A web-based pesticide risk assessment tool for drinking water protection zones in Sweden.

To protect human health, wildlife and the aquatic environment, "safe uses" of pesticides are determined at the EU level while product authorization and terms of use are established at the national level. In Sweden, extra precaution is taken to protect drinking water, and permits are therefore required for pesticide use within abstraction zones. This paper presents MACRO-DB, a tool for assessing pesticide contamination risks of groundwater and surface water, used by authorities to support their decision-making for issuing such permits. MACRO-DB is a meta-model based on 583,200 simulations of the physically-based MACRO model used for assessing pesticide leaching risks at EU and national level. MACRO-DB is simple to use and runs on widely available input data. In a qualitative comparative assessment for two counties in Sweden, MACRO-DB outputs were in general agreement with groundwater monitoring data and matched or were more protective than the national risk assessment procedure for groundwater.

Herpes Simplex Viral Infection Doubles the Risk of Dementia in a Contemporary Cohort of Older Adults: A Prospective Study.

Background: Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer's disease (AD). Objective: We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to anti-herpesvirus treatment and potential APOE ɛ4 carriership interaction. Methods: This study was conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001-2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied. Results: Cumulative AD and all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE ɛ4 or anti-CMV IgG. Similar results were obtained for HSV-1. Conclusions: HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.

Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases.

BACKGROUND: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH. METHODS: Lumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer's disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number. RESULTS: Three proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91. CONCLUSIONS: The inflammatory cytokines MCP-1 and CCL4 are present at higher-and PD-L1 at lower-levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH.

Greenhouse production contributes to pesticide occurrences in Swedish streams.

Greenhouse and other covered cultivation systems have increased globally over the past several decades, leading to considerably improved product quality and productivity per land area unit. However, there is a paucity in information regarding the environmental impacts of covered production systems, especially regarding pesticides entering the surrounding environment. Aiming to address this knowledge gap, we collected grab samples downstream of greenhouses from seven Swedish streams every 14 days during a 12 month period. In three of the streams, samples were also taken upstream of the greenhouses and in four of the streams time-integrated samples were collected by TIMFIE samplers in the period between grab sampling occasions. The samples were analyzed for 28 substances (27 that were permitted for use in greenhouse production systems in Sweden and one degradation product to a permitted substance). Pesticide use journals were collected from the greenhouse producers for the 12 month period. The results were examined for indications of greenhouse contributions to detection frequencies, maximum and average concentrations, and potential ecotoxicicity in several ways: (1) comparing locations downstream of greenhouses with registered use of a substance with those without registered use, (2) comparing results from this study with those from the Swedish environmental monitoring program of pesticides in surface water from catchments with no greenhouses from the same period and region, (3) comparing concentration trends with registered pesticide application times in the greenhouses, and (4) comparing up- and downstream concentrations. The results strongly suggest that greenhouse applications do contribute to pesticide occurrences, maximum and median concentrations for most of the pesticides included in this study, and to potential toxicity to aquatic organisms for several of them, most notably imidacloprid, acetamiprid, carbendazim, and pirimicarb.

Identification of Pesticide Transformation Products in Surface Water Using Suspect Screening Combined with National Monitoring Data.

Pesticides are widespread anthropogenic chemicals and well-known environmental contaminants of concern. Much less is known about transformation products (TPs) of pesticides and their presence in the environment. We developed a novel suspect screening approach for not well-explored pesticides (n = 16) and pesticide TPs (n = 242) by integrating knowledge from national monitoring with high-resolution mass spectrometry data. Weekly time-integrated samples were collected in two Swedish agricultural streams using the novel Time-Integrating, MicroFlow, In-line Extraction (TIMFIE) sampler. The integration of national monitoring data in the screening approach increased the number of prioritized compounds approximately twofold (from 23 to 42). Ultimately, 11 pesticide TPs were confirmed by reference standards and 12 TPs were considered tentatively identified with varying levels of confidence. Semiquantification of the newly confirmed TPs indicated higher concentrations than their corresponding parent pesticides in some cases, which highlights concerns related to (unknown) pesticide TPs in the environment. Some TPs were present in the environment without co-occurrence of their corresponding parent compounds, indicating higher persistency or mobility of the identified TPs. This study showcased the benefits of integrating monitoring knowledge in this type of studies, with advantages for suspect screening performance and the possibility to increase relevance of future monitoring programs.

