Greater Decline Research Articles

#5289 INTRARENAL RENIN-ANGIOTENSIN SYSTEM ACTIVATION ALTERS RELATIONSHIP BETWEEN SYSTOLIC BLOOD PRESSURE AND PROGRESSION OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Elevated blood pressure (BP) and intrarenal renin-angiotensin system (RAS) activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between BP and intrarenal RAS activity on the risk of CKD progression is unknown. Method We analyzed 2,076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic BP (SBP). The urinary angiotensinogen-to-creatinine (u-AGT/Cr) ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy. Results During 10,550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and u-AGT/Cr ratio on the risk of the primary outcome (P-for-interaction = 0.019). In patients with u-AGT/Cr <3.65 μg/gCr, the hazard ratios (HRs) (95% confidence intervals [CIs]) for SBP 120–129, 130–139, and ≥140 mmHg were 1.47 (1.08-2.01), 1.74 (1.26-2.39), and 2.43 (1.76-3.37), respectively, compared with SBP <120 mmHg. In addition, each 10 mmHg increase in SBP was associated with an 18% higher risk of CKD progression. Moreover, there was a greater decline in the estimated glomerular filtration rate among the higher SBP categories. However, these associations were not observed in patients with u-AGT/Cr ≥3.65 μg/gCr. Conclusion Urinary angiotensinogen levels may modify the association between SBP and adverse kidney outcomes.

#5699 IS GFR DECLINE INDUCED BY SGLT-2 INHIBITOR OF CLINICAL IMPORTANCE?

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcome and with nephroprotection independent of diabetes status. However, the use of SGLT2i often cause an initial decline in estimated glomerular filtration rate (eGFR). This study addresses the question whether there is a relationship between vascular improvement and GFR dipping. Method We measured GFR (mGFR) and calculated GFR (eGFR) in 65 patients with T2D at baseline and after 12 weeks of treatment with either a combination of Empagliflozin (E) + Linagliptin (L) (n = 34) or Metformin (M) + Insulin (I) (n = 31). mGFR was measured using the gold standard clearance technique by infusion of inulin. In addition, pulse wave velocity (PWV) was obtained at office and under ambulatory conditions. We splitted the study cohort according to the median change of mGFR after 12 weeks and compared the baseline characteristics. Results mGFR and eGFR decreased significantly with E+L and with M+I (Ott C et. al. Cardiovasc Diabetol. 2021). However, no correlation was noticed between the change of mGFR and change of eGFR for either treatment cohorts (E+L: p = 0.404; M+I: p = 0.460). We found a significant decrease in office PWV in the E+L group only (8.2±1.6 to 7.8±1.5, p = 0.028) without any change in 24-h PWV. The change of office PWV correlated with the change of mGFR (p = 0.009) in E+L group only and remained significant after adjustment for the change of office systolic BP (p = 0.018). In addition, we observed a correlation between the change of high sensitive C reactive protein (hsCRP) and change in mGFR (p = 0.031). We identified patients with higher albumin excretion (p = 0.044), higher fasting plasma glucose (p = 0.014) and high hsCRP (p = 0.057) to have a greater decline in mGFR with E+L. Conclusion First, eGFR may not be an appropriate parameter to assess the true change in renal function after receiving E+L in a single patient. Second, after E+L medication a high decrease in mGFR goes in parallel with vascular improvement and less inflammation thereby reflecting the pleiotropic pharmacologic effects of SGLT 2 inhibitors.

Quality of Life and Kidney Function in Older Adults: Prospective Data of the SCOPE Study.

A longitudinal alteration in health-related quality of life (HRQoL) over a two-year period and its association with early-stage chronic kidney disease (CKD) progression was investigated among 1748 older adults (>75 years). HRQoL was measured by the Euro-Quality of Life Visual Analog Scale (EQ-VAS) at baseline and at one and two years after recruitment. A full comprehensive geriatric assessment was performed, including sociodemographic and clinical characteristics, the Geriatric Depression Scale-Short Form (GDS-SF), Short Physical Performance Battery (SPPB), and estimated glomerular filtration rate (eGFR). The association between EQ-VAS decline and covariates was investigated by multivariable analyses. A total of 41% of the participants showed EQ-VAS decline, and 16.3% showed kidney function decline over the two-year follow-up period. Participants with EQ-VAS decline showed an increase in GDS-SF scores and a greater decline in SPPB scores. The logistic regression analyses showed no contribution of a decrease in kidney function on EQ-VAS decline in the early stages of CKD. However, older adults with a greater GDS-SF score were more likely to present EQ-VAS decline over time, whereas an increase in the SPPB scores was associated with less EQ-VAS decline. This finding should be considered in clinical practice and when HRQoL is used to evaluate health interventions among older adults.

