Decline In Middle-aged Adults Research Articles

Urine Epidermal Growth Factor and Kidney Function Decline in Middle-Aged Adults

Urine Epidermal Growth Factor and Kidney Function Decline in Middle-Aged Adults

288 Urine epidermal growth factor and kidney function decline in middle-aged adults

288 Urine epidermal growth factor and kidney function decline in middle-aged adults

The influence of intergenerational support on cognitive functioning among middle-aged Chinese: Moderation by personal income

ObjectiveTo analyze the effects of personal income on the relationship between intergenerational support (IS) and cognitive functioning. MethodsData were obtained from four waves of nationally representative surveys of the 2011–2018 China Health and Retirement Longitudinal Study (CHARLS), involving 8,207 participants aged 45 ∼ 60 at baseline. Multivariate linear regression models using generalized estimating equations were used to analyze the effects of three forms of intergenerational mutual supports on cognitive functioning in middle-aged adults, and subgroup regressions were used to analyze the moderating role of personal income in this relationship. ResultsThe results showed that financial and caregiving support from children impaired the cognitive functioning of their parents; whereas providing financial support to children and mutual emotional support with them positively affected their cognition; however, childcare was not significantly associated with cognitive levels in middle-aged adults. Moreover, the effect of IS on the cognitive level of Chinese middle-aged people disappeared or was attenuated by having pensions or earning their own post-tax income. ConclusionIS has a significant effect on cognitive functioning in middle-aged adults, but this effect is moderated by personal income. These results are informative for the development of intergenerational relationship intervention programs for the prevention of cognitive decline in middle-aged adults with different personal income.

Turning and sitting movements during timed up and go tests predict deterioration of physical function in middle-aged adults

BackgroundDeterioration of physical function in middle-aged adults is a significant challenge that can lead to increased risk of future falls. However, a screening method for the functional decline in middle-aged adults has not been established. Research questionTo evaluate the relationship between biomechanical parameters assessed by the timed up and go test (TUG) and locomotive syndrome (LS) in middle-aged adults. MethodsThe inclusion criterion was: under 65 years of age. A total of 97 volunteers (mean age 51.1 years) participated in this study. An LS test was performed, including a 2-step test, a stand-up test, and a 25-question Geriatric Locomotive Function Scale. The TUG was measured using inertial measurement units (IMUs) at comfortable and fast speeds. We then determined the minimum values for anterior-posterior acceleration and angular velocity around the medial-lateral axis, as well as the maximum values of angular velocity around the vertical axis for the upper trunk and sacrum in a TUG phase. ResultsAngular velocity around the vertical axis for upper trunk and sacrum were significantly smaller in LS than non-LS in the turn phase of both speed conditions. For the fast speed condition, the minimum anterior-posterior acceleration for sacrum was greater in LS than in the non-LS condition for the stand-to-sit phase. Angular velocity around the vertical axis for turning and anterior-posterior acceleration from sitting were associated with detection of LS. SignificanceTurning and sitting movements during TUG should be observed using IMU to screen for physical function decline in middle aged adults.

Potassium and magnesium and cognitive decline in middle-aged adults

BACKGROUND: Increase in dementias globally is a burden to patients, caregivers, the healthcare system, and the communities in which they live. Understanding nutritional patterns and how they may impact the prevention of these conditions will be critical moving forward. The known impact of minerals such as potassium and magnesium on conditions such as hypertension, oxidative stress, and inflammation – all of which directly impact cognitive health – warrant further study as to their potential direct effects on cognitive function. OBJECTIVE: To determine if low potassium and magnesium blood levels and dietary intakes are associated with cognitive decline in middle-aged adults over a 6-year span. METHODS: Linear regression models were used to describe the associations between potassium and magnesium intakes and cognitive function scores of participants in the Atherosclerosis Risk in Communities Study (ARIC) dataset over 6 years of follow up. Associations with blood values were also assessed. Variables controlled for included total HEI score, a measure of dietary quality. 9,044 participants were included. All linear regression models were run with a 95% confidence interval. RESULTS: Levels of blood potassium and magnesium, in univariate as well as in multivariate analysis were found to have no significant association with cognitive decline. Likewise, intake levels of both minerals were shown to have no significant association with cognitive function. CONCLUSIONS: In 9,044 participants, ages 44 to 66, potassium and magnesium intake and blood serum levels were found to have no significant association with cognitive decline in fully controlled models over 6 years in the ARIC cohort.

