Interleukin 6 plasma concentration associates with cognitive decline: the northern Manhattan study.
ABSTRACT: Interleukin 6 (IL-6) is an inflammatory cytokine that has been associated with vascular disease and cognitive impairment, but few studies have examined these relationships in population-based studies that include Hispanic and Black people who often have a greater prevalence of vascular risk factors and are at an elevated risk of dementia than Whites. We examined relative elevations of plasma IL-6 concentrations in relation to cognitive decline in a stroke-free racially/ethnically diverse community-based sample from Northern Manhattan.We used mixed effects models to measure the effect of IL-6 on change in performance on the modified Telephone Interview for Cognitive Status (TICS-m) measured annually in our cohort, adjusting for sociodemographic and vascular risk factors.There were 1,224 participants with IL-6 levels (median 1.5 pg/ml, interquartile range 0.83-2.57 pg/ml) and TICS-m data available (mean = 31.6 points, SD 6.5). The mean age was 71 (SD 9.3; 64% women, 59% Hispanic, 19% Black, 19% White) with 3,406 person-years and a median 3.0 years of follow-up (interquartile range 1.1-4.0 years). Participants with IL-6 levels above the median showed greater cognitive decline on the TICS-m compared to those with levels below the median, adjusting for sociodemographic and vascular factors (β = -0.17 points/year, p = 0.02). Decline on the TICS-m among participants with IL-6 above the median differed by age (p for interaction <0.001). There was no interaction by race/ethnicity, vascular risk factors, C-reactive protein, apolipoprotein ε4 allele status, or the metabolic syndrome among nondiabetics.IL-6 associated with cognitive decline among older participants in this racially/ethnically diverse sample independent of other vascular risk factors and C-reactive protein.
Project description:Brain magnetic resonance imaging (MRI) allows researchers to observe structural pathology that may predict cognitive decline. Some populations are less accessible through traditional in-person visits, and may be under-represented in the literature.We examined white matter hyperintensity volume (WMHV) and cerebral parenchymal fraction (CPF) as predictors of cognitive decline measured by a modified Telephone Interview for Cognitive Status (TICS-m) in the Northern Manhattan Stroke Study, a racially and ethnically diverse cohort study. Participants were stroke-free, above 50 years old, and had no contraindications to MRI. A total of 1143 participants had MRI and TICS-m data available [mean age 70 (SD=9), 61% women, 66% Hispanic, 17% Black, 15% white].Those in the third and fourth quartiles of WMHV had significantly greater decline in TICS-m over time as compared with those in the first quartile (Q3: -0.17 points/year, Q4: -0.30 points/year). Those in the bottom 2 quartiles of CPF had significantly greater decline in TICS-m than those in the top quartile (Q1: -0.3 points/year, Q2: -0.2 points/year). Apolipoprotein E (APOE) e4 allele carriers had greater cognitive decline per unit of CPF. Those with greater CPF preserve TICS-m performance better despite greater WMHV.Telephone cognitive assessments can detect decline due to white matter lesions and smaller brain volumes.
Project description:To evaluate the effects of vascular conditions and education quality on cognition over time in White and African American (AA) older adults.We investigated cross-sectional and longitudinal racial differences in executive functioning (EF) and memory composites among Whites (n = 461) and AAs (n = 118) enrolled in a cohort study. We examined whether cerebrovascular risk factors and Shipley Vocabulary scores (a proxy for education quality) accounted for racial differences.On average, AAs had lower quality of education and more cerebrovascular risk factors including hypertension, diabetes, and obesity. AAs had lower mean EF and memory at baseline, but there were no group differences in rates of decline. Cross-sectional racial differences in EF and memory persisted after controlling for vascular disease, but disappeared when controlling for Shipley Vocabulary.Quality of education appears to be more important than cerebrovascular risk factors in explaining cross-sectional differences in memory and EF performance between White and AA older adults. Further investigation is needed regarding the relative contribution of education quality and cerebrovascular risk factors to cognitive decline among ethnically/racially diverse older adults.
