Impaired Lung Function, Lung Disease, and Risk of Incident Dementia.
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ABSTRACT:
SUBMITTER: Lutsey PL
PROVIDER: S-EPMC6543713 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia.ObjectiveTo prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia.MethodsIn the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 < 80% predicted) and in participants with COPD (FEV1/FVC < 0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80% predicted). Hazard ratios (HRs) with 95% confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype.ResultsOf 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95% CI, 1.53-4.75; adjusted HRCOPD 1.03; 95% CI, 0.61-1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC% predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95% CI, 1.31-3.98), as well as Alzheimer's disease (AD; adjusted HR 2.13; 95% CI, 1.13-4.02).ConclusionParticipants with PRISm or a low FVC% predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC% predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.
| S-EPMC8385522 | biostudies-literature
Project description:BACKGROUND:Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012. PREDICTORS:Race- and sex-specific quartiles of percent-predicted forced vital capacity (FVC) and the proportion of forced expiratory volume in 1 second of expiration to FVC (FEV1/FVC) at baseline determined with spirometry. OUTCOMES:Incident ESRD (defined here as renal replacement therapy or death due to CKD) as the primary outcome and incident CKD (defined here as ESRD, ?25% decline in estimated glomerular filtration rate to a level <60mL/min/1.73m2, or CKD-related hospitalizations/deaths) as the secondary outcome. RESULTS:During a median follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting for potential confounders, the cause-specific HR of incident ESRD for the lowest (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and 1.33 (95% CI, 1.03-1.73) for FEV1/FVC. Compared to a high-normal lung function pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV1/FVC<70%; 3.4% of participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28 (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted FVC<80% and FEV1/FVC?70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81), obstructive pattern (ie, percent-predicted FVC?80% and FEV1/FVC<70%; 18.9% of participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent-predicted FVC 80%-<100% and FEV1/FVC?70%, or percent-predicted FVC?80% and FEV1/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD. LIMITATIONS:Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline. CONCLUSIONS:Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.
| S-EPMC5651181 | biostudies-literature
Project description:Background: Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP), particularly in DNMT3A, TET2, and JAK2, are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. However, whether CHIP is associated with increased risk of peripheral artery disease (PAD) remains unknown. In addition, chemotherapy frequently causes mutations in DNA Damage Repair (DDR) genes TP53 and PPM1D, and whether CHIP caused by somatic mutations in DDR genes results in increased risk of atherosclerosis is unclear. We sought to test whether CHIP, and CHIP caused by DDR genes, associates with incident peripheral artery disease (PAD) and atherosclerosis. Methods: We identified CHIP among 50,122 exome sequences in individuals from UK and Mass General Brigham Biobanks and tested CHIP status (N=2,851) with incident PAD and atherosclerosis across multiple arterial beds. To mimic the human scenario of clonal hematopoiesis and test whether the expansion of p53-deficient hematopoietic cells contributes to atherosclerosis, a competitive bone marrow transplantation (BMT) strategy was used to generate atherosclerosis-prone Ldlr-/- chimeric mice carrying 20% Trp53-/- hematopoietic cells (20% KO-BMT mice). We then evaluated aortic plaque burden and plaque macrophage accumulation 12 weeks after grafting. Results: CHIP associated with incident PAD (HR 1.7; P=2.2x10-5) and atherosclerosis in multiple beds (HR 1.3; P=9.7x10-5), with increased risk among individuals with DDR CHIP (HR 2.0; P=0.0084). Among atherosclerosis-prone Ldlr null mice, the p53 -/- 20% KO-BMT mice demonstrated increased aortic plaque size (p=0.013) and accumulation of p53-/- plaque macrophages (P<0.001), driven by an abundance of p53-deficient plaque macrophages. The expansion of p53-deficient cells did not affect the expression of the pro-inflammatory cytokines IL-6 and IL-1β in the atherosclerotic aortic wall. Conclusions: Our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system, with evidence of increased plaque among p53 -/- 20% KO-BMT mice via expansion of plaque macrophages. These observations provide new insight into the link between CHIP and cardiovascular disease, and lend human genetic support to the concept that post-cytotoxic chemotherapy patients may benefit from surveillance for atherosclerotic conditions in addition to therapy-related myeloid neoplasms.
