James FM F Meaney - Academia.edu (original) (raw)

Papers by James FM F Meaney

The New England Journal of Medicine, May 15, 1997

Neuropsychopharmacology, Aug 22, 2012

Genes and early-life adversity (ELA) interactively increase the risk of developing major depressi... more Genes and early-life adversity (ELA) interactively increase the risk of developing major depressive disorder (MDD). A recent genomewide association study suggests that the minor T-allele of single-nucleotide polymorphisms in the bicaudal C homolog 1 gene (BICC1) has a protective role against MDD. The aims of the study were to investigate whether the minor T-allele of BICC1 is protective against hippocampal structural brain changes, whether it is associated with increased functional brain activity in the emotion regulation system, and how ELA would modify this association. Forty-four patients with MDD and 44 healthy controls were investigated using structural magnetic resonance imaging (MRI) and functional MRI with an emotion inhibition task. Analysis of a single-nucleotide polymorphism in the BICC1-1 (rs999845) gene was performed. Right hippocampal bodies of patients and controls without a history of ELA and who carry the protective T-allele of BICC1 were significantly larger compared with those participants homozygous for the major C-allele of BICC1. However, MDD patients with ELA, who carry the T-allele, had smaller hippocampal head volumes compared with MDD patients without ELA. FMRI showed that patients and controls carrying the protective T-allele of BICC1 activate the emotion regulation system significantly more compared with those participants homozygous for the major C-allele (po0.05, family wise error corrected). These results are suggestive that the minor T-allele of BICC1 has a protective role against MDD and its known structural and functional brain changes. However, this protective effect seems to be lost in the case of co-occurrence of ELA.

Medical Sciences, May 22, 2019

Introduction: diaphragmatic dysfunction is a common cause of slow weaning in mechanically ventila... more Introduction: diaphragmatic dysfunction is a common cause of slow weaning in mechanically ventilated patients. Diaphragmatic dysfunction in ventilated patients can be global or regional. The aim of our study was to evaluate the motion of the entire diaphragm in patients who were ventilated for a protracted period in comparison with healthy controls by using Magnetic Resonance Imaging (MRI). Methods: Intensive care patients who had a prolonged ventilator wean and required tracheostomies were enrolled based on extensive exclusion criteria. MRI dynamic sequence and subtraction images were used to measure vertical displacement at five different points on each hemi-diaphragm during normal tidal breathing. Tidal displacement of each point on the right and left hemi-diaphragms of the patients were compared to the precise respective points on the right and left hemi-diaphragms of enrolled controls. Results: Eight intensive care patients and eight controls were enrolled. There were observed significant differences in the displacements of the left hemi-diaphragm between the two groups (median 6.4 mm [Interquartile range (IQR), 4.6-12.5]) vs. 11.6 mm [IQR, 9.5-14.5], p = 0.02). There were also observed significant differences in the displacements at five evaluated study points on the left hemi-diaphragms of the patients when compared to the precise respective points in controls, especially at the dome (median 6.7 mm [IQR, 5.0-11.4] vs. 13.5 mm [IQR 11.5-18], p value = 0.005) and the anterior zone of apposition (median 5.0 mm [IQR, 3.3-7.1] vs. 7.8mm [IQR, 7.1-10.5], p value = 0.01). The intensive care patients showed lower minimal and maximal values of displacement of right hemi-diaphragms compared to the controls, suggesting that the differences in the displacement of right hemi-diaphragm are possible; however, the differences in the mean values of displacement of right hemi-diaphragm between the intensive care patient group and the control group (median 9.8 mm [IQR (Interquartile range), 5.0-12.3] vs. 10.1 mm [IQR 8.3-18.5], p = 0.12) did not reach the level of significance. Conclusion: Although frequently global, diaphragm dysfunction in ventilated patients after prolonged ventilation can also be regional or focal when assessed by MRI dynamic sequence. The vertical displacement of both right and left hemi-diaphragms at various anatomical locations had different values in both controls, and patients. There were significant focal variations in the movement of diaphragm in patients with ventilator-induced diaphragmatic dysfunction.

Journal of Maternal-fetal & Neonatal Medicine, Dec 6, 2011

Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with sys... more Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with systemic infectious symptoms. In the literature it rarely occurs postpartum. We report a case of piriformis pyomyositis involving a parturient and review the published cases available in the literature.