Project description:OBJECTIVES:Blacks and Hispanics are at increased risk for dementia, even after socioeconomic and vascular factors are taken into account. This study tests a comprehensive model of psychosocial pathways leading to differences in longitudinal cognitive outcomes among older blacks and Hispanics, compared to non-Hispanic whites. METHODS:Using data from 10,173 participants aged 65 and older in the Health and Retirement Study, structural equation models tested associations among race/ethnicity, perceived discrimination, depressive symptoms, external locus of control, and 6-year memory trajectories, controlling for age, sex, educational attainment, income, wealth, and chronic diseases. RESULTS:Greater perceived discrimination among blacks was associated with lower initial memory level via depressive symptoms and external locus of control, and with faster memory decline directly. Greater depressive symptoms and external locus of control among Hispanics were each independently associated with lower initial memory, but there were no pathways from Hispanic ethnicity to memory decline. DISCUSSION:Depression and external locus of control partially mediate racial/ethnic differences in memory trajectories. Perceived discrimination is a major driver of these psychosocial pathways for blacks, but not Hispanics. These results can inform the development of policies and interventions to reduce cognitive morbidity among racially/ethnically diverse older adults.
Project description:OBJECTIVES:To test associations between subclinical brain infarcts (SBIs) and functional decline independently of intervening clinical vascular events and other vascular risk factors. DESIGN:Longitudinal follow-up for a mean 7.3 years. Generalized estimating equation models were used to test associations between SBIs, number of perivascular spaces (PVSs), baseline Barthel Index (BI), and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors and for stroke and myocardial infarction occurring during follow-up. SETTING:Population-based prospective cohort study. PARTICIPANTS:Stroke-free individuals from the racially and ethnically diverse Northern Manhattan Study (N=1,290). MEASUREMENTS:Annual functional assessments using the BI (range 0-100). RESULTS:Mean age was 70.6?±?9.0, 40% of participants were male, 66% were Hispanic, 193 (16%) had SBIs, and 508 (42%) had large PVSs. SBIs were not associated with baseline BI. In a fully adjusted model, there was a change in BI of -0.85 points per year (95% confidence interval (CI)=-1.01 to -0.69); those with SBI had an additional change in BI 0f -0.88 points (95% CI=-1.43 to -0.32). There were no associations between PVS and baseline BI or change in BI. CONCLUSION:In a large population-based study, we found a strong and independent association between "subclinical" markers of cerebrovascular injury and important clinical, person-centered functional trajectories. Future research could clarify the evolution of such subclinical markers over time and test strategies to prevent their progression and minimize related disability. J Am Geriatr Soc 66:2144-2150, 2018.
Project description:To examine the performance of the Telephone Interview for Cognitive Status (TICS) for identifying participants appropriate for trials of physical activity and cognitive training interventions.Volunteers (N=343), ages 70-85 years, who were being recruited for a pilot clinical trial on approaches to prevent cognitive decline, were administered TICS and required to score ? 31 prior to an invitation to attend clinic-based assessments. The frequencies of contraindications for physical activity and cognitive training interventions were tallied for individuals grouped by TICS scores. Relationships between TICS scores and other measures of cognitive function were described by scatterplots and correlation coefficients.Eligibility criteria to identify candidates who were appropriate candidates for the trial interventions excluded 51.7% of the volunteers with TICS<31. TICS scores above this range were not strongly related to cognition or attendance at screening visits, however overall enrollment yields were approximately half for participants with TICS=31 versus TICS=41, and increased in a graded fashion throughout the range of scores.Use of TICS to define eligibility criteria in trials of physical activity and cognitive training interventions may not be worthwhile in that many individuals with low scores would already be eliminated by intervention-specific criteria and the relationship of TICS with clinic-based tests of cognitive function among appropriate candidates for these interventions may be weak. TICS may be most useful in these trials to identify candidates for oversampling in order to obtain a balanced cohort of participants at risk for cognitive decline.