The association of post-traumatic stress disorder with glomerular filtration rate decline.

While major depression is known to be associated with glomerular filtration rate (GFR) decline, there is a lack of data on the association of other mental illnesses like posttraumatic stress disorder (PTSD) with kidney disease. In 640 adult participants of the Heart and Soul Study (mean baseline age of 66.2 years) with a high prevalence cardiovascular disease, hypertension and diabetes, we examined the association of PTSD with GFR decline over a 5-year follow-up. We observed a significantly greater estimated (e) GFR decline over time in those with PTSD compared to those without (2.97 vs. 2.11 ml/min/1.73 m2 /year; p=.022). PTSD was associated with 91% (95% CI 12%-225%) higher odds of 'rapid' versus 'mild' (>3.0 vs. <3.0ml/min/1.73 m2 /per year) eGFR decline. These associations remained consistent despite controlling for demographics, medical comorbidities, other mental disorders and psychiatric medications. In conclusion, our study provides evidence that PTSD is independently associated with GFR decline in middle-aged adults with a high comorbidity burden. This association needs to be examined in larger cohorts with longer follow-ups.

Association of long-term hyperglycaemia and insulin resistance with brain atrophy and cognitive decline: A longitudinal cohort study.

To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline. We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Time-weighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits. Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference=-1.96 ml, 95% CI: -3.73, -0.18) and executive function decline (adjusted Z score difference=-0.14, 95% CI: -0.23, -0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group. Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline.

Polygenic association of glomerular filtration rate decline in world trade center responders

BackgroundThe factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline.MethodsWe analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3–5-year observation period. eGFR decline was defined in separate analyses as “clinical” (> -1.0 ml/min/1.73 m2/year) or “empirical” (lower most quartile of eGFR slopes).ResultsThe mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD.ConclusionCommon genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

Association of Posttraumatic Stress Disorder With Accelerated Cognitive Decline in Middle-aged Women