Scientific Reports, Jul 29, 2019

The heterogeneous specialisation of hippocampal subfields across memory functions has been widely... more The heterogeneous specialisation of hippocampal subfields across memory functions has been widely shown in animal models. Yet, few in vivo studies in humans have explored correspondence between hippocampal subfield anatomy and memory performance in ageing. Here, we used a well-validated automated MR segmentation protocol to measure hippocampal subfield volumes in 436 non-demented adults aged 50+. We explored relationships between hippocampal subfield volume and verbal episodic memory, as indexed by word list recall at immediate presentation and following delay. In separate multilevel models for each task, we tested linearity and non-linearity of associations between recall performance and subfield volume. Fully-adjusted models revealed that immediate and delayed recall were both associated with cubic fits with respect to volume of subfields CA1, CA2/3, CA4, molecular layer, and granule cell layer of dentate gyrus; moreover, these effects were partly dissociable from quadratic age trends, observed for subiculum, molecular layer, hippocampal tail, and CA1. Furthermore, analyses of semantic fluency data revealed little evidence of robust associations with hippocampal subfield volumes. Our results show that specific hippocampal subfields manifest associations with memory encoding and retrieval performance in non-demented older adults; these effects are partly dissociable from age-related atrophy, and from retrieval of well-consolidated semantic categories. Hippocampus is among the most important brain structures involved in memory 1-3 , and is a critical site of pathogenesis in dementing illnesses such as Alzheimer's Disease 4-7. Decades of ex vivo human studies and in vivo animal studies have revealed anatomical and functional heterogeneity of the hippocampal subfields 8-12. Yet, until recently, very few in vivo studies in humans had shown dissociable relationships between performance in different memory domains and hippocampal subfield anatomy or function 13-15. The role of the hippocampal subfields with respect to select domains of memory thus remains under explored. Recent work has shown that errors during real-world spatial navigation are negatively associated with hippocampal tail volume in mild cognitive impairment (MCI), but with Cornu Ammonis (CA) 3 volume in healthy controls 16. Yet, despite this, there remains a limited understanding of the role of hippocampal subfields in other memory domains relied on in daily life, such as verbal episodic memory (e.g., recalling a grocery list) or semantic memory (e.g., retrieving familiar nouns) [but see 17 ]. Verbal episodic and semantic memory have been shown to dissociate to hippocampal versus anterior temporal regions respectively 18-22. However, much of our understanding of these dissociations is based on small and heterogeneous patient cohorts 19-21. Little is known about these relationships in the context of healthy ageing; less still is known about the effects of age with respect to relationships between hippocampal subfields and specific memory domains, despite evidence of age-related variation in subfield anatomy 23-25 .

European Radiology, Mar 25, 2003

The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magneti... more The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magnetic resonance angiography (CE MRA), using 1.0-mol gadobutrol, with intra-arterial digital subtraction angiography (i.a. DSA) for evaluation of pelvic and peripheral arteries in patients with peripheral arterial occlusive disease. A total of 203 patients were examined in a prospective, multi-centre study at 1.0/1.5 T. Ten vessel segments of one leg were evaluated on-site and by three independent blinded reviewers off-site. One hundred eighty-two patients were evaluable in blinded reading. For pelvis and thigh, there was statistically significant diagnostic agreement between CE MRA and i.a. DSA on-site (94%) and off-site (86-88%). Overall, for detection of clinically significant stenoses, 93% sensitivity and 90% specificity were achieved in on-site evaluation, with 71-76 and 87-93% off-site; for detection of occlusion, sensitivity and specificity on-site were 91 and 97%, with 75-82 and 94-98% off-site. Evaluation was more sensitive on-site than off-site for detection of stenoses and occlusion, whereas specificity was similar. The CE MRA with 1.0-mol gadobutrol gave results comparable to those of i.a. DSA for the larger arteries of pelvis and thigh. Results for calf arteries were compromised by spatial resolution and technical limitations.

Frontiers in Aging Neuroscience

BackgroundFrailty in older adults has been associated with reduced brain health. However, structu... more BackgroundFrailty in older adults has been associated with reduced brain health. However, structural brain signatures of frailty remain understudied. Our aims were: (1) Explore associations between a frailty index (FI) and brain structure on magnetic resonance imaging (MRI). (2) Identify the most important FI features driving the associations.MethodsWe designed a cross-sectional observational study from a population-based study (The Irish Longitudinal Study on Aging: TILDA). Participants aged ≥50 years who underwent the wave 3 MRI sub-study were included. We measured cortex, basal ganglia, and each of the Desikan-Killiany regional volumes. Age-and sex-adjusted correlations were performed with a 32-item self-reported FI that included conditions commonly tested for frailty in research and clinical settings. A graph theory analysis of the network composed by each FI item and cortex volume was performed. White matter fiber integrity was quantified using diffusion tensor imaging (DTI).Re...