Project description:BACKGROUND:Cerebral white matter hyperintensities (WMHs) on MRI are common and associated with vascular and functional outcomes. However, the relationship between WMHs and longitudinal trajectories of functional status is not well characterized. We hypothesized that whole brain WMHs are associated with functional decline independently of intervening clinical vascular events and other vascular risk factors. METHODS AND FINDINGS:In the Northern Manhattan Study (NOMAS), a population-based racially/ethnically diverse prospective cohort study, 1,290 stroke-free individuals underwent brain MRI and were followed afterwards for a mean 7.3 years with annual functional assessments using the Barthel index (BI) (range 0-100) and vascular event surveillance. Whole brain white matter hyperintensity volume (WMHV) (as percentage of total cranial volume [TCV]) was standardized and treated continuously. Generalized estimating equation (GEE) models tested associations between whole brain WMHV and baseline BI and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors, as well as stroke and myocardial infarction (MI) occurring during follow-up. Mean age was 70.6 (standard deviation [SD] 9.0) years, 40% of participants were male, 66% Hispanic; mean whole brain WMHV was 0.68% (SD 0.84). In fully adjusted models, annual functional change was -1.04 BI points (-1.20, -0.88), with -0.74 additional points annually per SD whole brain WMHV increase from the mean (-0.99, -0.49). Whole brain WMHV was not associated with baseline BI, and results were similar for mobility and non-mobility BI domains and among those with baseline BI 95-100. A limitation of the study is the possibility of a healthy survivor bias, which would likely have underestimated the associations we found. CONCLUSIONS:In this large population-based study, greater whole brain WMHV was associated with steeper annual decline in functional status over the long term, independently of risk factors, vascular events, and baseline functional status. Subclinical brain ischemic changes may be an independent marker of long-term functional decline.
Project description:We hypothesized that infectious burden (IB), a composite serologic measure of exposure to common pathogens (i.e., Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) associated with vascular risk in the prospective Northern Manhattan Study (NOMAS), would also be associated with cognition.Cognition was assessed using the Mini-Mental State Examination (MMSE) at enrollment and the modified Telephone Interview for Cognitive Status (TICS-m) at annual follow-up visits. Adjusted linear and logistic regressions were used to measure the association between IB index and MMSE. Generalized estimating equation models were used to evaluate associations with TICS-m and its change over time.Serologies and cognitive assessments were available in 1,625 participants of the NOMAS cohort. In unadjusted analyses, higher IB index was associated with worse cognition (change per standard deviation [SD] of IB for MMSE was -0.77, p < 0.0001, and for first measurements of TICS-m was -1.89, p < 0.0001). These effects were attenuated after adjusting for risk factors (for MMSE adjusted change per SD of IB = -0.17, p = 0.06, for TICS-m adjusted change per SD IB = -0.68, p < 0.0001). IB was associated with MMSE ?24 (compared to MMSE >24, adjusted odds ratio 1.26 per SD of IB, 95% confidence interval 1.06-1.51). IB was not associated with cognitive decline over time. The results were similar when IB was limited to viral serologies only.A measure of IB associated with stroke risk and atherosclerosis was independently associated with cognitive performance in this multiethnic cohort. Past infections may contribute to cognitive impairment.
