Background
The potential role of the amygdala for neuropsychiatric symptoms (NPS) in dementia is not well known, especially in dementia with Lewy bodies (DLB). Cross‐sectional studies have proposed ...the associations between amygdala volume and NPS in Alzheimer’s Disease (AD). However, less is known about the association between amygdala volume and longitudinal trajectories of NPS. We aimed to analyze the association between amygdala volume and the longitudinal trajectories of NPS in AD and DLB.
Method
89 patients with mild dementia were included (AD = 55; DLB =34) in this secondary analysis of a longitudinal cohort study. Baseline amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi‐automatic method (Freesurfer 6.0). NPS were assessed annually over five years with the Neuropsychiatric Inventory (NPI) frequency × severity item‐scores. NPI item‐scores ≥ 4 were considered clinically relevant symptoms. Mixed‐effects logistic regression models were conducted in the whole sample and then in AD and DLB separately. Amygdala volume was included as a predictor of each NPS (i.e. NPI item‐score ≥ 4) over time. The models were adjusted for key demographic variables and diagnostic, as well as for center of sMRI acquisition and cognition.
Result
The cohort characteristics are shown in Table 1. Intracranial volume‐normalized amygdala volumes were comparable between AD and DLB patients. After correcting adjusted models for multiple testing, a lower odds of apathy scores ≥ 4 over time was found in patients with larger amygdala volume at baseline (OR:0.36; 95% CI: 0.21 – 0.64; p < 0.001; FDR = 0.002), with no significant effects of diagnostic (OR: 1.11; 95%CI: 0.56 – 2.17; p = 0.769; FDR = 0.846), Figure 1. The subgroup analyses showed significant results for apathy in both DLB and AD: (DLB (OR: 0.37; 95% CI: 0.16 – 0.87; p = 0.023) and AD (OR: 0.35; 95% CI: 0.15 – 0.79; p = 0.012).
Conclusion
Smaller amygdala volumes in people with mild dementia were associated with a higher risk of clinically relevant apathy, in both AD and DLB patients, during the 5 years study period. This association between apathy and amygdala might reflect damage in circuits underlying behavioral and cognitive avoidance.
During four separate Israeli military attacks on Gaza (2006, 2009, 2012, and 2014), about 4000 Palestinians were killed and more than 17 000 injured (412 killed and 1264 injured in 2006; 1383 killed ...and more than 5300 injured in 2009; 130 killed and 1399 injured in 2012; and 2251 killed and 11 231 injured in 2014). An unknown number of people had traumatic amputations of one or more extremities. Use of unmanned Israeli drones for surveillance and armed attacks on Gaza was evident, but exact figures on numbers of drone strikes on Gaza are not available. The aim of this study was to explore the medical consequences of strikes on Gaza with different weapons, including drones.
We studied a cohort of civilians in the Gaza Strip who had one of more traumatic limb amputation during the Israeli military attacks between 2006 and 2016. The study was done at The Artificial Limb and Polio Center (ALPC) in the Gaza Strip where most patients are treated and trained after amputation. We used standardised forms and validated instruments to record date and mechanism of injury, self-assessed health, socioeconomic status, anatomical location and length of amputation, comorbidity, and the results of a detailed clinical examination.
The studied cohort consisted of 254 Paletinian civilians (234 92% men, 20 8% women, and 43 17% children aged 18 years and younger) with traumatic amputations caused by different weapons. 216 (85%) people had amputations proximal to wrist or ankle, 131 (52%) patients had more than one major amputation or an amputation above the knee, or both, and 136 (54%) people were injured in attacks with Israeli drones, including eight (40%) of the women. The most severe amputations were caused by drone attacks (p=0·0001). Extremity injuries after drone attacks led to immediate amputation more often than with other weapons (p=0·014). Patients injured during cease-fire periods were younger than patients injured during periods of declared Israeli military operations (p=0·0001).
Weapons fired on the Gaza Strip from Israeli drones caused severe injuries in surviving Palestinian civilians. Drone-fired missiles resulted in major amputations in almost all victims who had limb losses. Substantially more severe injuries were inflicted by the drone-launched explosives than by other weapons used during the Gaza War. Traumatic amputations caused by drones were often immediately complete. One limitation of our study is that it does not elucidate injury patterns in victims with fatal injuries.
None.
Altered plasma amino acid levels have been implicated as markers of risk for incident type 2 diabetes; however, amino acids are also related to established diabetes risk factors. Therefore, potential ...for confounding and the impact from competing risks require evaluation.
We prospectively followed 2,519 individuals with coronary artery disease but without diabetes. Mixed Gaussian modeling identified potential for confounding. Confounding, defined as a change in effect estimate (≥10%), was investigated by comparing amino acid-incident diabetes risk in a Cox model containing age and sex with that in models adjusted for potential confounders (BMI, estimated glomerular filtration rate, HDL cholesterol, triacylglycerol, C-reactive protein), which were further adjusted for plasma glucose, competing risks, and multiple comparisons (false discovery rate = 0.05, Benjamini-Hochberg method). Finally, component-wise likelihood-based boosting analysis including amino acids and confounders was performed and adjusted for competing risks in order to identify an optimal submodel for predicting incident diabetes.