2022-11-29 | GSE184420 | GEO
Project description:BACKGROUND:Although the prevalence of kidney disease is higher in those with reduced lung function, the longitudinal relationship between low lung function and future risk of chronic kidney disease (CKD) has not been widely explored. METHODS:Baseline lung function was assessed in 20,700 men and 7325 women from 1974 to 1992. Mean age was 43.4 (±6.6) and 47.5 (±7.9) for men and women respectively. Sex-specific quartiles of FEV1 and FVC (L) were created (Q4: highest, reference) and the cohort was also divided by the FEV1/FVC ratio (? or?<?0.70). Cox proportional hazards regression was used to determine the risk of incident CKD events (inpatient or outpatient hospital diagnosis of CKD) in relation to baseline lung function after adjustment for various confounding factors. RESULTS:Over 41?years of follow-up there were 710 and 165 incident CKD events (main diagnosis) in men and women respectively. Low FEV1 was strongly associated with future risk of CKD in men (Q1 vs Q4 adjusted HR: 1.46 (CI:1.14-1.89), p-trend 0.002). Similar findings were observed for FVC in men (1.51 (CI:1.16-1.95), p-trend 0.001). The adjusted risks were not found to be significant in women, for either FEV1 or FVC. FEV1/FVC?<?0.70 was not associated with increased incidence of CKD in men or women. CONCLUSION:Low FEV1 and FVC levels at baseline are a risk factor for the development of future incident CKD in men. Monitoring kidney function in those with reduced vital capacity in early life could help with identifying those at increased risk of future CKD.
| S-EPMC7144045 | biostudies-literature
Project description:RationaleChronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.ObjectivesTo test whether albuminuria was associated with lung function decline and incident CLRDs.MethodsSix U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.Measurements and main resultsAmong 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease.ConclusionsAlbuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.
| S-EPMC6363973 | biostudies-literature
Project description:INTRODUCTION:The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD). METHODS:We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts). RESULTS:The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low. DISCUSSION:Our results reinforce the diagnostic importance of AD pathology in clinical AD. Further harmonization of assessment approaches for vascular pathologies is required.
| S-EPMC5466467 | biostudies-literature
Project description:Higher serum phosphorous is associated with cerebral small vessel disease, an important driver of cognitive decline and dementia. Whether serum phosphorous, a potentially modifiable parameter, associates with risk of incident dementia is not known. We aimed to examine the association between serum phosphorous and risk of incident dementia and to determine if the association is modified by age. We used the United States Department of Veterans Affairs national databases to build a longitudinal observational cohort of US veterans without prior history of dementia and with at least one outpatient serum phosphorus between October 2008 and September 2010 and followed them until September 2014. Serum phosphorus was categorized into quintiles: ?2.9, >2.9 to ?3.2, >3.2 to ?3.5, >3.5 to ?3.9, >3.9 mg/dL. There were 744,235 participants in the overall cohort. Over a median follow-up of 5.07 years (Interquartile range [IQR]: 4.28, 5.63), adjusted Cox models show that compared to quintile 2, the risk of incident dementia was increased in quintile 4 (Hazard Ratio [HR] = 1.05; CI = 1.01-1.10) and quintile 5 (HR = 1.14; CI = 1.09-1.20). In cohort participants ?60 years old, the risk of incident dementia was increased in quintile 4 (HR = 1.29; CI = 1.12-1.49) and 5 (HR = 1.45; CI = 1.26-1.68). In participants > 60 years old, the risk was not significant in quintile 4, and was attenuated in quintile 5 (HR = 1.10; CI = 1.05-1.16). Formal interaction analyses showed that the association between phosphorous and dementia was more pronounced in those younger than 60, and attenuated in those older than 60 (P for interaction was 0.004 and <0.0001 in quintiles 4 and 5; respectively). We conclude that higher serum phosphorous is associated with increased risk of incident dementia. This association is stronger in younger cohort participants. The identification of serum phosphorous as a risk factor for incident dementia has public health relevance and might inform the design and implementation of risk reduction strategies.