Different Inflammatory Signatures in Alzheimer's Disease and Frontotemporal Dementia Cerebrospinal Fluid.

BACKGROUND: Neuroinflammatory processes are common in neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), but current knowledge is limited as to whether cerebrospinal fluid (CSF) levels of neuroinflammatory proteins are altered in these diseases. OBJECTIVE: To identify and characterize neuroinflammatory signatures in CSF from patients with AD, mild cognitive impairment (MCI), and FTD. METHODS: We used proximity extension assay and ANOVA to measure and compare levels of 92 inflammatory proteins in CSF from 42 patients with AD, 29 with MCI due to AD (MCI/AD), 22 with stable MCI, 42 with FTD, and 49 control subjects, correcting for age, gender, collection unit, and multiple testing. RESULTS: Levels of matrix metalloproteinase-10 (MMP-10) were increased in AD, MCI/AD, and FTD compared with controls (AD: fold change [FC] = 1.32, 95% confidence interval [CI] 1.14-1.53, q = 0.018; MCI/AD: FC = 1.53, 95% CI 1.20-1.94, q = 0.045; and FTD: FC = 1.42, 95% CI 1.10-1.83, q = 0.020). MMP-10 and eleven additional proteins were increased in MCI/AD, compared with MCI (q < 0.05). In FTD, 36 proteins were decreased, while none was decreased in AD or MCI/AD, compared with controls (q < 0.05). CONCLUSION: In this cross-sectional multi-center study, we found distinct patterns of CSF inflammatory marker levels in FTD and in both early and established AD, suggesting differing neuroinflammatory processes in the two disorders.

Measurement error of the Mini-Mental State Examination among individuals with dementia that reside in nursing homes.

Few studies have investigated the measurement error of the Mini-Mental State Examination (MMSE) in the same unit of measurement, also known as absolute reliability. This measurement can help determine whether an observed score change for an individual is likely to represent true change. The aim of this study was to investigate the absolute reliability of the MMSE among individuals with dementia that reside in nursing homes. Among 88 participants, 19 (21.6%) were men, 35 (39.8%) had Alzheimer's disease, 35 (39.8%) had vascular dementia, and the mean age was 84.0 years (range 65-98). The participants were tested and retested with the MMSE within 1-6 days. Both tests were administered by the same assessor at the same time of day. The mean MMSE score was 13.7 (range 0-28). The absolute difference between MMSE scores varied from 0 to 6 points, and the differences did not correlate with the corresponding score means (p = 0.874). The smallest detectable change (SDC) between two measurements was 4.00. The SDC was independent of depression, impaired vision and hearing, delirium within the last week, dementia type and age. However, the SDC was 5.56 among men and 3.50 among women (p = 0.003). In conclusion, for individuals with dementia that reside in nursing homes, it seems like their MMSE score needs to change by four or more points between two measurements in order for their score change to be reliably higher than the measurement error.

Effects of Exercise on Cognitive Function in Older People with Dementia: A Randomized Controlled Trial.

BACKGROUND: Although physical exercise has been suggested to influence cognitive function, previous exercise studies show inconsistent results in people with dementia. OBJECTIVES: To investigate effects of exercise on cognitive function in people with dementia. METHOD: The Umeå Dementia and Exercise (UMDEX) study, a cluster-randomized controlled trial, was set in 16 nursing homes in Umeå, Sweden. One hundred-and-forty-one women and 45 men with dementia; mean age of 85 y and mean Mini-Mental State Examination (MMSE) score of 15, were randomized to a High-Intensity Functional Exercise program or a seated attention control activity. Blinded assessors measured global cognitive function using the MMSE and the Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog), and executive function using Verbal fluency (VF) at baseline and 4 months (directly after intervention completion), and MMSE and VF at 7 months. RESULTS: Linear mixed models showed no between-group effects in mean difference from baseline (95% confidence intervals, CI) at 4 months in MMSE (-0.27; 95% CI -1.4 to 0.87, p = 0.644), ADAS-Cog (-1.04, 95% CI -4 to 1.92, p = 0.491), or VF (-0.53, 95% CI -1.42 to 0.35, p = 0.241) or at 7 months in MMSE (-1.15, 95% CI -2.32 to 0.03, p = 0.056) or VF (-0.18, 95% CI -1.09 to 0.74, p = 0.707). CONCLUSION: A 4-month, high-intensity functional exercise program had no superior effects on global cognition or executive function in people with dementia living in nursing homes when compared with an attention control activity.

