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Alzheimer’s disease (AD) pathophysiology, including β-amyloid (Aβ), can be appreciated with molecular PET imaging. Among older adults, the distribution of Aβ standard uptake value ratios (SUVR) is typically bimodal and a diagnostic cut is applied to define those who are amyloid ‘positive’ and ‘negative’. However, it is unclear whether the dynamic range of SUVRs in amyloid positive and negative individuals is meaningful and associated with cognition. Previous work by Insel and colleagues (2020) used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial to demonstrate subtle associations between a cortical summary SUVR and cognition, particularly on the Free and Cued Selective Reminding Test (FCSRT). We followed up this study to determine the extent to which regional SUVR is associated with performance on the FCSRT in amyloid positive and negative participants screened for participation in the A4 study.
Participants and Methods:
We accessed regional Aβ SUVR, including anterior cingulate, posterior cingulate, parietal, precuneus, temporal, and medial/orbital frontal regions, along with FCSRT15 and demographic data from 4492 A4 participants at screening. Participants were coded as amyloid positive (n=1329; 30%) or amyloid negative (n=3169; 70%) based on a summary SUVR of greater than or equal to 1.15. We used separate general linear models to examine the association of total or regional SUVR, amyloid positivity status, and the interaction of SUVR and amyloid status with FCSRT scores. We compared model fits across regions with the Akaike Information Criterion (AIC). We ran post hoc correlational analyses examining the relationship between SUVR and FCSRT scores stratified by amyloid status in the case of significant interactions. Results were similar with and without demographic adjustment.
Results:
There was a significant interaction of summary and all regional SUVR with FCSRT scores in addition to main effects of amyloid positivity. In all models, there were small negative associations between SUVR and memory in amyloid positive individuals. For amyloid negative individuals, there was a significant and very small negative association between SUVR and FCSRT scores only in the parietal lobes and precuneus regions. Model fits were generally similar across the different analyses.
Conclusions:
In this sample of individuals screened for a secondary prevention trial of AD, there were consistent associations between Aβ SUVR in all regions and memory for those considered amyloid positive. However, for individuals considered amyloid negative, there were only very small associations between SUVR and memory in parietal and precuneus regions. We conclude that the dynamic range of amyloid may be relevant among those with diagnostic evidence of amyloidosis, but that subtle Aβ accumulation in posterior regions may relate to declining memory in “subthreshold” states.
Lakes in the semiarid Southern Interior Plateau of British Columbia, Canada are vulnerable to future climate-driven changes in water quantity and quality. However, few long-term monitoring records exist to assess the effects of varying hydroclimate conditions on lake function. We present a high-resolution multiproxy paleolimnological record containing subfossil diatoms, μXRF via ITRAX, and chlorophyll-a that spans the past 1800 years from Roche Lake in south-central British Columbia. Generalized additive models indicate that the diatom assemblages were associated with changes in lake level and the accompanying effects of atmospheric forcing on lake thermal structure, and that these forcing mechanisms had a weak relationship with primary production. We infer two pronounced arid periods between ca. AD 600–950 and ca. AD 1730–1950 that correspond to evidence of reduced lake mixing and enhanced anoxia, but variable patterns in primary production. Synthesis of regional proxy records suggests that inferences of moist but possibly warm conditions during the Medieval Climate Anomaly may have occurred because of a complex interaction between prolonged La Niña-like conditions and higher radiative forcing. Overall, lakes in this region are sensitive to changes in hydroclimate generated by interactions between external forcing and Pacific Ocean–atmosphere processes, and the resulting changes in aridity may have potentially negative consequences on salmonid habitat.
The principle and practice of pro bono, or volunteer legal services for the poor and other marginalized groups, is an increasingly important feature of justice systems around the world. Pro bono initiatives now exist in more than eighty countries – including Colombia, Portugal, Nigeria, and Singapore – and the list keeps growing. Covering the spread of pro bono across five continents, this book provides a unique data set permitting the first-ever comparative analysis of pro bono's growing role in the access to justice movement. The contributors are leading experts from around the world, whose chapters examine both the internal roots of and global influences on pro bono in transnational context. Global Pro Bono explores the dramatically expanding geographical and political reach of pro bono: documenting its essential contribution to bringing more justice to those on the margins, while underscoring its complex and contested meaning in different parts of the world.