The mean age of the source population was 61.9 years; 72% were men. During a median follow-up of 10.3 years, 267 incident cases of diabetes were identified. In age- and sex-adjusted models, several amino acids, including the branched-chain amino acids, significantly predicted incident diabetes. Adjustment for confounders, however, attenuated associations. Further adjustment for glucose and multiple comparisons rendered only arginine significant (hazard ratio/1 SD 1.21 95% CI 1.07-1.37). The optimal submodel included arginine and asparagine.
Adjustment for relevant clinical factors attenuated the amino acid-incident diabetes risk. Although these findings do not preclude the potential pathogenic role of other amino acids, they suggest that plasma arginine is independently associated with incident diabetes. Both arginine and asparagine were identified in an optimal model for predicting new-onset type 2 diabetes.
Background: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. ...Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive. Methods: We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality. Results: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 1.78, 2.87, p
Abstract
Introduction
Functionality is one of the most important markers of wellbeing in older adults. People with dementia lose functionality mainly because of cognitive impairment. However, little ...has been outlined regarding the independent association of Neuropsychiatric symptoms (NPS) on functional decline in this population, especially in those diagnosed with Lewy body dementia (LBD). The aim of our work is to study the association of NPS at time of dementia diagnosis and 5‐year longitudinal course with the 5 years’ trajectory of functional decline in people with Alzheimer´s disease (AD) and LBD.
Methods
This is a secondary analysis of the Dementia Study of Western Norway (DemWest) including a total of 196 patients with newly diagnosed AD (n=111) and LBD (n=85). Baseline information on NPS was obtained using the Neuropsychiatric Inventory (NPI), and activities of daily living (ADL) was assessed yearly during five years using the rapid disability rating scale (RDRS). The longitudinal functional trajectories were analyzed using linear mixed modeling, adjusting by Age, cognition, sex and comorbidity.
Results
Total NPI score at diagnosis was associated with functional decline for AD (Est 0.007 SE 0.002 p‐value 0.0014) but not for LBD (Est 0.002 SE 0.003 p‐value 0.4258). NPI score longitudinal course was associated with the functional decline trajectory in AD (Est 0.004 SE 0.001 p‐value 0.0002) and LBD (Est 0.005 SE 0.002 p‐value 0.0070).
Conclusion
NPS independently predicted the rate of functional decline in people with AD and LBD despite their cognitive status. These results highlight the relevance of early detection and intervention of NPS, which may also reduce functional decline.
Introduction
Functionality is one of the most important markers of wellbeing in older adults. People with dementia lose functionality mainly because of cognitive impairment. However, little has been ...outlined regarding the independent association of Neuropsychiatric symptoms (NPS) on functional decline in this population, especially in those diagnosed with Lewy body dementia (LBD). The aim of our work is to study the association of NPS at time of dementia diagnosis and 5‐year longitudinal course with the 5 years’ trajectory of functional decline in people with Alzheimer´s disease (AD) and LBD.
Methods
This is a secondary analysis of the Dementia Study of Western Norway (DemWest) including a total of 196 patients with newly diagnosed AD (n=111) and LBD (n=85). Baseline information on NPS was obtained using the Neuropsychiatric Inventory (NPI), and activities of daily living (ADL) was assessed yearly during five years using the rapid disability rating scale (RDRS). The longitudinal functional trajectories were analyzed using linear mixed modeling, adjusting by Age, cognition, sex and comorbidity.
Results
Total NPI score at diagnosis was associated with functional decline for AD (Est 0.007 SE 0.002 p‐value 0.0014) but not for LBD (Est 0.002 SE 0.003 p‐value 0.4258). NPI score longitudinal course was associated with the functional decline trajectory in AD (Est 0.004 SE 0.001 p‐value 0.0002) and LBD (Est 0.005 SE 0.002 p‐value 0.0070).
Conclusion
NPS independently predicted the rate of functional decline in people with AD and LBD despite their cognitive status. These results highlight the relevance of early detection and intervention of NPS, which may also reduce functional decline.
Anthocyanins may protect against cardiovascular related cognitive decline and dementia.
Open-label study to measure changes in serum lipids, glucose, glycosylated hemoglobin (HbA1c), and markers of ...inflammation after anthocyanin supplementation in people with increased risk of dementia. As a secondary endpoint we examined potential changes in a battery of cognitive test in the anthocyanin group (AG). A total of 27 individuals with mild cognitive impairment (MCI) (
= 8) or stable non-obstructive coronary artery disease (CAD) (
= 19) consumed two Medox
capsules, each containing 80 mg of natural purified anthocyanins, twice daily for 16 weeks. They provided blood samples and performed a short battery of cognitive tests. Twenty healthy normal controls (NC) (
= 20) provided blood samples, but did not receive any intervention and did not perform cognitive tests.
There was a significant difference between groups for CCL-5/RANTES regulated on activation, normal T-cell expressed and secreted (RANTES). In addition, total cholesterol and triglycerides were significantly increased in the AG. Improvements in memory and executive test scores were observed. No adverse effects were reported.
The results of this pilot study were largely inconclusive with regard to the potential protective effects of anthocyanin supplementation. However, anthocyanins were well tolerated, and compliance was high. Larger, placebo-controlled studies to explore the potential effects of anthocyanins on dementia risk are encouraged.
www.ClinicalTrials.gov, identifier NCT02409446.
Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and ...neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.
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