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Objective: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline.Methods: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA.Results: PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score.Conclusions: Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia. [ABSTRACT FROM AUTHOR]

BackgroundLate-life depression (LLD) is associated with a decline in physical activity. Typically this is assessed by self-report questionnaires and, more recently, with actigraphy. We sought to explore the utility of a bespoke activity monitor to characterize activity profiles in LLD more precisely.MethodThe activity monitor was worn for 7 days by 29 adults with LLD and 30 healthy controls. Subjects underwent neuropsychological assessment and quality of life (QoL) (36-item Short-Form Health Survey) and activities of daily living (ADL) scales (Instrumental Activities of Daily Living Scale) were administered.ResultsPhysical activity was significantly reduced in LLD compared with controls (t = 3.63, p < 0.001), primarily in the morning. LLD subjects showed slower fine motor movements (t = 3.49, p < 0.001). In LLD patients, activity reductions were related to reduced ADL (r = 0.61, p < 0.001), lower QoL (r = 0.65, p < 0.001), associative learning (r = 0.40, p = 0.036), and higher Montgomery–Åsberg Depression Rating Scale score (r = −0.37, p < 0.05).ConclusionsPatients with LLD had a significant reduction in general physical activity compared with healthy controls. Assessment of specific activity parameters further revealed the correlates of impairments associated with LLD. Our study suggests that novel wearable technology has the potential to provide an objective way of monitoring real-world function. [ABSTRACT FROM PUBLISHER]

Background: Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear.Aims: To investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders.Method: In a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year.Results: Using logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01).Conclusions: White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life. [ABSTRACT FROM AUTHOR]

One of the most characteristic changes in Alzheimer's disease (AD) is a deficit in cortical cholinergic neurotransmission and associated receptor changes. To investigate differences in the distribution of M1/M4 receptors using (R, R) 123I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in patients with mild/moderate AD and agematched controls. Also, to compare 123I-QNB uptake to the corresponding changes in regional cerebral blood flow (rCBF) in the same subjects. Forty two subjects (18 AD and 24 healthy elderly controls) underwent 123IQNB and perfusion 99mTc-exametazime SPECT scanning. Image analysis was performed using statistical parametric mapping (SPM99) following intensity normalisation of each image to its corresponding mean whole brain uptake. Group differences and correlations were assessed using two sample t-tests and linear regression respectively. Significant reductions in 123I-QNB uptake were observed in regions of the frontal rectal gyrus, right parahippocampal gyrus, left hippocampus and areas of the left temporal lobe in AD compared to controls (height threshold of p ≤ 0.001 uncorrected). Such regions were also associated with marked deficits in rCBF. No significant correlations were identified between imaging data and clinical variables. Functional impairment as measured by rCBF is more widespread than changes in M1/M4 receptor density in mild/moderate AD, where there was little or no selective loss of M1/M4 receptors in these patients that was greater than the general functional deficits shown on rCBF scans. [ABSTRACT FROM AUTHOR]

Background: Brain perfusion deficits have been reported previously in subjects with Parkinson's disease in comparison with healthy controls.Objective: To carry out a longitudinal study of perfusion in patients with Parkinson's disease and controls to find areas showing a reduction in perfusion over one year.Methods: Two HMPAO cerebral perfusion scans were acquired one year apart in 30 subjects with Parkinson's disease (mean (SD) age, 76 (5) years) and 34 healthy comparison subjects (76 (7) years). Scans were normalised to the mean intensity in the cerebellum.Results: Using SPM99 within groups to investigate regions that showed a decrease in perfusion between scans, it was found that in Parkinson's disease subjects but not controls there was a significant cluster in the frontal lobe (Brodmann area 10) where perfusion decreased over the year.Conclusions: The progressive frontal perfusion deficits in Parkinson's disease are consistent with results from previous structural and neuropsychological studies suggesting frontal lobe involvement and executive dysfunction even in early Parkinson's disease. [ABSTRACT FROM AUTHOR]

Liver and skeletal muscle triglyceride stores are elevated in type 2 diabetes and correlate with insulin resistance. As postprandial handling of dietary fat may be a critical determinant of tissue triglyceride levels, we quantified postprandial fat storage in normal and type 2 diabetes subjects. Healthy volunteers (n = 8) and diet-controlled type 2 diabetes subjects (n = 12) were studied using a novel 13C magnetic resonance spectroscopy protocol to measure the postprandial increment in liver and skeletal muscle triglyceride following ingestion of 13C-labeled fatty acids given with a standard mixed meal. The postprandial increment in hepatic triglyceride was rapid in both groups (peak increment controls: +7.3 ± 1.5 mmol/l at 6 h, P = 0.002; peak increment diabetics: +10.8 ± 3.4 mmol/l at 4 h, P = 0.009). The mean postprandial incremental AUC of hepatic 13C enrichment between the first and second meals (0 and 4 h) was significantly higher in the diabetes group (6.1 ± 1.4 vs. 1.7 ± 0.6 mmol·l-1·h-1, P = 0.019). Postprandial increment in skeletal muscle triglyceride in the control group was small compared with the diabetic group, the mean 24-h postprandial incremental AUC being 0.2 ± 0.3 vs. 1.7 ± 0.4 mmol·l-1·h-1 (P = 0.009). We conclude that the postprandial uptake of fatty acids by liver and skeletal muscle is increased in type 2 diabetes and may underlie the elevated tissue triglyceride stores and consequent insulin resistance. [ABSTRACT FROM AUTHOR]