Posttraumatic stress disorder (PTSD) has been hypothesized to lead to impaired cognitive function. However, no large-scale studies have assessed whether PTSD is prospectively associated with cognitive decline in middle-aged adults. To assess the association between PTSD and decline in cognitive function over time. This cohort study included participants from the Nurses' Health Study II, an ongoing longitudinal cohort study involving community-dwelling middle-aged female nurses residing in the US who had at least a 2-year nursing degree at the time of enrollment in 1989. The present study included 12 270 trauma-exposed women who were enrolled in the PTSD substudy of the Nurses' Health Study II and completed 1 to 5 cognitive assessments. Data were collected from March 1, 2008, to July 30, 2019. Lifetime PTSD symptoms, assessed using a validated questionnaire between March 1, 2008, and February 28, 2010. The main outcome was evaluated using the Cogstate Brief Battery, a self-administered online cognitive battery. Cognitive function was measured by a psychomotor speed and attention composite score and a learning and working memory composite score. Women completed the Cogstate Brief Battery every 6 or 12 months (up to 24 months) from October 3, 2014, to July 30, 2019. Linear mixed-effects models were used to evaluate the association of PTSD symptoms with the rate of change in cognition over follow-up, considering a broad range of relevant covariates, including the presence of depression symptoms and history of clinician-diagnosed depression. The rate of cognitive change was adjusted for potential practice effects (ie, potential changes in test results that occur when a test is taken more than once) by including indicators for the number of previous tests taken. Among 12 270 women, the mean (SD) age at the baseline cognitive assessment was 61.1 (4.6) years; 125 women (1.0%) were Asian, 75 (0.6%) were Black, 156 (1.3%) were Hispanic, 11 767 (95.9%) were non-Hispanic White, and 147 (1.2%) were of other race and/or ethnicity. A higher number of PTSD symptoms was associated with worse cognitive trajectories. Compared with women with no PTSD symptoms, women with the highest symptom level (6-7 symptoms) had a significantly worse rate of change in both learning and working memory (β = -0.08 SD/y; 95% CI, -0.11 to -0.04 SD/y; P < .001) and psychomotor speed and attention (β = -0.05 SD/y; 95% CI, -0.09 to -0.01 SD/y; P = .02), adjusted for demographic characteristics. Associations were unchanged when additionally adjusted for behavioral factors (eg, 6-7 symptoms in the analysis of learning and working memory: β = -0.08 SD/y; 95% CI, -0.11 to -0.04 SD/y; P < .001) and health conditions (eg, 6-7 symptoms in the analysis of learning and working memory: β = -0.08 SD/y; 95% CI, -0.11 to -0.04 SD/y; P < .001) and were partially attenuated but still evident when further adjusted for practice effects (eg, 6-7 symptoms in the analysis of learning and working memory: β = -0.07 SD/y; 95% CI, -0.10 to -0.03 SD/y; P < .001) and comorbid depression (eg, 6-7 symptoms in the analysis of learning and working memory: β = -0.07 SD/y; 95% CI, -0.11 to -0.03 SD/y; P < .001). In this large-scale prospective cohort study, PTSD was associated with accelerated cognitive decline in middle-aged women, suggesting that earlier cognitive screening among women with PTSD may be warranted. Given that cognitive decline is strongly associated with subsequent Alzheimer disease and related dementias, better understanding of this association may be important to promote healthy aging.

Exposure to household air pollution over 10 years is related to asthma and lung function decline

We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione S-transferase (GST) gene variants, ventilation and atopy. Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions. We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the GSTP1 Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation. Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.

Non-Alcoholic Fatty Liver Disease, and the Underlying Altered Fatty Acid Metabolism, Reveals Brain Hypoperfusion and Contributes to the Cognitive Decline in APP/PS1 Mice.

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease, is associated with cognitive decline in middle-aged adults, but the mechanisms underlying this association are not clear. We hypothesized that NAFLD would unveil the appearance of brain hypoperfusion in association with altered plasma and brain lipid metabolism. To test our hypothesis, amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice were fed a standard diet or a high-fat, cholesterol and cholate diet, inducing NAFLD without obesity and hyperglycemia. The diet-induced NAFLD disturbed monounsaturated and polyunsaturated fatty acid (MUFAs, PUFAs) metabolism in the plasma, liver, and brain, and particularly reduced n-3 PUFAs levels. These alterations in lipid homeostasis were associated in the brain with an increased expression of Tnfα, Cox2, p21, and Nox2, reminiscent of brain inflammation, senescence, and oxidative stress. In addition, compared to wild-type (WT) mice, while brain perfusion was similar in APP/PS1 mice fed with a chow diet, NAFLD in APP/PS1 mice reveals cerebral hypoperfusion and furthered cognitive decline. NAFLD reduced plasma β40- and β42-amyloid levels and altered hepatic but not brain expression of genes involved in β-amyloid peptide production and clearance. Altogether, our results suggest that in a mouse model of Alzheimer disease (AD) diet-induced NAFLD contributes to the development and progression of brain abnormalities through unbalanced brain MUFAs and PUFAs metabolism and cerebral hypoperfusion, irrespective of brain amyloid pathology that may ultimately contribute to the pathogenesis of AD.

The Healthy Brain Project: An Online Platform for the Recruitment, Assessment, and Monitoring of Middle-Aged Adults at Risk of Developing Alzheimer's Disease.