Experimental assessment the effects of saline discharge on plankton community of the recipient freshwater ecosystem – Inputs to scientific ballast water management of inland ports

Expanding international trade has accelerated the transfer of ballast water worldwide, the change in salinity is expected to be detrimental to recipient areas’ species, especially to freshwater ports’. This study simulated the changes in freshwater plankton community with respect to salinity stress resulting from ballast water discharged. The prepared saline water (simulates ballast water that meets D-2 standards) was discharged into the collected freshwater samples (from natural lake) at different volume ratios, which represented the salinity changes in localized areas of the receiving waters. The samples were counted and identified for ≥ 10–50 µm and ≥ 50 µm organisms with FDA (Florescein Diacetate) & CMFDA (Chloromethylflurescein Diacetate) method and Microscope counting method. From the first day after saline water discharged, it was found that when water salinity reached 12.2 PSU (Practical salinity units), the density of ≥ 50 µm organism was about 0 ind./m3, while only when water salinity reached 24.8 PSU, the density of ≥ 10–50 µm organisms was 0 cells/mL from the sixth day after saline water discharged. When the salinity was less than or equal to 2.1 PSU, the composition of species of ≥ 50 µm organisms in samples were similar to the control group, but for ≥ 10–50 µm organisms, when the salinity was less than or equal to 6.5 PSU, the community structure in samples were similar to the control group. The ≥ 10–50 µm and ≥ 50 µm organisms, these two groups were differently responsive to the changes in salinity. Besides, when the change of water salinity doesn’t exceed 6.5 PSU, the density of plankton first decreased and then increased, but when salinity changes exceed 6.5 PSU, the density of plankton exhibited a great decline during ten days. The results indicated that high-salt ballast water discharge could negatively affect freshwater harbor organisms, the salinity indicators could provide the basis for future studies of actual water samples, pay attention to the impact of ballast water discharge on inland ports is urgent.

Associations of time in bed and sleep timing with dementia and cognitive decline among Chinese rural‐dwelling older adults: A cohort study

AbstractBackgroundThe longitudinal associations of time in bed (TIB) (a composite indicator of sleep duration, latency, and fragmentation) and sleep timing (a marker of circadian rhythms) with dementia and cognitive decline in older adults are unclear.MethodThis population‐based cohort study used data from 1982 participants in the Shandong Yanggu Study of Aging and Dementia, who were aged ≥60 years, free of dementia, and living in the rural communities in western Shandong Province, China. At the baseline (2014) and follow‐up (2018) examinations, sleep parameters were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Global cognitive function was measured using the Mini‐Mental State Examination (MMSE). Dementia was diagnosed following the DSM‐IV criteria, and the NIA‐AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional‐hazards models, and general linear models.ResultDuring the mean follow‐up of 3.7 (standard deviation = 0.3) years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J‐shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J‐shaped association with mid‐sleep time. When continuous sleep parameters were categorized into tertiles, the multivariable‐adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01‐2.83) for baseline sleep duration >8 hours (vs. 7‐8 hours), 2.17 (1.22‐3.87) for bedtime before 9PM (vs. 10PM or later), and 2.00 (1.23‐3.24) for mid‐sleep time before 1AM (vs. 1‐1.5AM). Early bedtime and mid‐sleep time were significantly associated with incident AD (multivariable‐adjusted HR range: 2.25‐2.51; P<0.05). Among individuals who were free of dementia at follow‐up, baseline long TIB, early bedtime and mid‐sleep time, early and late rise time, and prolonged TIB and advanced mid‐sleep time from baseline to follow‐up were associated with greater decline in MMSE score (P<0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged <75 years.ConclusionLong TIB and early sleep timing are associated with an increased risk of dementia and AD, and their associations with greater cognitive decline are evident only among young‐old people and men.

