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•Air pollution may have deleterious effects on the central nervous system.•In aging, it is important to determine if air pollution exposure accelerates cognitive decline.•We studied ...exposure to three air pollutants: PM2.5, NO2 and black carbon.•Exposure to PM2.5 was associated with accelerated cognitive decline in our cohort.
Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with inconsistent results depending on the pollutant and the cognitive domain considered. We wanted to determine whether air pollution was associated with global and domain-specific cognitive decline.
This analysis used data from the French Three-City prospective cohort (participants aged 65 and older at recruitment and followed for up to 12 years). A battery of cognitive tests was administered at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test), semantic fluency (Isaacs Set Test) and executive functions (Trail Making Tests A and B). Exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) at the participants’ residential address during the 5 years before the baseline visit was estimated with land use regression models. Linear mixed models and latent process mixed models were used to assess the association of each pollutant with global and domain-specific cognitive decline.
The participants’ (n = 6380) median age was 73.4 years (IQR: 8.0), and 61.5% were women. At baseline, the median MMSE score was 28 (IQR: 3). Global cognition decline, assessed with the MMSE, was slightly accelerated among participants with higher PM2.5 exposure: one IQR increment in PM2.5 (1.5 µg/m3) was associated with accelerated decline (β: −0.0060 −0.0112; −0.0007 standard unit per year). Other associations were inconsistent in direction, and of small magnitude.
In this large population-based cohort, higher PM2.5 exposure was associated with accelerated global cognition decline. We did not detect any significant association for the specific cognitive domains or the other pollutants. Evidence concerning PM2.5 effects on cognition is growing, but more research is needed on other ambient air pollutants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim
Psychotropic drugs like opioids and benzodiazepines are prescribed for traumas resulting from road traffic crashes and the risk of developing an addiction deserves consideration. This study aims ...to shed light on how the consumption of those drugs evolves over time among older road traffic injury (RTI) victims.
Methods
We conducted a nationwide Swedish register‐based longitudinal study to identify trajectories of post‐RTI psychotropic drug use. All individuals aged 50 years and older who had a hospital visit for an RTI from 2007 to 2015 were followed up during a 2‐year period; those who used the drugs prior to the RTI were excluded. Trajectories were identified by performing latent class trajectory analysis on drug dispensation data for opioids and benzodiazepines separately (66 034 and 66 859 adults, respectively, in total).
Results
Three trajectories were identified for opioids and four for benzodiazepines. The largest group in both instances included people with no‐use/minimal use throughout the follow‐up (81.3% and 92.8%). “Sporadic users” were more frequent among users of opioids (16.7%) than benzodiazepines (4.3%), whereas “chronic users” were found in similar proportions (2.0% and 1.8%). “Delayed chronic use” characterized the fourth group of benzodiazepine users (1.0%).
Conclusion
Several trajectories of psychotropic drug use were identified after RTI, from limited to chronic. Although chronic use was uncommon, a better understanding of the factors likely to increase that risk is warranted given the seriousness of the problem.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive health, and this could be related to the effect of air pollution on ...vascular health. Objective: We aim to evaluate the association between air pollution exposure and a magnetic resonance imaging (MRI) marker of cerebral vascular burden, white matter hyperintensities (WMH). Methods: This cross-sectional analysis used data from the French Three-City Montpellier study. Randomly selected participants 65-80 years of age underwent an MRI examination to estimate their total and regional cerebral WMH volumes. Exposure to fine particulate matter (PM.sub.2.5), nitrogen dioxide (NO.sub.2), and black carbon (BC) at the participants' residential address during the 5 years before the MRI examination was estimated with land use regression models. Multinomial and binomial logistic regression assessed the associations between exposure to each of the three pollutants and categories of total and lobar WMH volumes. Results: Participants' (n = 582) median age at MRI was 70.7 years interquartile range (IQR): 6.1, and 52% (n = 300) were women. Median exposure to air pollution over the 5 years before MRI acquisition was 24.3 (IQR: 1.7) microg/m.sup.3 for PM.sub.2.5, 48.9 (14.6) microg/m.sup.3 for NO.sub.2, and 2.66 (0.60) 10.sup.-5/m for BC. We found no significant association between exposure to the three air pollutants and total WMH volume. We found that PM.sub.2.5 exposure was significantly associated with higher risk of temporal lobe WMH burden odds ratio (OR) for an IQR increase = 1.82 (95% confidence interval: 1.41, 2.36) for the second volume tercile, 2.04 (1.59, 2.61) for the third volume tercile, reference: first volume tercile. Associations for other regional WMH volumes were inconsistent. Conclusion: In this population-based study in older adults, PM.sub.2.5 exposure was associated with increased risk of high WMH volume in the temporal lobe, strengthening the evidence on PM.sub.2.5 adverse effect on the brain. Further studies looking at different markers of cerebrovascular damage are still needed to document the potential vascular effects of air pollution.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
When our brains are healthy, we can memorize, pay attention, reason, move, communicate, make decisions, and complete complex tasks. As some people get older, they can no longer do those things—they ...suffer from cognitive disorders that could indicate the start of dementia. Many factors might play a role in the development of dementia and some of those factors, like age and education level, have been identified. We know that there are additional, unidentified factors that play a role in the development of dementia, and scientists are discovering that where we live also matters. Our living environments include buildings and other structures, green spaces, and the level of air pollution. In this article, we explain the impact of the living environment on brain health decline during aging.