Characterizing the earliest demonstrable cognitive decline in middle-aged adults at risk of Alzheimer's disease (AD) will allow for the better understanding of the early disease trajectory, and the provision of therapies prior to clinical symptom onset. We developed an online platform- healthybrainproject.org.au (Healthy Brain Project; HBP)- to recruit, assess, and monitor at-risk middle-aged adults. Describe the HBP methodology and report baseline characteristics and adherence indices of participants. Between February 2017 and August 2018, 4,000 community-based middle-aged Australian adults with a first or second-degree family history of dementia enrolled at our website (healthybrainproject.org.au). Participants were directed to complete five modules: "Basics", "Health History", "How You Feel", "How You Live", and "How You Think". Of these, 1,816 participants have received a saliva sampling kit for genetic analysis. Participants had a mean (SD) age of 55.5 (6.8) years, 11.8 (3.4) years of education, and annual personal income of AUD$68,830 ($35,044). Participants took 26.4 (49.7) days after enrolment to complete questionnaires and cognitive tests. Most participants were from Victoria (63%), followed by New South Wales (14%). Most participants (74%) were female and 76% identified as Caucasian. Approximately 36% of participants completed all modules (n = 1,450), and 56% (n = 2,221) completed 4 out of 5 modules. Most saliva kits (89%) had been returned. The HBP joins a handful of online registries worldwide that assess and monitor a large cohort of individuals at risk of AD. Our study extends on these efforts by focusing on midlife, where the earliest signs of cognitive and pathological changes will manifest.

Sensorineural Impairments, Cardiovascular Risk Factors, and 10-Year Incidence of Cognitive Impairment and Decline in Midlife: The Beaver Dam Offspring Study.

Sensorineural impairments and cardiovascular risk factors (CVRF) and disease (CVD) in midlife may be important predictors of future cognitive health, but longitudinal studies that include multiple sensorineural measures in middle-aged adults are lacking. Hearing, vision, and olfaction, and CVRF and CVD were measured at the Beaver Dam Offspring Study baseline (2005-2008) examination. The Mini-Mental State Examination and Trail Making Tests A and B were administered at all phases and additional cognitive function measures were obtained at 5 (2010-2013) and 10 years (2015-2017). Cox proportional hazards models were used to evaluate associations between baseline sensorineural impairments, CVRF, CVD, and 10-year cumulative incidence of cognitive impairment and decline. There were 2,556 participants (22-84 years) without cognitive impairment at baseline and data from at least one follow-up. In a multivariable model including age, sex, education, and head injury, visual impairment (hazard ratio = 2.59, 95% confidence interval = 1.34, 5.02), olfactory impairment (hazard ratio = 3.18, 95% confidence interval = 1.53, 6.59), CVD (hazard ratio = 2.37, 95% confidence interval = 1.24, 4.52), and not consuming alcohol in the past year (hazard ratio = 2.21, 95% confidence interval = 1.16, 4.19) were associated with the 10-year cumulative incidence of cognitive impairment. Current smoking and diabetes were associated with increased risk, and exercise with decreased risk, of 10-year decline in cognitive function. Visual and olfactory impairments, CVRF, and CVD were associated with the 10-year cumulative incidence of cognitive impairment and decline in middle-aged adults. Identifying modifiable factors associated with cognitive decline and impairment in midlife may provide opportunities for prevention or treatment and improve cognitive health later in life.

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. Longitudinal study with six years follow-up. Community based. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Flavonol Intake and Cognitive Decline in Middle-Aged Adults.

Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45-64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender, education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P<.001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P<.001). The positive association with total flavonols was strongest for the digit symbol subtest (P<.001). In this cohort, flavonol intake was correlated with protected cognitive function over time.

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife.

Amyloid Burden, Neuronal Function, and Cognitive Decline in Middle-Aged Adults at Risk for Alzheimer's Disease

The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 "Decliners" and 101 "Stables") enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9-8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed.

Cardiovascular risk factors and cognitive decline in middle-aged adults.

To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-Revised and the first-letter word fluency (WF) test using letters F, A, and S. In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima-media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.