The principle and practice of pro bono – volunteer legal services for poor and other marginalized groups – is an increasingly important feature of justice systems around the world. A quarter century ago, organized pro bono programs were a rarity in the United States and virtually nonexistent elsewhere. Now, in contrast, pro bono has become widely diffused and institutionally central in a growing number of countries throughout the Global North and Global South. In a sign of pro bono’s increasing international profile, PILNet (the Network for Public Interest Law), a key sponsor of the global pro bono movement, has hosted Pro Bono Forums across continents (ten in Europe and five in Asia), bringing together law firm pro bono coordinators, civil society partners, and representatives from more than fifty pro bono organizations in countries as diverse as Indonesia and Italy. In 2013, the Global Pro Bono Network was founded as a consortium of pro bono intermediaries and now includes 52 organizations in 34 countries. A 2016 survey of large-firm pro bono, covering 64,500 lawyers from 130 law firms in 75 countries, showed lawyers contributed 2.5 million pro bono hours over a 12-month period, with an annual average of 39.2 hours per lawyer. Once confined to the professional margins, pro bono now occupies a central position in the global access-to-justice movement.
Inadequate nutrient intakes have been linked with poor dentition in older adults. The aim of this study was to investigate the associations between the composition of functional tooth units (FTU) and nutrient intakes in older men.
Design:
A cross-sectional study with a standardised validated diet history assessment and comprehensive oral health assessments. FTU were categorised by dentition type: (i) Group A (Natural FTU Only), (ii) Group B (Natural and Replaced FTU) and (iii) Group C (No Natural FTU). Attainment of nutrient reference values (NRV) for sixteen micronutrients was incorporated into a micronutrient risk variable, dichotomised ‘good’ (≥ 12) or ‘poor’ (≤ 11), and for seven macronutrients into a macronutrient risk variable, dichotomised ‘good’ (≥ 5) or ‘poor’ (≤ 4).
Setting:
Subjects selected from the local Sydney geographical areas.
Participants:
Community-dwelling older men (n 608).
Results:
32 % (n 197) of participants were categorised as Group A, 27 % (n 167) as Group B and 40 % (n 244) as Group C. In adjusted logistic regression analysis, being in Group C, compared with Group A, was associated with intakes below NRV recommendations for fibre (OR: 2·30, 95 % CI 1·30, 4·05). Adjusted analysis also showed that men in Group C, compared with Group A, were more likely to have poor intake of macronutrients (OR: 2·00, 95 % CI 1·01, 3·94).
Conclusions:
Our study shows statistically significant associations between the composition of FTU and poor macronutrient intakes. Maintaining natural pairs of occluding FTU may be important for attaining adequate nutrient intakes in older men.
We identified quality indicators (QIs) for care during transitions of older persons (≥ 65 years of age). Through systematic literature review, we catalogued QIs related to older persons’ transitions in care among continuing care settings and between continuing care and acute care settings and back. Through two Delphi survey rounds, experts ranked relevance, feasibility, and scientific soundness of QIs. A steering committee reviewed QIs for their feasible capture in Canadian administrative databases. Our search yielded 326 QIs from 53 sources. A final set of 38 feasible indicators to measure in current practice was included. The highest proportions of indicators were for the emergency department (47%) and the Institute of Medicine (IOM) quality domain of effectiveness (39.5%). Most feasible indicators were outcome indicators. Our work highlights a lack of standardized transition QI development in practice, and the limitations of current free-text documentation systems in capturing relevant and consistent data.
Transitions for older persons from long-term care (LTC) to the emergency department (ED) and back, can result in adverse events. Effective communication among care settings is required to ensure continuity of care. We implemented a standardized form for improving consistency of documentation during LTC to ED transitions of residents 65 years of age or older, via emergency medical services (EMS), and back. Data on form use and form completion were collected through chart review. Practitioners’ perspectives were collected using surveys. The form was used in 90/244 (37%) LTC to ED transitions, with large variation in data element completion. EMS and ED reported improved identification of resident information. LTC personnel preferred usual practice to the new form and twice reported prioritizing form completion before calling 911. To minimize risk of harmful unintended consequences, communication forms should be implemented as part of broader quality improvement programs, rather than as stand-alone interventions.
To assess the associations between nutrient intake and dietary patterns with different sarcopenia definitions in older men.
Design:
Cross-sectional study.