Differences in rate of change of retinal structural and microvasculature parameters in parkinson’s disease compared to controls

AbstractBackgroundPrior cross‐sectional studies have revealed decreased macular perfusion density (PFD) and increased peripapillary PFD in Parkinson’s disease (PD). We assess longitudinal rate of change of retinal microvascular and structural parameters in PD vs controls with normal cognition.MethodSubjects were imaged using Zeiss Cirrus HD‐5000 AngioPlex. Those with confounding medical or ocular comorbidities were excluded. Superficial capillary plexus (SCP) PFD and vessel density (VD) were assessed within ETDRS 6×6 circle, inner ring, outer ring and 3×3 circle and inner ring. SCP foveal avascular zone (FAZ) area was assessed. PFD, VD, FAZ, peripapillary retinal nerve fiber layer (RNFL), ganglion cell‐inner plexiform layer (GCIPL), and central subfield thickness (CST) were measured at 2 time points 1 year apart. Rate of change per year was calculated. Generalized estimating equations analyzed associations between rate of change of imaging parameters and PD.Result74 eyes of 40 patients with PD (60% male, mean age 67.47.9 years) & 149 eyes of 78 controls (28% male, mean age 70.35.8 years) were included. No demographic differences were observed between groups except higher proportion of females in controls (p = 0.001). PD had a greater decline in PFD in 6×6 circle (mean change per year = 0.021, control = 0.00, p = 0.001), 6×6 inner ring (PD = 0.018, control = 0.001, p = .007), 6×6 outer ring (PD = 0.022, control = 0.00, p = 0.001), 3×3 circle (PD = 0.016, control = 0.002, p<.001), 3×3 inner ring (PD = 0.016, control = 0.002, p<0.001). PD had greater decline in VD in 6×6 circle (mean change per year in PD = 0.72/mm, control = 0.054/mm, p = 0.006), 6×6 inner ring (PD = 0.636/mm, control = 0.048/mm, p = 0.03), 6×6 outer ring (PD = 0.746/mm, control = 0.054/mm, p = 0.005), 3×3 circle (PD = 0.939/mm, control = 0.006/mm, p<0.001), 3×3 inner ring (PD = ‐0.942/mm, control = 0.013/mm, p<0.001). PD had greater decrease in GCIPL (mean change per year in PD = 0.403µm, control = 0.128µm control, p = 0.01). There were no significant differences in rate of change in FAZ area, RNFL thickness, CST, and no significant differences in rate of change when stratified by PD severity.ConclusionPD may be associated with more rapid loss of retinal microvascular perfusion and vessel densities and more rapid thinning of GCIPL compared to normal aging in controls with normal cognition.

Trends and survival of malignant mesothelioma across racial groups between 2000-2019: A real-world study.

e20539 Background: Malignant mesothelioma of the pleura (MMP) is a rare and aggressive malignancy and predominantly affects patients of White race in the U.S. Despite treatment advancements, the 5-year survival rate remains between 5% and 10%. Studies assessing racial disparities in MMP are lacking. We conducted a retrospective study to evaluate prevalence, survival and mortality trends among racial groups. Methods: We used the SEER database to determine the racial prevalence of all histological subtypes of MMP between 2000 and 2019. We calculated racial and histological subtype survival Cox proportional hazard ratios while controlling for age, gender, ethnicity, surgery, chemotherapy, and radiation use. Second, we used the CDC WONDER database to identify all mesothelioma deaths for the same period. Age-adjusted mortality (AAM) rates per 100,000 persons were standardized to 2000 US census data and stratified by race. Results: A total of 12791 patients were identified, mostly White (95%), followed by Blacks (%5) and Asians (0.4%). The percentages of patients with epithelioid, sarcomatoid and biphasic histologies were as follows: Whites (67.6%, 19.2%, 13.2%), Blacks (70.4%, 19.4%, 10.1%), and Asians (64.4%, 23.6%, 11.9%). As demonstrated in Table 1, compared to Whites, regardless of stage, survival was worse for Blacks (HR 1.16) and Asians (HR 1.14). As expected, survival was inferior for pts with sarcomatoid MMP followed by biphasic. Epithelioid MMP had the most favorable prognosis. Lastly, using the CDC WONDER database over the same period, there were 47,323 White, 2,068 Black, and 541 Asian MMP deaths. AAM was 0.8, 0.3, and 0.2 per 100,000 persons for White, Black, and Asian patients, respectively. AAM declined from 2000 to 2019 by 22% (0.9 to 0.7) in White, 50% (0.4 to 0.2) in Black, and 33% (0.3 to 0.2) in Asian. Conclusions: This is one of the largest population-based studies analyzing MMP racial disparities and histologic subtypes. Mortality analysis revealed declines across all racial groups, with the greatest decline among Blacks, which is two-fold that of Whites. However, a survival gap between races and histological subtypes persists. Despite no differences in the prevalence of histologic subtypes, mortality was 16% higher for Black patients when compared to Whites. Asian patients also had a higher risk of death of 14%, though the aggressive sarcomatoid subtype was more prevalent in this racial group. Social determinants of health and biological differences, could be responsible. Further studies are needed. [Table: see text]