Neurobiology of Aging, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

American Journal of Case Reports, 2020

Patient: Male, 32-year-old Final Diagnosis: Granulomatous amebic encephalitis Symptoms: — Medicat... more Patient: Male, 32-year-old Final Diagnosis: Granulomatous amebic encephalitis Symptoms: — Medication:— Clinical Procedure: — Specialty: — Objective: Challenging differential diagnosis Background: Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. Case Report: We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. Conclusions: We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Neurobiology of Aging, 2021

This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist ci... more This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and physical activity (PA) with gray matter cerebral blood flow (CBF GM) in older adults. Cross-sectional data was used from the Irish Longitudinal Study on Ageing (n = 495, age 69.0 ±7.4 years, 52.1% female). Whole-brain CBF GM was quantified using arterial spin labeling MRI. Results from multivariable regression analysis revealed that an increase in BMI of 0.43 kg/m 2 , WHR of 0.01, or WC of 1.3 cm were associated with the same reduction in CBF GM as 1 year of advancing age. Participants overweight by BMI or with high WHR/WC reporting low/moderate PA had up to 3 ml/100g/min lower CBF GM (p ≤ .011); there was no significant reduction for those reporting high PA. Since PA could potentially moderate obesity/CBF associations, this may be a cost-effective and relatively easy way to help mitigate the negative impact of obesity in an older population, such as cerebral hypoperfusion, which is an early mechanism in vascular dementia and Alzheimer's disease.

NeuroImage, 2021

Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF... more Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF GM) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older. Background: Quantitative assessment of CBF GM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBF GM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion. Methods: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBF GM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations. Results: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBF GM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBF GM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = − 0.3, − 0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001). Conclusions: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBF GM measured at 3T using pCASL-MRI. Significant age-and sex-related differences exist in CBF GM .

JRSM Cardiovascular Disease, 2020

Introduction Orthostatic Hypotension (OH) is an abnormal drop in blood pressure (BP) that occurs ... more Introduction Orthostatic Hypotension (OH) is an abnormal drop in blood pressure (BP) that occurs following orthostatic challenge. OH is associated with increased risk of falls, cognitive impairment and death. White Matter Hyperintensities (WMH) on MR Brain are associated with vascular risk factors such as hypertension, diabetes and age. We examined whether extent White matter intensities were associated with presence of OH detected in a community dwelling population of older people. Methods Individuals from the MR sub-study of the Irish Longitudinal Study of Ageing underwent a 3 Tesla MR Brain scan to assess WMH severity (Schelten’s Score). The scans were performed during the Wave 3 TILDA health assessment phase when the subjects also underwent assessment for OH with an active stand protocol. Data was analysed for association between WMH and vascular risks and orthostatic change in BP 10 second intervals during the OH evaluation. Results 440 subjects were investigated; median age 72...

Irish Journal of Medical Science (1971 -), 2020

Background and aims A significant proportion of patients presenting to the Emergency Department w... more Background and aims A significant proportion of patients presenting to the Emergency Department with gastrointestinal symptoms that result in cross-sectional imaging receive a radiological diagnosis of colitis. We aimed to review the characteristics, outcomes, and final diagnoses of new emergency department presentations with colitis diagnosed on cross-sectional imaging. Methods A radiology database was interrogated to identify patients admitted from the Emergency Department of St James's Hospital whose cross-sectional imaging demonstrated colitis. Baseline demographic data, information on inpatient investigations, final diagnoses, and outcomes were recorded. Adverse outcomes were defined as a requirement for surgery, intensive care unit (ICU) stay, or mortality Results A total of 118 patients, 67% female, were identified with a median age of 64 years (range 16.9-101.2). Median (range) admission duration was 10 days (1-241). Final colitis diagnoses were infectious (28%), undefined (27%), reactive (18%), inflammatory bowel disease (11%), ischaemic (9%), chemotherapy-associated (3%), diverticular (3%), and medication-associated (1%). Colonic perforation, colectomy, and mortality occurred in 1%, 5%, and 13% of the cohort respectively. On univariate analysis, low haemoglobin, low albumin, high lactate, and male gender were associated with adverse outcomes with the following odds ratios (OR) and 95% confidence intervals (95%CI) were low haemoglobin 1.