Introduction
No evidence exists about the impact of air pollution reduction on incidence of dementia. The aim of this study was to quantify how air quality improvement leads to dementia‐incidence ...benefits.
Methods
In the French Three‐City cohort (12 years of follow‐up), we used parametric g‐computation to quantify the expected number of prevented dementia cases under different hypothetical interventions with particulate matter measuring <2.5 μm (PM2.5) reductions.
Results
Among 7051 participants, 789 participants developed dementia. The median PM2.5 reduction between 1990 and 2000 was 12.2 (μg/m3). Such a reduction reduced the risk of all‐cause dementia (hazard ratio HR, 0.85; 95% confidence interval CI, 0.76 to 0.95). If all study participants were enjoying a hypothetical reduction of more than 13.10 μg/m3 (median reduction observed in the city of Montpellier), the rate difference was −0.37 (95% CI, −0.57 to −0.17) and the rate ratio was 0.67 (95% CI, 0.50 to 0.84).
Discussion
These findings highlight the possible substantial benefits of reducing air pollution in the prevention of dementia.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with ...inconsistent results depending on the pollutant and cognitive domain considered. We aimed to evaluate if air pollution was associated with global and domain‐specific cognitive decline.
Methods
We used data from the French Three‐City prospective cohort on 6380 participants aged 65 and older at recruitment and followed up for 12 years. Participants did cognitive tests at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test, BVRT), semantic fluency (Isaacs Set Test, IST) and executive functions (Trail Making Tests A and B, TMTA/B). Land‐use regression models were used to estimate fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) exposure at participants’ residential address over the 5‐year preceding the baseline visit. Linear mixed models were performed for each pollutant to evaluate their association with cognitive decline.
Results
Participants median age was 73.4 (IQR 8.0), and 61.5% were women. Baseline median scores were 28 (3) for MMSE, 12 (3) for BVRT, 48.0 (14.0) for IST, 0.5 (0.2) for TMTA, and 0.2 (0.2) for TMTB. We found a significantly worse decline in global cognition among participants with higher PM2.5 exposure: for PM2.5 levels ranging from 19.6 to 30.4 µg/m3, an IQR increment in PM2.5 (1.5) was associated with greater MMSE decline (β: 0.003 0.0006;0.006 per year). Other associations were inconsistent in direction and of small magnitude. For instance, an IQR increment in PM2.5 was associated with a 0.03 (‐0.002;0.060) change in IST decline and a ‐0.0003 (‐0.0009;0.0003) change in TMTA decline.
Conclusion
We found an adverse association between PM2.5 exposure and decline in global cognition. No significant associations were observed for the other pollutants and cognitive domains.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The immune control of hepatitis B virus (HBV) infection is essential for viral clearance. Therefore, restoring functional anti–HBV immunity is a promising immunotherapeutic approach to treatment of ...chronic infection. Plasmacytoid dendritic cells (pDCs) play a crucial role in triggering antiviral immunity through their ability to capture and process viral antigens and subsequently induce adaptive immune responses. We investigated the potential of pDCs to trigger antiviral cellular immunity against HBV. We used a human leukocyte antigen A (HLA–A)*0201+ pDC line loaded with HLA–A*0201‐restricted peptides derived from hepatitis B core/hepatitis B surface (HBc/HBs) antigens to amplify specific CD8 T cells ex vivo from chronic HBV patients and established a Hepato‐HuPBL mouse model to address the therapeutic potential of the strategy in vivo. Stimulation of PBMCs or liver‐infiltrating lymphocytes from HLA–A*0201+ chronic HBV patients by HBc peptide‐loaded pDCs elicited up to 23.1% and 76.1% HBV‐specific CD8 T cells in 45.8% of cases. The specific T cells from the “responder” group secreted interferon‐γ, expressed CD107 upon restimulation, and efficiently lysed HBV antigen‐expressing hepatocytes. Circulating hepatitis B e antigen (HBeAg) was found to distinguish the group of patients not responding to the pDC stimulation. The therapeutic efficacy of the pDC vaccine was evaluated in immunodeficient NOD‐SCID β2m−/− mice reconstituted with HBV patients' PBMCs and xenotransplanted with human HBV‐transfected hepatocytes. Vaccination of Hepato–HuPBL mice with the HBc/HBs peptide–loaded pDCs elicited HBV‐specific T cells able to specifically lyse the transfected hepatocytes and reduce the systemic viral load. Conclusion: pDCs loaded with HBV–derived peptides can elicit functional virus‐specific T cells. HBeAg appears to be critical in determining the outcome of immunotherapies in chronic HBV patients. A pDC‐based immunotherapeutic approach could be of interest in attempts to restore functional antiviral immunity, which is critical for the control of the virus in chronic HBV patients. (HEPATOLOGY 2012;56:1706–1718)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Predation shapes communities through consumptive and non‐consumptive effects. In the latter case, prey respond to perceived predation risk through proactive or reactive risk management strategies ...occurring at different spatial and temporal scales. The predator–prey space race and landscape of fear concepts are useful to better understand how predation risk affects prey behavioral decisions and distribution. We