Psychotropic drug use and mortality in old people with dementia: investigating sex differences.

BACKGROUND: Psychotropic drugs are common among old people with dementia, and have been associated with increased mortality. Previous studies have not investigated sex differences in this risk. This study was conducted to analyse associations between the use of antipsychotics, antidepressants, and benzodiazepines and 2-year mortality in old people with dementia, and to investigate sex differences therein. METHODS: In total, 1037 participants (74% women; mean age, 89 years) with dementia were included from four cohort studies and followed for 2 years. Data were collected through home visits and medical records. Cox proportional hazard regression models were used to analyse associations between ongoing baseline drug use and mortality. Multiple possible confounders were evaluated and adjusted for. RESULTS: In fully adjusted models including data from the whole population, no association between baseline psychotropic drug use and increased 2-year mortality was seen. Significant sex differences were found in mortality associated with antidepressant use, which was protective in men, but not in women (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40-0.92 and HR 1.09, 95% CI 0.87-1.38, respectively). The interaction term for sex was significant in analyses of benzodiazepine use, with a higher mortality risk among men than among women. CONCLUSIONS: Among old people with dementia, ongoing psychotropic drug use at baseline was not associated with increased mortality in analyses adjusted for multiple confounders. Sex differences in mortality risk associated with antidepressant and benzodiazepine use were seen, highlighting the need for further investigation of the impact of sex.

Antidepressant use and mortality in very old people.

BACKGROUND: Antidepressant treatment may increase the risk of death. The association between antidepressants and mortality has been evaluated in community-dwelling older people, but not in representative samples of very old people, among whom dementia, multimorbidity, and disability are common. METHODS: Umeå 85+/GERDA study participants (n = 992) aged 85, 90, and ≥95 years were followed for up to five years. Cox proportional hazard regression models were used to analyze mortality risk associated with baseline antidepressant treatment, adjusted for potential confounders. RESULTS: Mean age was 89 years; 27% of participants had dementia, 20% had stroke histories, 29% had heart failure, and 16% used antidepressants. In age- and sex-adjusted analyses, antidepressant use was associated with a 76% increased mortality risk (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.41-2.19). Adding adjustment for Geriatric Depression Scale score, HR was 1.62 (95% CI, 1.29-2.03). The association was not significant when adjusting for additional confounding factors (HR = 1.08; 95% CI, 0.85-1.38). Interaction analyses in the fully adjusted model revealed a significant interaction between sex and antidepressant use (HR: 1.76; 95% CI, 1.05-2.94). Among male and female antidepressant users, the HRs for death were 0.76 (95% CI, 0.47-1.24) and 1.28 (95% CI, 0.97-1.70), respectively. CONCLUSION: Among very old people, baseline antidepressant treatment does not seem to be independently associated with increased mortality risk. However, the risk may be different in men and women. This difference and the potential risk of initial treatment require further investigation in future cohort studies of very old people.

Effects of a high-intensity functional exercise program on depressive symptoms among people with dementia in residential care: a randomized controlled trial.