Journal of Cerebral Blood Flow & Metabolism, 2019

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet bio... more The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation. We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray–Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as ‘MES+ve’ or ‘MES-ve’. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets. Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (...

International Journal of Epidemiology, 2018

Irish Journal of Medical Science (1971 -), 2015

Background Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainste... more Background Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio. Objective We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI. Methods Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography. Results Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006). Conclusion In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS.

Physics in medicine and biology, Oct 3, 2016

A novel anthropomorphic flow phantom device has been developed, which can be used for quantitativ... more A novel anthropomorphic flow phantom device has been developed, which can be used for quantitatively assessing the ability of magnetic resonance imaging (MRI) scanners to accurately measure signal/concentration time-intensity curves (CTCs) associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex pharmacokinetics of contrast agents as they perfuse through the tumour capillary network has shown great promise for cancer diagnosis and therapy monitoring. However, clinical adoption has been hindered by methodological problems, resulting in a lack of consensus regarding the most appropriate acquisition and modelling methodology to use and a consequent wide discrepancy in published data. A heretofore overlooked source of such discrepancy may arise from measurement errors of tumour CTCs deriving from the imaging pulse sequence itself, while the effects on the fidelity of CTC measurement of using rapidly-accelerated sequences such as parallel imaging and compressed sensi...

The New England Journal of Medicine, May 15, 1997

Neuropsychopharmacology, Aug 22, 2012

Genes and early-life adversity (ELA) interactively increase the risk of developing major depressi... more Genes and early-life adversity (ELA) interactively increase the risk of developing major depressive disorder (MDD). A recent genomewide association study suggests that the minor T-allele of single-nucleotide polymorphisms in the bicaudal C homolog 1 gene (BICC1) has a protective role against MDD. The aims of the study were to investigate whether the minor T-allele of BICC1 is protective against hippocampal structural brain changes, whether it is associated with increased functional brain activity in the emotion regulation system, and how ELA would modify this association. Forty-four patients with MDD and 44 healthy controls were investigated using structural magnetic resonance imaging (MRI) and functional MRI with an emotion inhibition task. Analysis of a single-nucleotide polymorphism in the BICC1-1 (rs999845) gene was performed. Right hippocampal bodies of patients and controls without a history of ELA and who carry the protective T-allele of BICC1 were significantly larger compared with those participants homozygous for the major C-allele of BICC1. However, MDD patients with ELA, who carry the T-allele, had smaller hippocampal head volumes compared with MDD patients without ELA. FMRI showed that patients and controls carrying the protective T-allele of BICC1 activate the emotion regulation system significantly more compared with those participants homozygous for the major C-allele (po0.05, family wise error corrected). These results are suggestive that the minor T-allele of BICC1 has a protective role against MDD and its known structural and functional brain changes. However, this protective effect seems to be lost in the case of co-occurrence of ELA.

Medical Sciences, May 22, 2019

Introduction: diaphragmatic dysfunction is a common cause of slow weaning in mechanically ventila... more Introduction: diaphragmatic dysfunction is a common cause of slow weaning in mechanically ventilated patients. Diaphragmatic dysfunction in ventilated patients can be global or regional. The aim of our study was to evaluate the motion of the entire diaphragm in patients who were ventilated for a protracted period in comparison with healthy controls by using Magnetic Resonance Imaging (MRI). Methods: Intensive care patients who had a prolonged ventilator wean and required tracheostomies were enrolled based on extensive exclusion criteria. MRI dynamic sequence and subtraction images were used to measure vertical displacement at five different points on each hemi-diaphragm during normal tidal breathing. Tidal displacement of each point on the right and left hemi-diaphragms of the patients were compared to the precise respective points on the right and left hemi-diaphragms of enrolled controls. Results: Eight intensive care patients and eight controls were enrolled. There were observed significant differences in the displacements of the left hemi-diaphragm between the two groups (median 6.4 mm [Interquartile range (IQR), 4.6-12.5]) vs. 11.6 mm [IQR, 9.5-14.5], p = 0.02). There were also observed significant differences in the displacements at five evaluated study points on the left hemi-diaphragms of the patients when compared to the precise respective points in controls, especially at the dome (median 6.7 mm [IQR, 5.0-11.4] vs. 13.5 mm [IQR 11.5-18], p value = 0.005) and the anterior zone of apposition (median 5.0 mm [IQR, 3.3-7.1] vs. 7.8mm [IQR, 7.1-10.5], p value = 0.01). The intensive care patients showed lower minimal and maximal values of displacement of right hemi-diaphragms compared to the controls, suggesting that the differences in the displacement of right hemi-diaphragm are possible; however, the differences in the mean values of displacement of right hemi-diaphragm between the intensive care patient group and the control group (median 9.8 mm [IQR (Interquartile range), 5.0-12.3] vs. 10.1 mm [IQR 8.3-18.5], p = 0.12) did not reach the level of significance. Conclusion: Although frequently global, diaphragm dysfunction in ventilated patients after prolonged ventilation can also be regional or focal when assessed by MRI dynamic sequence. The vertical displacement of both right and left hemi-diaphragms at various anatomical locations had different values in both controls, and patients. There were significant focal variations in the movement of diaphragm in patients with ventilator-induced diaphragmatic dysfunction.