Updated APOE and TOMM40 rs2075650 genotype effects on cognition: a UK Biobank study

AbstractBackground58‐79% of late‐onset Alzheimer’s disease (AD) is due to genetic heritability. The epsilon 4 (ε4) variant of Apolipoprotein E (APOE) is the strongest genetic risk factor for AD, yet only accounts for 20% of AD heritability. In addition, the APOE ε2 or ε3 variants appear to have either a protective or neutral effect on AD risk respectively. Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is next to APOE and may modulate different APOE variant effects, such as with the Single Nucleotide Polymorphism (SNP) at rs2075650. Thus, we explored main and interaction effects of TOMM40 and APOE on longitudinal measures of executive function and memory.Method10,347 adults (40‐70y) in the UK Biobank were genotyped for APOE and TOMM40 ‘650. Executive function and memory were tested at baseline and twice over a period of 6‐10 years. Main effects within APOE haplotypes and TOMM40 SNP genotypes (A,G) were analyzed, as well as interactions between these genetic markers.ResultHaving the TOMM40 ‘650 G risk variant was related to better baseline cognitive scores regardless of APOE haplotype (ps <.05), but a greater decline over time in APOE4 carriers (ps <.05) The effects of the APOE haplotype were strongly modulated by sex. Men vs. women had less protective or more detrimental effects based on APOE2 or APOE4 haplotype respectively.ConclusionThe data suggests that TOMM40 modulates APOE, regardless of its haplotype. Future studies should stratify APOE by haplotype to re‐test our findings. In addition, more research needs to be done on the effect of having what we term a “mixed” APOE haplotype (carrying a copy of both the protective and risk gene variants).

Longitudinal association of edentulism with cognitive impairment, sarcopenia and all-cause mortality among older Chinese adults

BackgroundTooth loss may be a surrogate for systemic health and aging. However, no previous studies have systematically assessed multiple outcomes relevant to aging trajectory in this area, and many important confounders were not adjusted in most previous studies. This study aims to prospectively evaluate the associations of complete tooth loss (edentulism) with broad markers of sarcopenia, cognitive impairment and mortality.MethodsData were derived from the China Health and Retirement Longitudinal Study, a nationally representative household study of the Chinese population aged 45 years and older. Multivariate Weibull proportional hazards regression was used to assess the association between edentulism with sarcopenia and all-cause mortality. Average changes in cognitive function by edentulism was estimated by mixed-effects linear regression models.ResultsDuring the 5-year follow-up, the prevalence of edentulism among adults aged 45 and over was 15.4%. Participants with edentulism had a greater decline in cognitive function compared to those without (β=-0.70, 95%CI:-1.09, -0.31, P < 0.001). The association of edentulism and all-cause mortality for 45–64 age group (HR = 7.50, 95%CI: 1.99, 28.23, P = 0.003), but not statistically significant for the ≥ 65 age group (HR = 2.37, 95%CI: 0.97, 5.80, P = 0.057). Effects of edentulism on sarcopenia are statistically significant for all age groups (45–64 age group: HR = 2.15, 95%CI: 1.27, 3.66, P = 0.005; ≥65 age group: HR = 2.15, 95%CI: 1.27, 3.66, P = 0.002).ConclusionsThese findings could have important clinical and public health implications, as tooth loss is a quick and reproducible measurement that could be used in clinical practice for identifying persons at risk of accelerated aging and shortened longevity, and who may benefit most from intervention if causality is established.

