Exercise interventions for older adults with Alzheimer's disease: a systematic review and meta-analysis protocol.

BACKGROUND: The growing societal and economic impact of Alzheimer's disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations. METHODS: This systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol. DISCUSSION: This review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175016 .

Aquatic hazard assessment of a commercial sample of naphthenic acids.

This paper presents chemical composition and aquatic toxicity characteristics of a commercial sample of naphthenic acids (NAs). Naphthenic acids are derived from the refining of petroleum middle distillates and can contribute to refinery effluent toxicity. NAs are also present in oil sands process-affected water (OSPW), but differences in the NAs compositions from these sources precludes using a common aquatic toxicity dataset to represent the aquatic hazards of NAs from both origins. Our chemical characterization of a commercial sample of NAs showed it to contain in order of abundance, 1-ring>2-ring>acyclic>3-ring acids (∼84%). Also present were monoaromatic acids (7%) and non-acids (9%, polyaromatic hydrocarbons and sulfur heterocyclic compounds). While the acyclic acids were only the third most abundant group, the five most abundant individual compounds were identified as C(10-14) n-acids (n-decanoic acid to n-tetradecanoic acid). Aquatic toxicity testing of fish (Pimephales promelas), invertebrate (Daphnia magna), algae (Pseudokirchneriella subcapitata), and bacteria (Vibrio fischeri) showed P. promelas to be the most sensitive species with 96-h LL50=9.0 mg L(-1) (LC50=5.6 mg L(-1)). Acute EL50 values for the other species ranged 24-46 mg L(-1) (EC50 values ranged 20-30 mg L(-1)). Biomimetic extraction via solid-phase-microextraction (BE-SPME) suggested a nonpolar narcosis mode of toxic action for D. magna, P. subcapitata, and V. fischeri. The BE analysis under-predicted fish toxicity, which indicates that a specific mode of action, besides narcosis, may be a factor for fishes.

Aquatic hazard and biodegradability of light and middle atmospheric distillate petroleum streams.

Light and middle atmospheric distillate petroleum substances are blended to produce fuels used in transportation and heating. These substances represent the majority by volume of crude oil refined products in the United States. The goal of this research was to develop biodegradability and aquatic toxicity data for four substances; heavy, straight-run naphtha (HSRN), hydro-desulfurized kerosene (HDK), hydro-cracked gas oil (HCGO), and catalytic-cracked gas oil (CCGO). Ready biodegradability tests demonstrated rapid and extensive microbial oxidation of these test substances, indicating a lack of persistence in the aquatic environment. Differences in biodegradation patterns reflected compositional differences in the constituent hydrocarbons. Results of aquatic toxicity tests on alga, cladocera, and fish demonstrated that toxicity was greatest for catalytic-cracked gas oil, which contained a high proportion of aromatic hydrocarbons. Aromatic hydrocarbons are more soluble, and hence more bioavailable, resulting in higher toxicity. When expressed on the basis of loading rates, acute toxicity values (LL/EL50) ranged between 0.3 and 5.5 mg L(-1) for all three species, while chronic no-observed-effect loading rates (NOELR) ranged between 0.05 and 0.64 mg L(-1). PETROTOX estimates for acute and chronic toxicity ranged from 0.18 to 2.3 mg L(-1) and 0.06 to 0.14 mg L(-1), respectively, which were generally more conservative than experimental data.

Assessment of the ecological effects of arsenic on a southern Ohio, USA stream.

Davis Creek is a southern Ohio, USA stream that receives a permitted discharge from the Belpre Elastomers Plant (BEP). A sediment quality triad investigation of Davis Creek was conducted over a 2-y period that included sediment and surface water chemistry measurements, toxicity tests of whole sediment, interstitial and surface water, and benthic and artificial substrate community assessments. The concentration of arsenic in surface and interstitial water was below United States Environmental Protection Agency ambient water quality criteria and was not toxic in laboratory tests (Ceriodaphnia dubia, Pimephales promelas). Similarly, sediments did not significantly affect survival and growth of Hyalella azteca and Chironomus tentans at most sampling locations despite sediments exceeding arsenic sediment screening values in nearly all samples collected. Differences in benthic community structure, determined by rapid bioassessment and Hester-Dendy sampling methods, were related primarily by variations in sediment moisture, particle size, and ammonia and not to arsenic concentrations. The Invertebrate Community Index (ICI) for Davis Creek was lower than values established for other warm-water ecoregional reference streams in Ohio. However, this ICI comparison may have been invalid because, unlike the reference streams, the Davis Creek watershed is small with intermittent headwater flow that limits macroinvertebrate recruitment and energy input. The sediment quality triad investigation indicated that Davis Creek was not significantly affected by arsenic associated with the BEP discharge despite having measured arsenic concentrations that exceeded sediment screening values.