Project description:Prior evidence suggested that inflammation and inflammatory cytokines polymorphisms might be essential in the development of coronary heart disease (CHD) and cognitive decline. The following study investigated the associations between interleukin-35 (IL-35) polymorphisms and cognitive decline in CHD patients over a 2-year period.CHD patients were enrolled between January 2015 and January 2016. Cognitive function, including memory, orientation, verbal and attention were assessed using Telephone Interview for Cognitive Status-Modified (TICS-m) during a 2-year follow-up. Genotypes of the single nucleotide polymorphisms (SNPs), including rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 and rs393581 of IL-35 were examined by MassArray (Sequenom). The differences of TICS-m score between 2-year interval were used to estimate the cognitive decline; linear regression model was used to analyze the association between IL-35 polymorphisms and cognitive decline in CHD patients after a 2-year follow-up.The mean age of study individuals was 60.58 (±7.86) years old. There were 255 (68.5%) males and 117 (31.5%) female patients. The TICS-m scores, including overall cognition score, verbal attention and memory scores gradually decreased over a 2 year follow up period (P?<?.001, respectively), whereas there was no difference in orientation function score between the 1-year and 2-year follow-up (P?=?.448). Furthermore, after adjusting for age, sex, history of hypertension(HT) and Diabetes mellitus(DM), smoking, education, Therapy regimen (PCI, CABG, medication) left ventricular ejection fraction (LVEF), and the severity of coronary artery stenosis (Gensini score), no association was found between IL-35 rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 genotypes and cognitive decline in CHD patients over a 2-year period.Our data reveled that IL-35 polymorphisms was not associated with cognitive decline in CHD patients over a 2-year period. Yet, further studies are needed to confirm the role of cytokine gene polymorphisms in cognitive decline among CHD patients.
Project description:To examine fibroblast growth factor 23 (FGF23) as a risk factor for incident stroke in a racially/ethnically diverse population-based urban cohort.Stroke-free Northern Manhattan Study participants with FGF23 measurements (n = 2,525) were followed for a mean of 12 (±5) years to detect incident strokes. We used Cox proportional hazards models to estimate the association of baseline FGF23 with incident total, ischemic, and hemorrhagic stroke.Median FGF23 was 57 relative units (RU)/mL (interquartile range = 44-81 RU/mL). Each unit increase of natural log-transformed FGF23 conferred a 40% greater overall stroke risk after adjusting for estimated glomerular filtration rate and sociodemographic and vascular risk factors (hazard ratio = 1.4, 95% confidence interval 1.1-1.6, p = 0.004). Penalized spline analysis revealed a linear association with overall stroke risk at ?90 RU/mL FGF23, compared with <90 RU/mL (hazard ratio = 1.5, 95% confidence interval = 1.2-2.1, p = 0.004). Greater FGF23 conferred a doubling of intracerebral hemorrhage (ICH) risk but no significant increased risk of ischemic stroke. The associations of elevated FGF23 levels with greater risks of overall stroke and ICH events were independent of phosphate and parathyroid hormone levels and were similar among participants without chronic kidney disease.Elevated FGF23 was a risk factor for overall stroke and ICH events, in particular in a racially and ethnically diverse urban community, independent of chronic kidney disease.
Project description:An elevated fibroblast growth factor (FGF) 23 is an independent risk factor for cardiovascular disease and mortality in patients with kidney disease. The relationship between FGF23 and cause-specific mortality in the general population is unknown.To investigate the association of elevated FGF23 with the risk of cause-specific mortality in a racially and ethnically diverse urban general population.The Northern Manhattan Study is a population-based prospective cohort study. Residents who were > 39 years old and had no history of stroke were enrolled between 1993 and 2001. Participants with available blood samples for baseline FGF23 testing were included in the current study (n = 2525).Cause-specific death events.A total of 1198 deaths (474 vascular, 612 nonvascular, 112 unknown cause) occurred during a median follow-up of 14 years. Compared to participants in the lowest FGF23 quintile, those in the highest quintile had a 2.07-fold higher risk (95% confidence interval [CI], 1.45, 2.94) of vascular death and a 1.64-fold higher risk (95% CI, 1.22, 2.20) of nonvascular death in fully adjusted models. Higher FGF23 was independently associated with increased risk of mortality due to cancer, but only in Hispanic participants (hazard ratio per 1 unit increase in ln FGF23 of 1.87; 95% CI, 1.40, 2.50; P for interaction = .01).Elevated FGF23 was independently associated with increased risk of vascular and nonvascular mortality in a diverse general population and with increased risk of cancer death specifically in Hispanic individuals.