brain returned GM models for two indices of diffusion, suggesting that more complex regional landscapes of diffusion lie hidden beneath a global analysis of the entire brain. Our results warn against an explanation of white matter damage that points simply to one of two mechanisms: secondary degeneration or direct damage of myelin. We suggest that tracts may be affected by both mechanisms, with the balance depending on whether tracts are early or late-myelinating. A greater understanding of the pattern of WM changes in AD may prove useful for the early detection of AD.

Subjective memory complaints in community dwelling healthy older people: the influence of brain and psychopathology†

Subjective memory complaints (SMC) are common. We aimed to characterize the relationship between psychiatric illness and white matter disease to SMC in a sample of healthy older people.

Prevalence of Ex Vivo High On-treatment Platelet Reactivity on Antiplatelet Therapy after Transient Ischemic Attack or Ischemic Stroke on the PFA-100® and VerifyNow®

BACKGROUND The prevalence of ex vivo high on-treatment platelet reactivity (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic attack (TIA) or ischemic stroke is uncertain. METHODS Platelet function inhibition was simultaneously assessed with modified light transmission aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic stroke patients. Patients were assessed on aspirin-dipyridamole combination therapy (n = 51) or clopidogrel monotherapy (n = 25). RESULTS On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥ 550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥ 194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001). CONCLUSIONS The prevalence of ex vivo antiplatelet HTPR after TIA or ischemic stroke is markedly influenced by the method used to assess platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of platelet function are warranted to assess whether platelet function monitoring predicts clinical outcome in ischemic cerebrovascular disease.

Characteristics and outcomes of older persons attending the emergency department: a retrospective cohort study

BACKGROUND The analysis of routinely collected hospital data informs the design of specialist services for at-risk older people. AIM Describe the outcomes of a cohort of older emergency department (ED) attendees and identify predictors of these outcomes. DESIGN retrospective cohort study. METHODS All patients aged 65 years or older attending an urban university hospital ED in January 2012 were included (N = 550). Outcomes were retrospectively followed for 12 months. Statistical analyses were based on multivariate binary logistic regression models and classification trees. RESULTS Of N = 550, 40.5% spent ≤6 h in the ED, but the proportion was 22.4% among those older than 81 years and not presenting with musculoskeletal problems/fractures. N = 349 (63.5%) were admitted from the ED. A significant multivariate predictor of in-hospital mortality was Charlson comorbidity index [CCI; odds ratio = 1.19, 95% confidence interval: 1.07, 1.34, P = 0.002]. Among patients who were discharged from ED without admission or after their first in-patient admission (N = 499), 232 (46.5%) re-attended ED within 1 year, with CCI being the best predictor of re-attendance (CCI ≤ 4: 25.8%, CCI > 5: 60.4%). Among N = 499, 34 (6.8%) had died after 1 year of initial ED presentation. The subgroup (N = 114) with the highest mortality (17.5%) was composed by those aged >77 years and brought in by ambulance on initial presentation. CONCLUSIONS Advanced age and comorbidity are important drivers of outcomes among older ED attendees. There is a need to embed specialist geriatric services within frontline services to make them more gerontologically attuned. Our results predate the opening of an acute medical unit with specialist geriatric input.

Mapping patients’ experiences after stroke onto a patient-focused intervention framework

Background: Stroke patients’ involvement in the rehabilitation process including decision making has made significant advances clinically over the past two decades. However, development of patient-focused interventions in stroke rehabilitation is a relatively under developed area of research. The aim of this study was to interpret the explanations that patients gave of their experience after stroke and how these may validate an already established patient-focused intervention framework – the Quest for quality and improved performance (QQUIP) (2006) that includes seven quality improvement goals. Methods: A random purposive sample of eight stroke patients was interviewed between 3 and 6 months following discharge. Patients’ reports of their experience after stroke were obtained using in-dept semi-structured interviews and analysed using Qualitative Content Analysis. Results: Explanations given by patients included both positive and negative reports of the stroke experience. Regardless of consequences as a result of physical, psychological and social impairments, there were other life style disruptions that were reported by all patients such as taking new medication and adverse effects of these, experiencing increasing fatigue, difficulties with social activities and situations and having to make changes in health behaviours and lifestyle. Some of the core themes that emerged reflected the aims of QQUIP improvement goals that include improving health literacy, clinical decision-making, self-care, patient safety, access to health advice, care experience and service development. Discussion: Further recommendations based on the findings from this study would be to consider using the QQUIP framework for developing intervention studies in stroke rehabilitation care that are person-centred. This framework provides a template that is equipped to address some of the main concerns that people have following the experience of stroke and also focuses on improving quality of care. Implications for Rehabilitation Consideration for the use of established patient focused frameworks for improving the design and development of rehabilitation stroke interventions. Identify patients’ main concerns following the experience of stroke and its resulting consequences in developing stroke rehabilitation interventions Greater need to move from a provider-led model of care towards a more favourably balanced view that includes patient participation and involvement in their self management of the rehabilitation programme required

High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke: results from the Trinity Antiplatelet Responsiveness (TRAP) study

The prevalence of ex vivo ‘high on‐treatment platelet reactivity’ (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain.

Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study.

Ex vivo dipyridamole ‘non‐responsiveness’ has not been extensively studied in ischaemic cerebrovascular disease. Platelet surface marker expression, leucocyte‐platelet complex formation and inhibition of platelet function at high shear stress as detected by the PFA‐100® Collagen‐Adenosine‐diphosphate (C‐ADP) and Collagen‐Epinephrine cartridges was assessed in 52 patients within 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14 d (14 d) and >90 d (90 d) after adding dipyridamole. A novel definition of ‘Dipyridamole non‐responsiveness’ was used. The median C‐ADP closure time increased following addition of dipyridamole, remained elevated at 90 d (P ≤ 0·03), and was unaffected by aspirin dose. 59% at 14 d and 56% at 90 d were ‘dipyridamole non‐responders’ on the PFA‐100. The proportion of non‐responders at 14 and 90 d was similar (P = 0·9). Compared with baseline (4·6%), median monocyte‐platelet complexes increased at 14 d (5·0%, P = 0·03) and 90 d (4·9%, P = 0·04). Low C‐ADP closure times were associated with increased monocyte‐platelet complexes at 14 d (r = −0·32, P = 0·02) and 90 d (r = −0·33, P = 0·02). Monocyte‐platelet complexes increased in the subgroup of dipyridamole non‐responders on the PFA‐100 (P ≤ 0·045), but not in responders (P ≥ 0·5), at 14 and 90 d versus baseline. Additional inhibition of platelet function has been detected with the PFA‐100 when dipyridamole is added to aspirin. Elevated monocyte‐platelet complexes may contribute to ex vivo dipyridamole non‐responsiveness.