Journal of Maternal-fetal & Neonatal Medicine, Dec 6, 2011

Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with sys... more Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with systemic infectious symptoms. In the literature it rarely occurs postpartum. We report a case of piriformis pyomyositis involving a parturient and review the published cases available in the literature.

Scientific Reports, Jul 29, 2019

The heterogeneous specialisation of hippocampal subfields across memory functions has been widely... more The heterogeneous specialisation of hippocampal subfields across memory functions has been widely shown in animal models. Yet, few in vivo studies in humans have explored correspondence between hippocampal subfield anatomy and memory performance in ageing. Here, we used a well-validated automated MR segmentation protocol to measure hippocampal subfield volumes in 436 non-demented adults aged 50+. We explored relationships between hippocampal subfield volume and verbal episodic memory, as indexed by word list recall at immediate presentation and following delay. In separate multilevel models for each task, we tested linearity and non-linearity of associations between recall performance and subfield volume. Fully-adjusted models revealed that immediate and delayed recall were both associated with cubic fits with respect to volume of subfields CA1, CA2/3, CA4, molecular layer, and granule cell layer of dentate gyrus; moreover, these effects were partly dissociable from quadratic age trends, observed for subiculum, molecular layer, hippocampal tail, and CA1. Furthermore, analyses of semantic fluency data revealed little evidence of robust associations with hippocampal subfield volumes. Our results show that specific hippocampal subfields manifest associations with memory encoding and retrieval performance in non-demented older adults; these effects are partly dissociable from age-related atrophy, and from retrieval of well-consolidated semantic categories. Hippocampus is among the most important brain structures involved in memory 1-3 , and is a critical site of pathogenesis in dementing illnesses such as Alzheimer's Disease 4-7. Decades of ex vivo human studies and in vivo animal studies have revealed anatomical and functional heterogeneity of the hippocampal subfields 8-12. Yet, until recently, very few in vivo studies in humans had shown dissociable relationships between performance in different memory domains and hippocampal subfield anatomy or function 13-15. The role of the hippocampal subfields with respect to select domains of memory thus remains under explored. Recent work has shown that errors during real-world spatial navigation are negatively associated with hippocampal tail volume in mild cognitive impairment (MCI), but with Cornu Ammonis (CA) 3 volume in healthy controls 16. Yet, despite this, there remains a limited understanding of the role of hippocampal subfields in other memory domains relied on in daily life, such as verbal episodic memory (e.g., recalling a grocery list) or semantic memory (e.g., retrieving familiar nouns) [but see 17 ]. Verbal episodic and semantic memory have been shown to dissociate to hippocampal versus anterior temporal regions respectively 18-22. However, much of our understanding of these dissociations is based on small and heterogeneous patient cohorts 19-21. Little is known about these relationships in the context of healthy ageing; less still is known about the effects of age with respect to relationships between hippocampal subfields and specific memory domains, despite evidence of age-related variation in subfield anatomy 23-25 .