Introduction Patients with Lewy body dementia typically suffer from symptoms of parkinsonism, visual hallucinations and fluctuating cognition with a pronounced attentional impairment. However, the underlying network dysfunctions of the latter are unclear, which obstructs applying targeted cognitive therapies. Therefore we aimed to study network interactions during attentional processing in Lewy body dementia and compare them with Alzheimer”s disease and healthy controls. Subjects and methods 30 patients with Lewy body dementia, 20 patients with Alzheimer’s disease and 21 matched healthy controls performed a modified version of the Attention Network Test within an MRI scanner. They were asked to press a button in reaction to the majority direction of four displayed arrows which could either point into the same direction (congruent condition) or with one arrow pointing to the opposite site (incongruent condition). The resulting event-related fMRI data were preprocessed and then decomposed into functional networks using an Independent Component Analysis. We visually chose five networks (executive network, ventral and dorsal attentional network, default mode network) for an in-depth analysis of their interactions. Then we extracted timeseries of each network applying dual regression. Beta estimates were calculated by performing GLMs using each event as a separate regressor. They were grouped together as beta series for similar events and correlated with each other. Networks with positive correlations were assumed to have similar patterns of inter-trial variability as an indication of functional connectivity. These network interactions could be then compared between groups. Results We found reduced functional connectivity of ventral and dorsal attention networks in patients with Lewy Body dementia in contrast to patients with Alzheimer’s disease and healthy subjects, particularly during incongruent trials. Contrarily, in Alzheimer”s disease, we could observe increased connectivity between the posterior part of the default mode network and the dorsal attention network, which was also most prominent during incongruent trials. Discussion We assume that the reduced connectivity of attention networks in Lewy body dementia is a result of a disturbed bottom-up transfer from ventral attention networks, whereas the hyperconnectivity between the default mode network and the dorsal attention network in Alzheimer”s disease might constitute a compensational mechanism to overcome default network dysfunction or relate to an inefficient transition of the default mode network from a resting state to a task-related state. In brief, dementia syndromes can be composed of both hyper- and hypoconnectivity of brain networks, depending on the interplay between given neural resources, cognitive requirements and also the underlying pathology. [ABSTRACT FROM AUTHOR]

The Health and Social Care Awards were launched to celebrate the excellent or innovative work of front line healthcare staff. This article previews the ninth award ceremony next year and highlights two of the winners from this year. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2) recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32]) and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86]) than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]). A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]). Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that contribute to metabolic status in obese individuals.

Introduction: Cerebral microbleeds are small (2-10mm) hypointensities visualised on T2*-weighted MRI scans. They are considered small vessel disease markers and are associated with stroke and Alzheimer's disease severity; their clinical significance in the general older population is poorly understood. We aimed to determine: the prevalence of microbleeds in a community-dwelling cohort of people age >75 years and if microbleed presence was associated with cognitive or physical function.Methods: Subjects were recruited from a longitudinal community cohort examining predictors of cognitive impairment. Participants underwent: detailed cognitive testing (MMSE, CAMCOG-R, reaction times), Tinetti assessment of gait and balance and a MRI brain scan. T2*-weighted scans were reviewed independently for microbleeds by two authors (KEM & CMcD) using the Microbleed Anatomical Rating Scale criteria. Inter-rater disagreements were decided by a third author (MF.)Results: Fifty-three subjects underwent MRI scanning; one was excluded due to poor scan quality leaving a cohort of 52 (median age (IQR) 79.0 (76.3-83.8); 57.7% male.) Ten subjects had microbleed(s); most (n = 7) displayed a single microbleed. Comparing cognitive function and Tinetti scores in microbleed–negative and -positive groups did not reveal any significant differences (Table 1).Variablemicrobleed negative (n = 42) median (IQR)microbleed positive (n = 10) median (IQR)PAge78.5 (76.0-83.3)80.5 (77.3-85.3)0.568MMSE28 (26-29)29 (26-29)0.790CAMCOG-R94 (91-98)97 (90-99)0.730Power of attention (msec)1640 (1510-1800)1660 (1420-1760)0.810Tinetti balance24 (22-25)23.5 (21.5-24)0.284Tinetti gait9 (4.5-9)8 (4-9)0.639Conclusions: Microbleeds were found infrequently and in low numbers in our cohort and were not associated with cognitive or physical function. This is in keeping with findings from 2 similar studies in community cohorts. It is likely that as with other small vessel disease markers that there is a threshold effect with small numbers of microbleeds constituting incidental findings. [ABSTRACT FROM AUTHOR]