| S-EPMC5289565 | biostudies-literature
Project description:Introduction: Little is known about risk factors of dementia in Latin American countries. We aimed to identify socio-demographic, health and lifestyle risk factors of incident dementia in Cuban older adults. Methods: Data were from 1,846 participants in the Cuban cohort of the 10/66 Dementia Research Group. Participants completed questionnaires, health examinations, and cognitive tests at baseline (2003-2006) and 4.5 years later (2007-2010). Associations between risk factors (baseline) and incident dementia (follow-up) were examined using logistic regression. Results: Just over 9% of participants developed dementia. Overall, older age and low physical activity were associated with incident dementia. In those 65-74 years of age, depression, stroke and low physical activity were associated with incident dementia. In those ?75 years of age, low physical activity, never eating fish, and smoking were associated with incident dementia. Conclusions: Modifiable lifestyle factors play an important role in developing dementia in Cuban older adults. This knowledge opens up opportunities for preventive strategies.
| S-EPMC7511701 | biostudies-literature
Project description:ObjectiveTo compare incident dementia risk among patients who initiated treatment with metformin or sulfonylurea in Veterans Health Affairs (VHA) patients with replication in Kaiser Permanente Washington (KPW) patients to determine whether first-choice antidiabetic medications are associated with reduced risk of dementia.Patients and methodsCohorts contained 75,187 VHA patients and 10,866 KPW patients, 50 years and older, who initiated monotherapy with metformin or sulfonylurea. Patients were free of dementia diagnoses and any diabetes treatment for 2 years before cohort entry. Variables were extracted from electronic health data from VHA (1999-2015) and KPW (1996-2015), which included diagnosis codes, pharmacy data, laboratory values, and demographic characteristics. Propensity scores and inverse probability of treatment weighting controlled for confounding.ResultsVeterans Health Affairs patients were 60.8±6.8 years of age on average, and KPW patients were 63.1±9.5 years of age. In the VHA sample, 72,769 (96.8%) were male; and in the KPW sample, 5480 (50.4%). After adjusting for confounding, metformin initiation was associated with a significantly (P=.02) lower risk of dementia in VHA (hazard ratio, 0.9; 95% CI, 0.9-1.0), with a similar point estimate in KPW (hazard ratio, 0.9; 95% CI, 0.7-1.1). Metformin was not associated with dementia risk in patients 75 years and older.ConclusionExisting epidemiological studies of metformin and incident dementia have been inconsistent. Using a similar study design in 2 patient populations that differed in clinical and demographic characteristics, our results provide robust evidence that metformin use is associated with a modestly lower risk of incident dementia.
| S-EPMC7029783 | biostudies-literature
Project description:BackgroundAssociations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR). However, whether there is a graded increase in dementia risk for worse eGFR in each ACR category is unclear. Also, whether genetic risk for dementia impacts the associations is unknown. The current study aims to investigate the associations between eGFR and albuminuria with dementia risk both individually and jointly, whether the associations vary by different follow-up periods, and whether genetic factors modified the associations.MethodsIn 202,702 participants aged ≥ 60 years from the UK Biobank, Cox proportional-hazards models were used to examine the associations between eGFR and urine albumin creatinine ratio (ACR) with risk of incident dementia. GFR was estimated based on serum creatinine, cystatin C, or both. The models were restricted to different follow-up periods (< 5 years, 5-10 years, and ≥ 10 years) to investigate potential reverse causation.ResultsOver 15 years of follow-up, 6,042 participants developed dementia. Decreased kidney function (eGFR < 60 ml/min/1.73m2) was associated with an increased risk of dementia (Hazard Ratio [HR] = 1.42, 95% Confidence Interval [CI] 1.28-1.58), compared to normal kidney function (≥ 90 ml/min/1.73m2). The strength of the association remained consistent when the models were restricted to different periods of follow-up. The HRs for incident dementia were 1.16 (95% CI 1.07-1.26) and 2.24 (95% CI 1.79-2.80) for moderate (3-30 mg/mmol) and severely increased ACR (≥ 30 mg/mmol) compared to normal ACR (< 3 mg/mmol). Dose-response associations were observed when combining eGFR and ACR, with those in the severest eGFR and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34-9.43). APOE status significantly modified the association (p = 0.04), with stronger associations observed among participants with a lower genetic risk of dementia. There was no evidence of an interaction between kidney function and non-APOE polygenic risk of dementia with dementia risk (p = 0.42).ConclusionsKidney dysfunction and albuminuria were individually and jointly associated with higher dementia risk. The associations were greater amongst participants with a lower genetic risk of dementia based on APOE, but not non-APOE polygenic risk.
| S-EPMC10440913 | biostudies-literature