Examining the Impact of Socioeconomic Position Across the Life Course on Cognitive Function and Brain Structure in Healthy Aging.

This study explores the relationship of life-course intergenerational social mobility with cognitive function and brain structure in older adults using Diagonal Reference Models. Data from the Irish Longitudinal Study on Ageing, a population-based cohort of adults aged 50 years and older (N = 4 620 participants; mean age: 66.1; standard deviation: 9.1; 55% female) was used for analysis. Brain magnetic resonance imaging data were available for 464 participants. Social mobility was characterized as the difference between childhood socioeconomic position (SEP; ie, father's occupation) and adulthood SEP (ie, own occupation). The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), cortical thickness, and total gray matter volume (GMV) served as global cognitive and brain measures. Exploratory analyses included the volumes of the ventromedial prefrontal cortex (vmPFC), anterior cingulate (AC), hippocampus, and amygdala. A social gradient in cognitive function was observed among the intergenerationally stable; brain structure was not as clearly socially patterned. Adulthood SEP was significantly associated with MoCA (weight = 0.76; p < .001), MMSE (weight = 0.91; p < .001), GMV (weight = 0.77; p = .002), and AC volume (weight = 0.76; p < .001), whereas childhood SEP was associated with vmPFC volume (weight = 1.00; p = .003). There was no independent association of social mobility with any of the outcomes. Together our results suggest that both childhood and adulthood SEP are important in shaping later-life brain health, but that adulthood SEP predominates in terms of its influence. This is potentially an important insight as it suggests that brain health may be modifiable if socioeconomic circumstances change.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

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.

Simultaneous assessment of plaque morphology, cerebral micro-embolic signal status and platelet biomarkers in patients with recently symptomatic and asymptomatic carotid stenosis.

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 (25 vs. 30; P = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 109/L), neutrophil-platelet (3.3 vs. 2.7%), monocyte-platelet (6.3 vs. 4.55%) and lymphocyte-platelet complexes (2.91 vs. 2.53%) than 'asymptomatic patients with GSM-echodense plaques' (P ≤ 0.03).Recently, symptomatic carotid stenosis patients with 'GSM-echodense plaques' have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

Donepezil impairs memory in healthy older subjects: behavioural, EEG and simultaneous EEG/fMRI biomarkers.

Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short- and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week follow-ups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise neuroanatomical origins of EEG drug markers using simultaneous EEG/fMRI. The results of this study may be useful for evaluating novel drugs for cognitive enhancement.

The validity of Rehabilitative Ultrasound Imaging for measurement of trapezius muscle thickness.

The purpose of the study was to establish the validity of Rehabilitative Ultrasound Imaging (RUSI) against Magnetic Resonance Imaging (MRI) for measuring trapezius muscle thickness. Participants were asymptomatic subjects recruited from Trinity College Dublin and associated teaching hospitals. Four MRI axial slices were made through each of the C6, T1, T5 and T8 spinous processes, with the subject supine. RUSI was performed immediately after MRI at the same vertebral levels, with the subject prone. Linear measurements of trapezius muscle thickness were made off-line on both the MRI and Ultrasound scans, in three regions: lower, middle and upper trapezius. Bland and Altman limits of agreement and Pearson's correlation coefficient were used to analyse the relationship between thickness measures taken from MRI and RUSI. Eighteen subjects (9 women) participated, (age-range 21-42 years). Results demonstrated good agreement between MRI and RUSI measurements of the lower trapezius muscle at T8 (r=0.77) and moderate agreement at T5, (r=0.62). Results were poor for the middle (T1) and upper (C6) trapezius muscles, (r=-0.22 to 0.52) but may be explained by differences in both positioning and imaging planes between the 2 modalities. It was concluded that RUSI is a valid method of measuring lower trapezius muscle thickness.

Evaluation of suspected renal colic with noncontrast CT in the emergency department: a single institution study.

BACKGROUND AND PURPOSE: Noncontrast CT (NCCT) has become the standard Imaging study in the emergency department (ED) diagnosis of nephro- and ureterolithiasis. We undertook to audit the results from the first 500 NCCTs performed for patients presenting to the ED with suspected renal colic. PATIENTS AND METHODS: In a retrospective study at one institution from October 2003 to February 2006, 500 patients with suspected stone disease were investigated. In the study, NCCT findings, patient clinical records, and urinary microscopy results were evaluated for 166 women and 334 men. RESULTS: Renal or ureteral calculi were identified in 279 (56%) of NCCTs performed. Of the 500, 112 (19%) NCCTs performed identified unexpected intra-abdominal pathology. When the findings deemed to be of low clinical significance were excluded, the number of scans with additional pathology amounted to 67 (13%). These included vascular emergencies, new cancer diagnoses, and gastrointestinal conditions. CONCLUSIONS: The variety of diagnoses found unexpectedly on the NCCT that alter a patient's treatment demonstrates the pivotal role of NCCT in the triage of these patients rapidly toward optimal therapy. The rapid acquisition time of NCCT has enabled definitive ED patient diagnosis and less bed occupancy for clinically insignificant calculi.

Solitary subcutaneous metastatic deposit from hepatocellular carcinoma.

Hepatocellular carcinoma is the most common primary tumour of the liver. Metastasis is frequent in these aggressive tumours and is commonly to the lungs, regional lymph nodes, or bone. Metastasis as a discrete subcutaneous nodule has not been described before. We report a case of hepatocellular carcinoma with a solitary subcutaneous metastatic deposit identified 18 months after the initial hepatic surgery.