assessed predation risk effects in a terrestrial Arctic community, where the arctic fox is the main predator of ground‐nesting birds. Using high‐frequency GPS data, we estimated a predator activity landscape corresponding to fox space use patterns and validated with an artificial prey experiment that this predator activity landscape correlated with the predation risk landscape. We then investigated the effects of the fox activity landscape on multiple prey species, by assessing the anti‐predator behavior of a main prey (snow goose) actively searched for by foxes, and the nest distribution of several incidental prey species. We first found that snow geese showed a stronger level of nest defense in areas highly used by foxes, possibly responding with a reactive strategy to variation in predation risk. Then, nests of incidental prey reproducing in habitats easily accessed by foxes had a lower probability of occurrence in areas highly used by foxes, suggesting these birds may use a proactive risk management strategy by shifting their distribution away from risky areas. For incidental prey species nesting in microhabitat refuges difficult to access by foxes, probability of nest occurrence was independent of predation risk in the surrounding area, as they avoid risk at a finer spatial scale. By tracking all individuals of the dominant predator species in our study area, we demonstrated the value of using predator space use patterns to infer spatial variation in predation risk. Overall, we highlight the diversity of risk management strategies in prey sharing a common predator, hence refining our understanding of the mechanisms driving species distribution and community structure.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Consortium for the early identification of Alzheimer's disease–Quebec (CIMA-Q) created a research infrastructure to recruit, characterize, and track disease progression in individuals at risk of ...dementia.
CIMA-Q established standardized clinical, neuropsychological, neuroimaging, blood (plasma, serum, RNA, genomic DNA), cryopreserved peripheral blood mononuclear cells, and cerebrospinal fluid collection protocols. These data and biological materials are available to the research community.
In phase 1, 115 persons with subjective cognitive decline, 88 with mild cognitive impairment, 31 with early probable Alzheimer's disease, and 56 older adults with no worries nor impairments received detailed clinical and cognitive evaluations as well as blood and peripheral blood mononuclear cells collections. Among them, 142 underwent magnetic resonance imaging, 29 a 18fluorodeoxyglucose positron emission tomography, and 60 a lumbar puncture.
CIMA-Q provides procedures and resources to identify early biomarkers and novel therapeutic targets, and holds promise for detecting cognitive decline in Alzheimer's disease.
•Well-ascertained cohort of 290 community-dwelling elderly individuals in Quebec.•Large number of individuals with subjective cognitive decline studied longitudinally.•Clinical, neuropsychology, neuroimaging, and biomaterials available for Alzheimer's disease studies.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
Myotonic dystrophy type I (DM1) is one of the most frequent muscular dystrophies in adults. Although DM1 has long been considered mainly a muscle disorder, growing evidence suggests the ...involvement of peripheral nerves in the pathogenicity of DM1 raising the question of whether motoneurons (MNs) actively contribute to neuromuscular defects in DM1.
Methods
By using micropatterned 96‐well plates as a coculture platform, we generated a functional neuromuscular model combining DM1 and muscleblind protein (MBNL) knock‐out human‐induced pluripotent stem cells‐derived MNs and human healthy skeletal muscle cells.
Results
This approach led to the identification of presynaptic defects which affect the formation or stability of the neuromuscular junction at an early developmental stage. These neuropathological defects could be reproduced by the loss of RNA‐binding MBNL proteins, whose loss of function in vivo is associated with muscular defects associated with DM1. These experiments indicate that the functional defects associated with MNs can be directly attributed to MBNL family proteins. Comparative transcriptomic analyses also revealed specific neuronal‐related processes regulated by these proteins that are commonly misregulated in DM1.
Conclusions
Beyond the application to DM1, our approach to generating a robust and reliable human neuromuscular system should facilitate disease modelling studies and drug screening assays.
Myotonic dystrophy type 1 (DM1) is one of the most common hereditary muscular dystrophies in adult. In this study, we assessed the anterograde contribution of spinal motoneurons in the neuromuscular defects observed in DM1. By using micropatterned cocultures between human skeletal muscle cells and human‐induced pluripotent stem cells (hiPSC)‐spinal motoneurons derived from DM1 patients, our analysis revealed presynaptic defects including abnormal neuritogenesis, which affect the formation or stability of the neuromuscular junction. These defects can be reproduced by depleting muscleblind (MBNL) proteins whose loss‐of‐function is a key event in DM1 pathogenesis. Thus, our study highlighted the importance of considering the anterograde pathological contribution of spinal motoneurons in discovery future therapy for DM1.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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