A randomised controlled trial of an exercise intervention promoting activity, independence and stability in older adults with mild cognitive impairment and early dementia (PrAISED) – A Protocol

© 2019 The Author(s). Background: People with dementia progressively lose cognitive and functional abilities. Interventions promoting exercise and activity may slow decline. We developed a novel intervention to promote activity and independence and prevent falls in people with mild cognitive impairment (MCI) or early dementia. We successfully undertook a feasibility randomised controlled trial (RCT) to refine the intervention and research delivery. We are now delivering a multi-centred RCT to evaluate its clinical and cost-effectiveness. Methods: We will recruit 368 people with MCI or early dementia (Montreal Cognitive Assessment score 13-25) and a family member or carer from memory assessment clinics, other community health or social care venues or an online register (the National Institute for Health Research Join Dementia Research). Participants will be randomised to an individually tailored activity and exercise programme delivered using motivational theory to promote adherence and continued engagement, with up to 50 supervised sessions over one year, or a brief falls prevention assessment (control). The intervention will be delivered in participants' homes by trained physiotherapists, occupational therapists and therapy assistants. We will measure disabilities in activities of daily living, physical activity, balance, cognition, mood, quality of life, falls, carer strain and healthcare and social care use. We will use a mixed methods approach to conduct a process evaluation to assess staff training and delivery of the intervention, and to identify individual- and context-level mechanisms affecting intervention engagement and activity maintenance. We will undertake a health economic evaluation to determine if the intervention is cost-effective. Discussion: We describe the protocol for a multi-centre RCT that will evaluate the clinical and cost-effectiveness of a therapy programme designed to promote activity and independence amongst people living with dementia. Trial registration: ISRCTN, ISRCTN15320670. Registered on 4 September 2018

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Potential health risks due to in-car aerosol exposure across ten global cities

Car microenvironments significantly contribute to the daily pollution exposure of commuters, yet health and socioeconomic studies focused on in-car exposure are rare. This study aims to assess the relationship between air pollution levels and socioeconomic indicators (fuel prices, city-specific GDP, road density, the value of statistical life (VSL), health burden and economic losses resulting from exposure to fine particulate matter ≤2.5 µm; PM2.5) during car journeys in ten cities: Dhaka (Bangladesh); Chennai (India); Guangzhou (China); Medellín (Colombia); São Paulo (Brazil); Cairo (Egypt); Sulaymaniyah (Iraq); Addis Ababa (Ethiopia); Blantyre (Malawi); and Dar-es-Salaam (Tanzania). Data collected by portable laser particle counters were used to develop a proxy of car-user exposure profiles. Hotspots on all city routes displayed higher PM2.5 concentrations and disproportionately high inhaled doses. For instance, the time spent at the hotspots in Guangzhou and Addis Ababa was 26% and 28% of total trip time, but corresponded to 54% and 56%, respectively, of the total PM2.5 inhaled dose. With the exception of Guangzhou, all the cities showed a decrease in per cent length of hotspots with an increase in GDP and VSL. Exposure levels were independent of fuel prices in most cities. The largest health burden related to in-car PM2.5 exposure was estimated for Dar-es-Salam (81.6 ± 39.3 μg m−3), Blantyre (82.9 ± 44.0) and Dhaka (62.3 ± 32.0) with deaths per 100,000 of the car commuting population per year of 2.46 (2.28–2.63), 1.11 (0.97–1.26) and 1.10 (1.05–1.15), respectively. However, the modest health burden of 0.07 (0.06–0.08), 0.10 (0.09–0.12) and 0.02 (0.02–0.03) deaths per 100,000 of the car commuting population per year were estimated for Medellin (23 ± 13.7 μg m−3), São Paulo (25.6 ± 11.7) and Sulaymaniyah (22.4 ± 15.0), respectively. Lower GDP was found to be associated with higher economic losses due to health burdens caused by air pollution in most cities, indicating a socioeconomic discrepancy. This assessment of health and socioeconomic parameters associated with in-car PM2.5 exposure highlights the importance of implementing plausible solutions to make a positive impact on peoples’ lives in these cities