Sex differences in outcomes of people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor

BackgroundThere is a well described sex-disparity in outcomes of individuals with cystic fibrosis (CF), with females faring worse than males. Given the dramatic improvement in overall health of people with CF using CF transmembrane conductance regulator (CFTR) modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), the sex-disparity in CF warrants re-examination. MethodsWe evaluated the effects of ETI use by sex prior to versus after initiation of ETI by pulmonary exacerbations (PEx), percent predicted forced expiratory volume in one second (ppFEV1), presence of Pseudomonas aeruginosa in sputum cultures, and body mass index (BMI). We used univariate and multivariable longitudinal regression adjusting for key confounders, such as age, race, CFTR modulator taken prior to ETI and baseline ppFEV1. ResultsWe included 251 individuals started on ETI between January 2014 to September 2022. We collected data for a mean of 5.45 years pre-ETI and 2.38 years post-ETI. We found the adjusted presence of PEx decreased more in males than females pre- to post-ETI with the odds of having a PEx in males being 0.57 (43% reduction) versus females 0.75 (25% reduction) (p = 0.049). We found no statistical difference by sex for ppFEV1, presence of Pseudomonas aeruginosa or BMI pre- to post-ETI by sex. ConclusionAfter treatment with ETI, there was a greater decline in PEx in males versus females. Long-term impact of ETI by sex is still unknown, but we will need to seek ways to effectively tailor care for individuals with CF and consider pharmacokinetic studies of ETI comparing males to females.

Gender differences in cardiovascular health over adolescence using the novel Life's Essential 8 score

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): 1. Fondo de Investigación Sanitaria - Instituto de Salud Carlos III 2. SHE Foundation and “la Caixa” Foundation. Background/Introduction The evidence for gender differences in overall cardiovascular health (CVH) score and individual health metrics over adolescence is conflicting. Purpose To study gender differences in overall CVH status and its individual metrics in a large cohort of adolescents aged 12 to 16 years in Spain. Methods This study collected longitudinal data from 1324 adolescents at baseline (48.4% girls; 12.5 (0.4) years), 1211 (47.9% girls; 13.9 (0.4) years) at first follow-up and 1095 at second follow-up (48.2% girls; 15.8 (0.4) years) attending 24 secondary schools enrolled in the SI! Program for Secondary Schools trial in Spain. Eight individual metrics (nicotine exposure, diet, physical activity (PA), sleep health, body mass index (BMI), blood glucose, non-high-density lipoprotein cholesterol, and blood pressure (BP)) were measured and scored from 0 to 100 points according to the Life’s Essential 8 (LE8) criteria established by the American Heart Association. An overall CVH score was constructed summing the metrics described above, ranging from 0 to 100 points. Low, moderate, or high overall CVH score was defined as 0-49, 50-79, or 80-100 points, respectively. Differences in CVH over time were analyzed in individuals with CVH score available at three time-points (n=1077) using generalized linear mixed adjusted models. Results At approximately 12 years of age, most individuals had a moderate or high LE8 CVH score and CVH was slightly higher (healthier) in girls than boys (77.2 vs. 76.0 points) (Figure 1). LE8 CVH score increased significantly in boys and girls between 12 and 14 years of age (1.78 and 1.95 points, respectively), without gender differences (Figure 2). LE8 CVH score decreased significantly in boys and girls between 14 and 16 years of age; however, this decline was higher in boys than in girls (-3.17 versus -1.62 points, p value=0.007). Regarding individual metrics, mean scores were lowest for the diet, and sleep health and highest for BP. The highest declines over time were observed in PA, especially in boys, and nicotine exposure, especially in girls. Conclusions Most adolescents had a moderate or high overall CVH status, although boys showed slightly unhealthier scores and greater decline over time. Gender differences in individual CVH metrics were also found. This information is helpful for tailoring health promotion programs in adolescence.

Longitudinal changes in Alzheimer's-related plasma biomarkers and brain amyloid.

Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer's progression assessment strategies. We examined the temporal order of changes in plasma amyloid-β ratio ( ), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios ( , ) relative to 11 C-Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB-/+). Participants (n=199) were cognitively normal at index visit with a median 6.1-year follow-up. PiB groups exhibited different rates of longitudinal change in . Change in brain amyloid correlated with change in GFAP (r=0.5, 95% CI=[0.26, 0.68]). The greatest relative decline in (-1%/year) preceded brain amyloid positivity by 41 years (95% CI=[32, 53]). Plasma may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time. HIGHLIGHTS Plasma declines over time among PiB- but does not change among PiB+. Phosphorylated-tau to Aβ42 ratios increase over time among PiB+ but do not change among PiB-. Rate of change in brain amyloid is correlated with change in GFAP and neurofilament light chain. The greatest decline in may precede brain amyloid positivity by decades.

Language dysfunction correlates with cognitive impairments in older adults without dementia mediated by amyloid pathology.

Previous studies have explored the application of non-invasive biomarkers of language dysfunction for the early detection of Alzheimer's disease (AD). However, language dysfunction over time may be quite heterogeneous within different diagnostic groups. Patient demographics and clinical data were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for the participants without dementia who had measures of cerebrospinal fluid (CSF) biomarkers and language dysfunction. We analyzed the effect of longitudinal neuropathological and clinical correlates in the pathological process of semantic fluency and confrontation naming. The mediation effects of AD biomarkers were also explored by the mediation analysis. There were 272 subjects without dementia included in this analysis. Higher rates of decline in semantic fluency and confrontation naming were associated with a higher risk of progression to MCI or AD, and a greater decline in cognitive abilities. Moreover, the rate of change in semantic fluency was significantly associated with Aβ deposition, while confrontation naming was significantly associated with both amyloidosis and tau burden. Mediation analyses revealed that both confrontation naming and semantic fluency were partially mediated by the Aβ aggregation. In conclusion, the changes in language dysfunction may partly stem from the Aβ deposition, while confrontation naming can also partly originate from the increase in tau burden. Therefore, this study sheds light on how language dysfunction is partly constitutive of mild cognitive impairment and dementia and therefore is an important clinical predictor.

Combinatory effects of microplastics and emerging contaminants on alga Chlamydomonas reinhardtii

In oceans today, there is much concern about the effects of microplastics (MPs) and other emerging contaminants (ECs). Here, the authors investigated the combinatory effects of the MPs poly(vinyl chloride) (PVC) and acrylates/C10–30 alkyl acrylates cross-polymer (AC) (which are commonly found in face wash), together with 2-phenoxyethanol (an EC commonly used in soaps). The model photosynthetic unicellular alga Chlamydomonas reinhardtii was used to study the potential of these pollutants to initiate algal blooms. It was shown that AC alone resulted in a greater decline in algal biomass as compared with PVC in the short term (14 days). While algal cultures exposed to PVC registered the highest increase in concentrations of the chlorophyll a pigment, it was the combinatory effects of each MP and 2-phenoxyethanol that were the most pronounced in terms of the large increase in algal biomass and the formation of extracellular polymeric substances. Proliferative growths of C. reinhardtii after prolonged exposure to AC–EC contaminants show potential for initiating algal blooms in aquatic environments. Hence, AC should be considered for regulation of waste water removal into water bodies, and other combinations of MPs and ECs should also be investigated.

Ten-Year Trends in Psychotropic Prescribing and Polypharmacy in Australian General Practice Patients with and without Dementia.