Setting:
Sarcopenia was defined using the Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP) and the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Dietary adequacy of fourteen nutrients was assessed by comparing participants’ intakes with the Nutrient Reference Values (NRV). Attainment of NRV for nutrients was incorporated into a variable ‘poor’ (meeting ≤ 9) v. ‘good’ (meeting ≥ 10) using the cut-point method. Also, two different dietary patterns, monounsaturated:saturated fat and n-6:n-3 fatty acids ratio and individual nutrients were used as predictor variables.
Participants:
A total of 794 men aged ≥75 years participated in this study.
Results:
The prevalence of sarcopenia by the FNIH, EWGSOP and EWGSOP2 definitions was 12·9 %, 12·9 % and 19·6 %, respectively. With the adjustment, poor nutrient intake was significantly associated with FNIH-defined sarcopenia (OR: 2·07 (95 % CI 1·16, 3·67)), but not with EWGSOP and EWGSPOP2 definitions. The lowest and second-lowest quartiles of protein, Mg and Ca and the lowest quartiles of n-6 PUFA and n-3 PUFA intakes were significantly associated with FNIH-defined sarcopenia. Each unit decrease in n-6:n-3 ratio was significantly associated with a 9 % increased risk of FNIH-defined sarcopenia (OR: 1·09 (95 % CI 1·04, 1·16)).
Conclusions:
Inadequate intakes of nutrients are associated with FNIH-defined sarcopenia in older men, but not with the other two sarcopenia definitions. Further studies are required to understand these relationships.
To examine changes in micronutrient intake over 3 years and identify any associations between socio-economic, health, lifestyle and meal-related factors and these changes in micronutrient intakes among older men.
Design:
Prospective study.
Setting:
Dietary adequacy of individual micronutrient was compared to the estimated average requirement of the nutrient reference values (NRV). Attainment of the NRV for twelve micronutrients was incorporated into a dichotomised variable ‘not meeting’ (meeting ≤ 6) or ‘meeting’ (meeting ≥ 7) and categorised into four categories to assess change in micronutrient intake over 3 years. The multinomial logistic regression analyses were conducted to model predictors of changes in micronutrient intake.
Participants:
Seven hundred and ninety-four men participated in a detailed diet history interview at the third wave (baseline nutrition) and 718 men participated at the fourth wave (3-year follow-up).
Results:
The mean age was 81 years (range 75–99 years). Median intakes of the majority of micronutrients decreased significantly over a 3-year follow-up. Inadequacy of the NRV for thiamine, dietary folate, Zn, Mg, Ca and I were significantly increased at a 3-year follow-up than baseline nutrition. The incidence of inadequate micronutrient intake was 21 % and remained inadequate micronutrient intake was 16·4 % at 3-year follow-up. Changes in micronutrient intakes were significantly associated with participants born in the UK and Italy, low levels of physical activity, having ≥2 medical conditions and used meal services.
Conclusions:
Micronutrient intake decreases with age in older men. Our results suggest that strategies to improve some of the suboptimal micronutrient intakes might need to be developed and implemented for older men.
Dopaminergic pathways are implicated in motivational aspects of substance use disorders, and might contribute to withdrawal phenomena, as well as an increased long-term risk of relapse. Molecular imaging with positron emission tomography (PET) revealed reductions in the availability of binding sites for D2/3receptor ligands in striatum of withdrawn abusers of cocaine; corresponding results in alcoholics have been inconsistent so far. In the present study, we used the D2/3ligand [18F]fallypride to investigate dynamic changes in receptor availability in the striatum of patients with alcohol use disorder before and after undergoing a detoxification protocol.
Methods
18 male patients (mean age 44±5.3y) with alcohol use disorder were recruited and scanned with 180MBq [18F]fallypride upon hospital admission, and again 1-2 weeks later after detoxification. The control group consisted of 10 age-matched healthy volunteers. PET acquisition time was 180min, consisting of 39 frames of increasing duration. Within each group binding potentials (BPND) were calculated in the striatum using the cerebellum as reference.
Results
In the patients, the mean BPND in whole striatum was 17.2±4.2 at baseline, with a trend towards a decline at follow-up. In addition there were inverse correlations of BPNDwith age (r-0.45) and with daily alcohol consumption (r-0.2). The age-dependence of BPNDwas less pronounced in healthy controls. However, mean striatal BPNDwas only slightly lower in the patient group. No pronounced group differences were evident for extrastriatal [18F]fallypride binding.
Conclusions
Regressions with age suggest an accelerated loss of dopamine D2/3 receptors in the striatum of subjects with alcohol use disorder.