A stream mesocosm study on the ecological effects of a C12-15 linear alcohol ethoxylate surfactant.

The responses of fish, invertebrates, and periphyton during a 56-day exposure to a C(12-15) linear alcohol ethoxylate surfactant were studied in stream mesocosms. An individual stream consisted of a slow-flowing pool section and a faster-flowing riffle section. The surfactant has an average distribution of nine ethoxylate groups per mole of alcohol. Eight stream mesocosms were used to test the effects of seven concentrations of the surfactant. Time-averaged, mean, measured concentrations were 20, 40, 70, 160, 300, 390, and 740 microg/L, which represented 70-100% of nominal concentrations. The exposure of aquatic communities to the C(12-15)AE-9 surfactant in stream mesocosms resulted in no-observed-effect concentrations (NOECs) for individual endpoints ranging from 160 to 740 microg/L. Among the more sensitive responses were Oncorhynchus mykiss time to swim up and fry growth, abundance of juvenile Gammarus pulex in drift samples, Baetis abundance in the riffle sediment and in samples collected from tiles placed in the riffle, and Simulium density in the riffle tiles, all with NOECs of 160 microg/L. Responses of the riffle sediment invertebrate assemblages assessed using multivariate methods support a NOEC of 160 microg/L. Abundances of G. pulex, Copepoda, and Agapetus sampled in the pools and pool tiles were not affected at the highest surfactant concentration tested after 56 days. Surfactant effects on periphyton and community leaf processing were seen at 300-390 microg/L. Based upon the responses of several taxa representing different trophic levels, a mesocosm NOEC of 160 microg/L can be stated for the C(12-15)AE-9 surfactant. This study provided additional data that can be used to reduce the uncertainty in extrapolating laboratory data to the field for the environmental risk assessment of alcohol ethoxylates.

Spatial and temporal variability in the structure of invertebrate assemblages in control stream mesocosms.

Outdoor stream mesocosm studies conducted between 1992 and 1996 at two facilities enabled the investigation of structural variability in invertebrate assemblages within and between studies. Temporal variability of benthic invertebrate assemblages between eight replicate streams within a study was assessed in a 28-day mesocosm study without chemical treatment. Cluster analysis, non-metric multidimensional scaling, and principal component analysis each showed the untreated assemblages as structurally distinct groups on the three sampling days. The assemblages between the eight replicate streams showed >88% Bray-Curtis similarity at any one time during the study. In addition, pre-treatment data from a series of four studies conducted at one facility were used to examine structural variability in the starting benthic invertebrate assemblages between studies. Invertebrate assemblages were structurally distinct at the start of each mesocosm study conducted in different years at the same facility and the taxa responsible for differences in the assemblages were also different each year. The implications of temporal and spatial variability in benthic invertebrate assemblages within and between mesocosm studies with regards to species sensitivity and study repeatability should be considered when results of such studies are used in risk assessment.

Multivariate analyses of invertebrate community responses to a C12-15 AE-3S anionic surfactant in stream mesocosms.