In-car particulate matter exposure across ten global cities

Cars are a commuting lifeline worldwide, despite contributing significantly to air pollution. This is the first global assessment on air pollution exposure in cars across ten cities: Dhaka (Bangladesh); Chennai (India); Guangzhou (China); Medellín (Colombia); São Paulo (Brazil); Cairo (Egypt); Sulaymaniyah (Iraq); Addis Ababa (Ethiopia); Blantyre (Malawi); and Dar-es-Salaam (Tanzania). Portable laser particle counters were used to develop a proxy of car-user exposure profiles and analyse the factors affecting particulate matter ≤2.5 μm (PM2.5; fine fraction) and ≤10 μm (PM2.5–10; coarse fraction). Measurements were carried out during morning, off- and evening-peak hours under windows-open and windows-closed (fan-on and recirculation) conditions on predefined routes. For all cities, PM2.5 and PM10 concentrations were highest during windows-open, followed by fan-on and recirculation. Compared with recirculation, PM2.5 and PM10 were higher by up to 589% (Blantyre) and 1020% (São Paulo), during windows-open and higher by up to 385% (São Paulo) and 390% (São Paulo) during fan-on, respectively. Coarse particles dominated the PM fraction during windows-open while fine particles dominated during fan-on and recirculation, indicating filter effectiveness in removing coarse particles and a need for filters that limit the ingress of fine particles. Spatial variation analysis during windows-open showed that pollution hotspots make up to a third of the total route-length. PM2.5 exposure for windows-open during off-peak hours was 91% and 40% less than morning and evening peak hours, respectively. Across cities, determinants of relatively high personal exposure doses included lower car speeds, temporally longer journeys, and higher in-car concentrations. It was also concluded that car-users in the least affluent cities experienced disproportionately higher in-car PM2.5 exposures. Cities were classified into three groups according to low, intermediate and high levels of PM exposure to car commuters, allowing to draw similarities and highlight best practices

In-kitchen aerosol exposure in twelve cities across the globe

Poor ventilation and polluting cooking fuels in low-income homes cause high exposure, yet relevant global studies are limited. We assessed exposure to in-kitchen particulate matter (PM2.5 and PM10) employing similar instrumentation in 60 low-income homes across 12 cities: Dhaka (Bangladesh); Chennai (India); Nanjing (China); Medellín (Colombia); São Paulo (Brazil); Cairo (Egypt); Sulaymaniyah (Iraq); Addis Ababa (Ethiopia); Akure (Nigeria); Blantyre (Malawi); Dar-es-Salaam (Tanzania) and Nairobi (Kenya). Exposure profiles of kitchen occupants showed that fuel, kitchen volume, cooking type and ventilation were the most prominent factors affecting in-kitchen exposure. Different cuisines resulted in varying cooking durations and disproportional exposures. Occupants in Dhaka, Nanjing, Dar-es-Salaam and Nairobi spent > 40% of their cooking time frying (the highest particle emitting cooking activity) compared with ∼ 68% of time spent boiling/stewing in Cairo, Sulaymaniyah and Akure. The highest average PM2.5 (PM10) concentrations were in Dhaka 185 ± 48 (220 ± 58) μg m−3 owing to small kitchen volume, extensive frying and prolonged cooking compared with the lowest in Medellín 10 ± 3 (14 ± 2) μg m−3. Dual ventilation (mechanical and natural) in Chennai, Cairo and Sulaymaniyah reduced average in-kitchen PM2.5 and PM10 by 2.3- and 1.8-times compared with natural ventilation (open doors) in Addis Ababa, Dar-es-Salam and Nairobi. Using charcoal during cooking (Addis Ababa, Blantyre and Nairobi) increased PM2.5 levels by 1.3- and 3.1-times compared with using natural gas (Nanjing, Medellin and Cairo) and LPG (Chennai, Sao Paulo and Sulaymaniyah), respectively. Smaller-volume kitchens (3; Dhaka and Nanjing) increased cooking exposure compared with their larger-volume counterparts (Medellin, Cairo and Sulaymaniyah). Potential exposure doses were highest for Asian, followed by African, Middle-eastern and South American homes. We recommend increased cooking exhaust extraction, cleaner fuels, awareness on improved cooking practices and minimising passive occupancy in kitchens to mitigate harmful cooking emissions