European Radiology, Mar 25, 2003

The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magneti... more The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magnetic resonance angiography (CE MRA), using 1.0-mol gadobutrol, with intra-arterial digital subtraction angiography (i.a. DSA) for evaluation of pelvic and peripheral arteries in patients with peripheral arterial occlusive disease. A total of 203 patients were examined in a prospective, multi-centre study at 1.0/1.5 T. Ten vessel segments of one leg were evaluated on-site and by three independent blinded reviewers off-site. One hundred eighty-two patients were evaluable in blinded reading. For pelvis and thigh, there was statistically significant diagnostic agreement between CE MRA and i.a. DSA on-site (94%) and off-site (86-88%). Overall, for detection of clinically significant stenoses, 93% sensitivity and 90% specificity were achieved in on-site evaluation, with 71-76 and 87-93% off-site; for detection of occlusion, sensitivity and specificity on-site were 91 and 97%, with 75-82 and 94-98% off-site. Evaluation was more sensitive on-site than off-site for detection of stenoses and occlusion, whereas specificity was similar. The CE MRA with 1.0-mol gadobutrol gave results comparable to those of i.a. DSA for the larger arteries of pelvis and thigh. Results for calf arteries were compromised by spatial resolution and technical limitations.

Frontiers in Aging Neuroscience

BackgroundFrailty in older adults has been associated with reduced brain health. However, structu... more BackgroundFrailty in older adults has been associated with reduced brain health. However, structural brain signatures of frailty remain understudied. Our aims were: (1) Explore associations between a frailty index (FI) and brain structure on magnetic resonance imaging (MRI). (2) Identify the most important FI features driving the associations.MethodsWe designed a cross-sectional observational study from a population-based study (The Irish Longitudinal Study on Aging: TILDA). Participants aged ≥50 years who underwent the wave 3 MRI sub-study were included. We measured cortex, basal ganglia, and each of the Desikan-Killiany regional volumes. Age-and sex-adjusted correlations were performed with a 32-item self-reported FI that included conditions commonly tested for frailty in research and clinical settings. A graph theory analysis of the network composed by each FI item and cortex volume was performed. White matter fiber integrity was quantified using diffusion tensor imaging (DTI).Re...

Neurobiology of Aging, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

American Journal of Case Reports, 2020

Patient: Male, 32-year-old Final Diagnosis: Granulomatous amebic encephalitis Symptoms: — Medicat... more Patient: Male, 32-year-old Final Diagnosis: Granulomatous amebic encephalitis Symptoms: — Medication:— Clinical Procedure: — Specialty: — Objective: Challenging differential diagnosis Background: Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. Case Report: We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. Conclusions: We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Neurobiology of Aging, 2021

This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist ci... more This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and physical activity (PA) with gray matter cerebral blood flow (CBF GM) in older adults. Cross-sectional data was used from the Irish Longitudinal Study on Ageing (n = 495, age 69.0 ±7.4 years, 52.1% female). Whole-brain CBF GM was quantified using arterial spin labeling MRI. Results from multivariable regression analysis revealed that an increase in BMI of 0.43 kg/m 2 , WHR of 0.01, or WC of 1.3 cm were associated with the same reduction in CBF GM as 1 year of advancing age. Participants overweight by BMI or with high WHR/WC reporting low/moderate PA had up to 3 ml/100g/min lower CBF GM (p ≤ .011); there was no significant reduction for those reporting high PA. Since PA could potentially moderate obesity/CBF associations, this may be a cost-effective and relatively easy way to help mitigate the negative impact of obesity in an older population, such as cerebral hypoperfusion, which is an early mechanism in vascular dementia and Alzheimer's disease.

NeuroImage, 2021

Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF... more Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF GM) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older. Background: Quantitative assessment of CBF GM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBF GM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion. Methods: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBF GM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations. Results: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBF GM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBF GM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = − 0.3, − 0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001). Conclusions: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBF GM measured at 3T using pCASL-MRI. Significant age-and sex-related differences exist in CBF GM .

JRSM Cardiovascular Disease, 2020

Introduction Orthostatic Hypotension (OH) is an abnormal drop in blood pressure (BP) that occurs ... more Introduction Orthostatic Hypotension (OH) is an abnormal drop in blood pressure (BP) that occurs following orthostatic challenge. OH is associated with increased risk of falls, cognitive impairment and death. White Matter Hyperintensities (WMH) on MR Brain are associated with vascular risk factors such as hypertension, diabetes and age. We examined whether extent White matter intensities were associated with presence of OH detected in a community dwelling population of older people. Methods Individuals from the MR sub-study of the Irish Longitudinal Study of Ageing underwent a 3 Tesla MR Brain scan to assess WMH severity (Schelten’s Score). The scans were performed during the Wave 3 TILDA health assessment phase when the subjects also underwent assessment for OH with an active stand protocol. Data was analysed for association between WMH and vascular risks and orthostatic change in BP 10 second intervals during the OH evaluation. Results 440 subjects were investigated; median age 72...