Little research has evaluated trends in psychotropic prescribing and polypharmacy in primary care patients, especially those with dementia. We sought to examine this in Australia from 2011 to 2020 using the primary care dataset, MedicineInsight. Ten consecutive serial cross-sectional analyses were performed to evaluate the proportion of patients aged 65 years or more, with a recorded diagnosis of dementia, who were prescribed psychotropic medications within the first six months of each year from 2011 to 2020. This proportion was compared with propensity score-matched control patients without dementia. Before matching, 24,701 patients (59.2% females) with, and 72,105 patients (59.2% females) without, a recorded diagnosis of dementia were included. In 2011, 42% (95% confidence interval [CI] 40.5-43.5%) of patients in the dementia group had at least one recorded prescription of a psychotropic medication, which declined to 34.2% (95% CI 33.3-35.1%; p for trend < 0.001) by 2020. However, it remained unchanged for matched controls (36% [95% CI 34.6-37.5%] in 2011 and 36.7% [95% CI 35.7-37.6%] in 2020). The greatest decline in the dementia groups by medication class was for antipsychotics (from 15.9% [95% CI 14.8-17.0%] to 8.8% [95% CI 8.2-9.4%]; p for trend < 0.001). During this period, the prevalence of psychotropic polypharmacy (use of two or more individual psychotropics) also decreased from 21.7% (95% CI 20.5-22.9%) to 18.1% (95% CI 17.4-18.9%) in the dementia groups, and slightly increased from 15.2% (95% CI 14.1-16.3%) to 16.6% (95% CI 15.9-17.3%) in the matched controls. The decline in psychotropic prescribing, particularly antipsychotics, in Australian primary care patients with dementia is encouraging. However, psychotropic polypharmacy still occurred in almost one in five patients with dementia at the end of the study period. Programs focused on encouraging further reductions in the use of multiple psychotropic drugs in patients with dementia are recommended, particularly in rural and remote regions.

Baseline Differences in Driving Frequency as a Predictor of Cognitive Decline and Alzheimer's Disease.

To extend prior research by examining daily driving frequency as a predictor of cognitive decline and later diagnosis of Alzheimer's disease. 1,426 older adults completed batteries of questionnaires and neuropsychological tests at baseline and yearly follow-ups (M = 6.8, SD = 4.9). Linear mixed effects models were estimated to examine whether daily driving frequency at baseline was predictive of cognitive decline while accounting for IADLs, mobility, depression, and demographics. Cox regression was used to examine driving frequency as a predictor of Alzheimer's disease diagnosis. Less daily driving frequency was associated with greater decline in all cognitive domains over time except for working memory. Although driving frequency was associated with these changes in cognition, it did not uniquely predict the development of Alzheimer's disease when accounting for other factors (eg, other IADLs). Our findings extend prior research linking driving cessation to greater levels of cognitive decline. Future work might benefit from examining the utility of driving habits (especially changes in driving) as measures of everyday functioning in older adult evaluations.

The association of low birthweight and prematurity on outcomes in children and adults with nephrotic syndrome-a NEPTUNE cohort study.

In single-center studies, both preterm birth and low birth weight (LBW) are associated with worse outcomes in childhood nephrotic syndrome. Using the Nephrotic Syndrome Study Network (NEPTUNE) observational cohort, we tested the hypothesis that in patients with nephrotic syndrome, hypertension, proteinuria status, and disease progression would be more prevalent and more severe in subjects with LBW and prematurity singly or in combination (LBW/prematurity). Three hundred fifty-nine adults and children with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) and available birth history were included. Estimated glomerular filtration rate (eGFR) decline and remission status were primary outcomes, and secondary outcomes were kidney histopathology, kidney gene expression, and urinary biomarkers. Logistic regression was used to identify associations with LBW/prematurity and these outcomes. We did not find an association between LBW/prematurity and remission of proteinuria. However, LBW/prematurity was associated with greater decline in eGFR. This decline in eGFR was partially explained by the association of LBW/prematurity with APOL1 high-risk alleles, but the association remained after adjustment. There were no differences in kidney histopathology or gene expression in the LBW/prematurity group compared to normal birth weight/term birth. LBW and premature babies who develop nephrotic syndrome have a more rapid decline in kidney function. We did not identify clinical or laboratory features that distinguished the groups. Additional studies in larger groups are needed to fully ascertain the effects of (LBW) and prematurity alone or in combination on kidney function in the setting of nephrotic syndrome.

Depression and Loneliness among the Elderly in Low- and Middle-Income Countries

We combine data from longitudinal surveys in seven low- and middle-income countries (plus the United States for comparison) to document that depressive symptoms among those aged 55 and above are prevalent in those countries and, unlike in the United States, increase sharply with age. Depressive symptoms in one survey wave are associated with a greater decline in ability to carry out basic daily activities and a higher probability of death in the next wave. Using additional data from a panel survey we conducted in Tamil Nadu with a focus on elderly living alone, we document that social isolation, poverty, and physical health challenges are strongly correlated with depression. We discuss potential policy interventions in these three domains, including some results from our randomized control trials in the Tamil Nadu sample.