OBJECTIVES: The aim of this study is to evaluate the effect of a high-intensity functional exercise program on depressive symptoms among older care facility residents with dementia. METHODS: Residents (n = 186) with a diagnosis of dementia, age ≥ 65 years, Mini-Mental State Examination score ≥ 10, and dependence in activities of daily living were included. Participants were randomized to a high-intensity functional exercise program or a non-exercise control activity conducted 45 min every other weekday for 4 months. The 15-item Geriatric Depression Scale (GDS) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were administered by blinded assessors at baseline, 4, and 7 months. RESULTS: No difference between the exercise and control activity was found in GDS or MADRS score at 4 or 7 months. Among participants with GDS scores ≥ 5, reductions in GDS score were observed in the exercise and control groups at 4 months (-1.58, P = 0.001 and -1.54, P = 0.004) and 7 months (-1.25, P = 0.01 and -1.45, P = 0.007). Among participants with MADRS scores ≥ 7, a reduction in MADRS score was observed at 4 months in the control group (-2.80, P = 0.009) and at 7 months in the exercise and control groups (-3.17, P = 0.003 and -3.34, P = 0.002). CONCLUSIONS: A 4-month high-intensity functional exercise program has no superior effect on depressive symptoms relative to a control activity among older people with dementia living in residential care facilities. Exercise and non-exercise group activities may reduce high levels of depressive symptoms.

Blood pressure, gait speed, and mortality in very old individuals: a population-based cohort study.

OBJECTIVES: Clinical trials and observational studies have produced contradictory results regarding the association of blood pressure (BP) and mortality in people aged 80 years or older. Gait speed at usual pace has been shown to moderate this association in a population of noninstitutionalized people aged 65 years or older. The aims of this study were to investigate the association of BP with all-cause mortality in a representative sample of people aged 85 years or older and to assess whether gait speed moderates this association. DESIGN, SETTING, AND PARTICIPANTS: A total of 806 participants in the population-based prospective Umeå 85+/GERDA study aged 85, 90, and 95 years or older. MEASUREMENTS: Gait speed at usual pace was measured over 2.4 m. The main outcome was hazard ratios (HRs) for all-cause mortality according to systolic and diastolic BP categories in the total sample and in faster-walking (≥0.5 m/s, n = 312) and slower-walking (<0.5 m/s, n = 433) subcohorts; the latter also included habitually nonwalking participants. Comprehensive adjustments were made for sociodemographic and clinical characteristics associated with death. RESULTS: Mean age and baseline systolic and diastolic BP were 89.6 ± 4.6 years, 146.8 ± 23.9 mm Hg, and 74.8 ± 11.1 mm Hg, respectively. Most (n = 561 [69%]) participants were women, 315 (39%) were care facility residents, and 566 (70%) were prescribed BP-lowering drugs. Within 5 years, 490 (61%) participants died. In the total sample and slower-walking subcohort, systolic BP appeared to be inversely associated with mortality, although not independent of adjustments. Among faster-walking participants, mortality risk after adjustment was more than 2 times higher in those with systolic BP of 140 to 149 mm Hg (HR = 2.25, 95% confidence interval [CI] = 1.03-4.94) and 165 mm Hg or higher (HR = 2.13, 95% CI = 1.01-4.49), compared with systolic BP of 126 to 139 mm Hg. Mortality risk was also independently higher in faster-walking participants with diastolic BP higher than 80 mm Hg, compared with diastolic BP of 75 to 80 mm Hg (HR = 1.76, 95% CI = 1.07-2.90). CONCLUSION: The gait speed threshold of 0.5 m/s may be clinically useful for the distinction of very old people with and without increased all-cause mortality risk due to elevated systolic and diastolic BP.

Functional capacity and dependency in transfer and dressing are associated with depressive symptoms in older people.