Irish Journal of Medical Science (1971 -), 2020

Background and aims A significant proportion of patients presenting to the Emergency Department w... more Background and aims A significant proportion of patients presenting to the Emergency Department with gastrointestinal symptoms that result in cross-sectional imaging receive a radiological diagnosis of colitis. We aimed to review the characteristics, outcomes, and final diagnoses of new emergency department presentations with colitis diagnosed on cross-sectional imaging. Methods A radiology database was interrogated to identify patients admitted from the Emergency Department of St James's Hospital whose cross-sectional imaging demonstrated colitis. Baseline demographic data, information on inpatient investigations, final diagnoses, and outcomes were recorded. Adverse outcomes were defined as a requirement for surgery, intensive care unit (ICU) stay, or mortality Results A total of 118 patients, 67% female, were identified with a median age of 64 years (range 16.9-101.2). Median (range) admission duration was 10 days (1-241). Final colitis diagnoses were infectious (28%), undefined (27%), reactive (18%), inflammatory bowel disease (11%), ischaemic (9%), chemotherapy-associated (3%), diverticular (3%), and medication-associated (1%). Colonic perforation, colectomy, and mortality occurred in 1%, 5%, and 13% of the cohort respectively. On univariate analysis, low haemoglobin, low albumin, high lactate, and male gender were associated with adverse outcomes with the following odds ratios (OR) and 95% confidence intervals (95%CI) were low haemoglobin 1.

Journal of Cerebral Blood Flow & Metabolism, 2019

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet bio... more The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation. We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray–Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as ‘MES+ve’ or ‘MES-ve’. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets. Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (...

International Journal of Epidemiology, 2018

Irish Journal of Medical Science (1971 -), 2015

Background Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainste... more Background Nystagmus in patients with multiple sclerosis (MS) is generally attributed to brainstem disease. Lesions in other regions may result in nystagmus. The identification of these other sites is enhanced by using 3-Tesla magnetic resonance imaging (3TMRI) due to increased signal-to-noise ratio. Objective We sought to evaluate the distribution of structural lesions and disruption of tracts in patients with horizontal nystagmus secondary to MS using 3TMRI. Methods Twenty-four patients (20 women, 4 men; age range 26-55 years) with horizontal nystagmus secondary to MS underwent 3TMRI brain scans; and 18 patients had diffusion tensor imaging (DTI) for tractography. Results Nystagmus was bidirectional in 11, right-sided in 6 and left-sided in 7. We identified 194 lesions in 20 regions within the neural integrator circuit in 24 patients; 140 were within the cortex and 54 were within the brainstem. Only two patients had no lesions in the cortex, and 9 had no lesions in the brainstem. There was no relationship between side of lesion and direction of nystagmus. Thirteen of 18 (72 %) had tract disruption with fractional anisotropy (FA) values below 0.2. FA was significantly lower in bidirectional compared to unidirectional nystagmus (p = 0.006). Conclusion In MS patients with horizontal nystagmus, lesions in all cortical eye fields and their descending connections were evident. Technical improvements in tractography may help identify the specific site(s) resulting in nystagmus in MS.

Physics in medicine and biology, Oct 3, 2016

A novel anthropomorphic flow phantom device has been developed, which can be used for quantitativ... more A novel anthropomorphic flow phantom device has been developed, which can be used for quantitatively assessing the ability of magnetic resonance imaging (MRI) scanners to accurately measure signal/concentration time-intensity curves (CTCs) associated with dynamic contrast-enhanced (DCE) MRI. Modelling of the complex pharmacokinetics of contrast agents as they perfuse through the tumour capillary network has shown great promise for cancer diagnosis and therapy monitoring. However, clinical adoption has been hindered by methodological problems, resulting in a lack of consensus regarding the most appropriate acquisition and modelling methodology to use and a consequent wide discrepancy in published data. A heretofore overlooked source of such discrepancy may arise from measurement errors of tumour CTCs deriving from the imaging pulse sequence itself, while the effects on the fidelity of CTC measurement of using rapidly-accelerated sequences such as parallel imaging and compressed sensi...