Impact of cardiac surgery associated acute kidney injury on 1-year major adverse kidney events.

The incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30%, and the risk of chronic kidney disease (CKD) has been found to be higher in these patients compared to the AKI-free population. The aim of our study was to assess the risk of major adverse kidney events (MAKE) [25% or greater decline in estimated glomerular filtration rate (eGFR), new hemodialysis, and death] after cardiac surgery in a Spanish cohort and to evaluate the utility of the score developed by Legouis D etal. (CSA-CKD score) in predicting the occurrence of MAKE. This was a single-center retrospective study of patients who required cardiac surgery with cardiopulmonary bypass (CPB) during 2015, with a 1-year follow-up after the intervention. The inclusion criteria were patients over 18 years old who had undergone cardiac surgery [i.e., valve substitution (VS), coronary artery bypass graft (CABG), or a combination of both procedures]. The number of patients with CKD (eGFR <60 mL/min) increased from 74 (18.3%) to 97 (24%) within 1 year after surgery. The median eGFR declined from 85 to 82 mL/min in the non-CSA-AKI patient group and from 73 to 65 mL/min in those with CSA-AKI (p=0.024). Fifty-eight patients (1.4%) presented with MAKE at the 1-year follow-up. Multivariate logistic regression analysis showed that the only variable associated with MAKE was CSA-AKI [odds ratio (OR) 2.386 (1.31-4.35), p=0.004]. The median CSA-CKD score was higher in the MAKE cohort [3 (2-4) vs. 2 (1-3), p < 0.001], but discrimination was poor, with a receiver operating characteristic curve (AUC) value of 0.682 (0.611-0.754). Any-stage CSA-AKI is associated with a risk of MAKE after 1 year. Further research into new measures that identify at-risk patients is needed so that appropriate patient follow-up can be carried out.

Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women.

Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ 4 (APOE ℇ 4) genotype. Grip strength and TUG were assessed in community-dwelling older women (mean±SD; age 75.0±2.6years) at baseline (n=1225) and 5years (n=1052). Incident 14.5-year late-life dementia events (dementia-related hospitalization/death) were obtained from linked health records. Cardiovascular risk factors (Framingham Risk Score), APOE genotyping, prevalent atherosclerotic vascular disease and cardiovascular-related medications were evaluated at baseline. These were included in multivariable-adjusted Cox-proportional hazards models assessing the relationship between muscle function measures and late-life-dementia events. Over follow-up, 207 (16.9%) women had a late-life dementia event. Compared with women with the highest grip strength (Quartile [Q] 4, 25.8kg), those with the lowest grip strength (Q1, 16.0kg) had greater hazard for a late-life dementia event (HR 2.27 95% CI 1.54-3.35, P<0.001). For TUG, the slowest women (Q4, 12.4 vs. Q1, 7.4s) also recorded a greater hazard for a late-life dementia event (HR 2.10 95% CI 1.42-3.10, P=002). Weak hand grip (<22kg) or slow TUG (>10.2s) provided independent information to the presence of an APOE ℇ 4 allele (n=280, 22.9%). Compared with women with no weakness and no APOE ℇ 4 allele, those with weakness and APOE ℇ 4 allele had a greater hazard (HR 3.19 95% CI 2.09-4.88, P<0.001) for a late-life dementia event. Women presenting with slowness and the APOE ℇ 4 allele also recorded a greater hazard for a late-life dementia event (HR 2.59 95% CI 1.64-4.09, P<0.001). For 5-year muscle function changes, compared with women with the lowest performance decrement (Q1), those with the largest decrement (Q4) had higher hazards for a late-life dementia event (grip strength HR 1.94 95% CI 1.22-3.08, P=0.006; TUG HR 2.52 95% CI 1.59-3.98, P<0.001) over the next 9.5years. Weaker grip strength and slower TUG, and a greater decline over 5years, were significant risk factors for a late-life-dementia event in community-dwelling older women, independent of lifestyle and genetic risk factors. Incorporating muscle function measures as part of dementia screening appears useful to identify high-risk individuals who might benefit from primary prevention programmes.