The ecological effects of a C(12-15)AE-3S linear alkylethoxysulfate anionic surfactant on aquatic organisms were studied in stream mesocosms. Analyses of the experimental data have yielded multiple population-level no-observed effect concentrations (NOECs) but did not provide a measure of community-level response to surfactant exposure. In the present study, the invertebrate data from the mesocosm study were further examined for community-level effects using multivariate techniques. Two multivariate statistical methods were selected as representative of recommended methods and used to analyze invertebrate abundance. One method was similarity analysis using the Bray-Curtis index, and the second method was the canonical ordination technique principal response curves recently developed for analysis of mesocosm data. Both sets of techniques detected statistically significant changes in invertebrate community structure following surfactant exposure. Ordinations constructed from Bray-Curtis similarity matrices provided clearer two-dimensional representations of these changes than ordinations from redundancy analysis. Re-displaying treatment and temporal effects on community structure on separate axes as response curves provided a clearer method for interpreting community response to surfactant exposure. Both approaches detected treatment effects in low and high abundance taxa. The highest rank abundance taxa in the pretreatment streams contributed very little to the differences observed between the control and treated streams. The same set of taxa was identified as the dominant drivers for structural differences between control and treated communities despite underlying mathematical differences in these two methods. Invertebrate community-level NOECs estimated from these different multivariate methods (2.5-5.0 mg/l) were comparable and these NOECs were similar to invertebrate population NOECs determined for this surfactant.

Ecological effects of an anionic C12-15 AE-3S alkylethoxysulfate surfactant in outdoor stream mesocosms.

The ecological assessment of a C12-15 AE-3S linear alkylethoxysulfate (AES) anionic surfactant to invertebrates, fish, periphyton, and an aquatic macrophyte was conducted in a 30-d outdoor stream mesocosm study with five replicated concentrations and controls. Alkylethoxysulfate structural integrity and exposure concentrations were maintained during the 30-d treatment period, with average measured concentrations of 0.7, 1.27, 2.2, 4.31, and 10.18 mg/L. No effects were observed on the aquatic macrophyte Myriophyllum aquaticum at the highest concentration tested. A sevenfold increase in periphyton biomass at 10.18 mg/L was observed relative to controls primarily because of increases in density of the filamentous alga Mougeotia sp. Densities of the invertebrates Annelida (Stylaria), Amphipoda, Copepoda, Trichoptera (Hydropsychidae), Cladocera, and Diptera (Chironomidae) significantly decreased in streams treated with AES at 10.18 mg/L. Densities of drifting invertebrates were not observed to be affected at any concentration tested. Reproduction of Pimephales promelas significantly decreased at 1.27 mg/L and growth of juvenile Lepomis macrochirus was significantly affected at 4.31 mg/L. Multivariate cluster analysis and nonmetric multidimensional scaling ordination showed distinct structural effects on the invertebrate communities in the streams treated with AES at 10.18 mg/ L compared to the control and streams treated at < 10.18 mg/L through the 30-d treatment. Convergence of the communities treated at 10.18 mg/L toward control communities in the ordination suggests recovery in these communities after termination of surfactant treatment. The results from this study support an ecosystem value of > 2.0 mg/L, and indicate that the conservative Dutch risk assessment for AESs has at least a fivefold margin of safety.

Toxicity of methyl tert-butyl ether to marine organisms: ambient water quality criteria calculation.

In response to increasing concerns over the detection of methyl tert-butyl ether (MTBE) in groundwater and surface water and its potential effects in aquatic ecosystems, industry and the United States Environmental Protection Agency (USEPA) began to collaborate in 1997 to develop aquatic toxicity databases sufficient to derive ambient water quality criteria for MTBE consistent with USEPA requirements. Acute toxicity data for seven marine species, chronic toxicity data for an invertebrate, and plant toxicity data were developed to complete the saltwater database. The species tested were Cyprinodon variegatus, Gasterosteus aculeatus, Callinectes sapidus, Mytilus galloprovincialis, Palaemonetes pugio, Rhepoxynius abronius, Americamysis bahia, and Skeletonema costatum. The toxicity tests were conducted in accordance with USEPA and American Society for Testing and Materials testing procedures and Good Laboratory Practice guidelines. Data developed from this study were consistent with existing data and showed that MTBE has low acute and chronic toxicity to the marine species tested. Based upon measured MTBE concentrations, acute effects were found to range from 166 mg MTBE/l for the grass shrimp to 1950 mg MTBE/l for marine mussel. The no-observed effect concentration for the reproduction and growth of mysids was 26 mg MTBE/l during the life cycle test. The toxicity of MTBE to saltwater organisms is comparable to its toxicity to the freshwater species tested. Reported MTBE concentrations in coastal waters are several orders of magnitude lower than concentrations observed to cause effects in marine organisms.