BACKGROUND: This study examined associations between depressive symptoms and functional capacity, overall dependency in personal activities of daily living (ADLs), and dependency in individual ADL tasks, respectively, in people with a high mean age, large range of functional capacity, and wide spectrum of dependency in ADLs. METHODS: Cross-sectional data from three studies were used. A total of 392 individuals living in community and residential care facilities were included. Mean age was 86.2 years, 72% were women, 75% were dependent in ADLs, 42% had depression, and 39% had dementia. Depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), functional capacity with the Berg Balance Scale (BBS), and ADLs with the Barthel ADL Index. Multiple linear regression analyses with comprehensive adjustments were performed between GDS-15 and BBS, GDS-15 and Barthel ADL Index, and GDS-15 and each individual ADL task, separately. RESULTS: GDS-15 score was associated with BBS score (unstandardized b =-0.03, P=0.008), but not with Barthel ADL Index score (unstandardized b =-0.07, P=0.068). No significant interaction effects of sex, dementia, or living conditions were found in these associations. Among individual ADL tasks, dependency in transfer (unstandardized b =-1.03, P=0.007) and dressing (unstandardized b =-0.70, P=0.035) were associated with depressive symptoms. CONCLUSION: Functional capacity seems to be independently associated with depressive symptoms in older people living in community and residential care facilities, whereas overall ADL performance may not be associated. Dependency in the individual ADL tasks of transfer and dressing appear to be independently associated with depressive symptoms and may be an important focus of future interdisciplinary multifactorial intervention studies.

Risk factors for incident dementia in the very old.

BACKGROUND: Several risk factors for dementia, Alzheimer's disease, and cognitive impairment have been established; however, knowledge about risk factors in the very old population (≥85 years) is limited. This study describes the association of several baseline factors with dementia in participants aged ≥85 years, and investigates factors associated with a higher risk of incident dementia over five years. METHODS: The participants in this population-based cohort study were aged 85, 90, and ≥95 years at baseline (2000-2002). Data were collected during home visits for interviews and testing, from a review of medical records, and/or interviewing the caregiver or next of kin. After five years 212 participants could be followed up concerning incident dementia. Multivariate logistic regression was used. RESULTS: At baseline, 100/353 (28%) of participants had a dementia diagnosis. Over five years, 71/212 (33.5%) participants developed dementia. Few participants with dementia at baseline remained alive after five years (12%). Depression at the baseline and follow-up time were associated with a higher risk of dementia, odds ratio (OR) (95% CI, p-value) 2.91 (1.37-6.16, 0.005) and 1.61 (1.26-2.05, <0.001) respectively. More social contact and a higher Mini-Mental State Examination score at baseline were associated with lower risk of incident dementia, OR (95% CI, p-value) 0.87 (0.78-0.97, 0.009) and 0.83 (0.74-0.93, 0.001) respectively. CONCLUSIONS: Prevalence and incidence of dementia are high in very old people and dementia appears to be a fatal disorder. Depression is associated with higher risk of incident dementia over five years whereas more frequent social contacts and a higher MMSE score are associated with lower risk.

Is a change in functional capacity or dependency in activities of daily living associated with a change in mental health among older people living in residential care facilities?

AIM: Functional capacity and dependency in activities of daily living (ADL) could be important mediators for an association between physical exercise and mental health. The aim of this study was to investigate whether a change in functional capacity or dependency in ADL is associated with a change in depressive symptoms and psychological well-being among older people living in residential care facilities, and whether dementia can be a moderating factor for this association. METHODS: A prospective cohort study was undertaken. Participants were 206 older people, dependent in ADL, living in residential care facilities, 115 (56%) of whom had diagnosed dementia. Multivariate linear regression, with comprehensive adjustment for potential confounders, was used to investigate associations between differences over 3 months in Berg Balance Scale (BBS) and Geriatric Depression Scale (GDS-15) scores, and in BBS and Philadelphia Geriatric Center Morale Scale (PGCMS) scores. Associations were also investigated between differences in Barthel ADL Index and GDS-15 scores, and in Barthel ADL Index and PGCMS scores. RESULTS: There were no significant associations between changes in scores over 3 months; the unstandardized ß for associations between BBS and GDS-15 was 0.026 (P=0.31), BBS and PGCMS 0.045 (P=0.14), Barthel ADL Index and GDS-15 0.123 (P=0.06), and Barthel ADL Index and PGCMS -0.013 (P=0.86). There were no interaction effects for dementia. CONCLUSION: A change in functional capacity or dependency in ADL does not appear to be associated with a change in depressive symptoms or psychological well-being among older people living in residential care facilities. These results may offer one possible explanation as to why studies of physical exercise to influence these aspects of mental health have not shown effects in this group of older people.