Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The Rancho Bernardo Study.
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ABSTRACT: Evidence of a role for vitamin D (VitD) in cognitive aging is mixed and based primarily on extreme VitD deficiency. We evaluated the association of VitD insufficiency with cognitive function in older, community-dwelling adults living in a temperate climate with year-round sunshine.A population-based longitudinal study of 1,058 adults (median age 75; 62% women) who had cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD) measured in 1997-99 and were followed for up to three additional cognitive function assessments over a 12-year period.Overall, 14% (n?=?145) of participants had VitD insufficiency defined as 25OHD <30?ng/ml. Adjusting for age, sex, education, and season, VitD insufficiency was associated with poorer baseline performance on the Mini-Mental Status Exam (MMSE) (p?=?0.013), Trails Making Test B (Trails B) (p?=?0.015), Category Fluency (p?=?0.006), and Long Term Retrieval (p?=?0.019); differences were equivalent to 5 years of age. For those with VitD insufficiency, the odds of mildly impaired performance at baseline were 38% higher for MMSE (p?=?0.08), 78% higher for Trails B (p?=?0.017), and 2-fold higher for Category Fluency and Long Term Retrieval (both p?=?0.001). VitD insufficiency was not related to the rate of cognitive decline on any test or the risk of developing impaired performance during follow-up.In this population with little VitD deficiency, even moderately low VitD was associated with poorer performance on multiple domains of cognitive function. Low VitD did not predict 12-year cognitive decline. Clinical trials are essential to establish a causal link between VitD and cognitive well-being.
<h4>Background</h4>Evidence of a role for vitamin D (VitD) in cognitive aging is mixed and based primarily on extreme VitD deficiency. We evaluated the association of VitD insufficiency with cognitive function in older, community-dwelling adults living in a temperate climate with year-round sunshine.<h4>Methods</h4>A population-based longitudinal study of 1,058 adults (median age 75; 62% women) who had cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD) measured in 1997-99 ...[more]
Project description:BACKGROUND:Although physical activity has been associated with better cognitive function and reduced dementia risk, its association with cognitive decline in normal aging remains uncertain. OBJECTIVE:To determine whether physical activity in youth and older age are associated with age-related cognitive change. METHODS:Over a period of 27 years, 2,027 community-dwelling adults (mean age 73.5; 60% women) of the Rancho Bernardo Study of Healthy Aging completed up to seven cognitive assessments, including tests of global cognitive function, executive function, verbal fluency, and episodic memory. At each visit, participants reported concurrent physical activity. At baseline (1988- 1992), participants additionally reported physical activity as a teenager and at age 30. For each age period, participants were classified as regularly active (3+ times/week) or inactive. RESULTS:Associations between concurrent physical activity and better cognitive function were stronger with advancing age on all tests, even after accounting for education, health, and lifestyle factors, as well as survival differences (ps?<?0.05). Baseline physical activity did not predict rates of cognitive decline (ps?>?0.40). Individuals who were physically active at age 30 and older age maintained the highest global cognitive function with advancing age (p?=?0.002). CONCLUSION:Regular physical activity is associated with better cognitive function with advancing age. Physical activity in young adulthood may contribute to cognitive reserve, which together with physical activity in later years, may act to preserve cognitive function with age.
Project description:Backgroundphysical activity in older age has been associated with better cognitive function, but the role of earlier life physical activity is less well understood.Objectivedetermine associations between physical activity throughout the lifespan and cognitive function in older age.Designcross-sectional study.Settingthe Rancho Bernardo Study of Healthy Aging in southern California.SubjectsA total of 1,826 community-dwelling men and women (60-99 years) who attended a research visit in 1988-92.Methodsparticipants underwent cognitive testing at older age, and reported physical activity as a teenager, at age 30 years, 50 years and currently. For each time-point, participants were classified as regularly active (3+ times/week) or inactive.Resultsregular physical activity was associated with better cognitive function, with physical activity at older ages showing the strongest associations. Physical activity in older age was associated with better global cognitive function, executive function and episodic memory, regardless of intensity. Intense physical activity in teenage years was associated with better late-life global cognitive function in women. Teenage physical activity interacted with older age physical activity on executive function; those active at both periods performed better than those active at only one period. Similar patterns of associations were observed after excluding individuals with poor health.Conclusionsregular physical activity in older age, regardless of intensity, is associated with better cognitive function. Physical activity in teenage years may enhance cognitive reserve to protect against age-related decline in executive function. Further research is needed to assess the effect of physical activity across the lifespan on healthy brain ageing.
Project description:BackgroundMultimorbidity is associated with increased rate of cognitive decline with age. It is unknown whether social engagement, which is associated with reduced risk of dementia, modifies associations between multimorbidity and cognitive decline.ObjectiveTo examine the associations of multimorbidity with longitudinal cognitive test performance among community-dwelling older adults, and to determine whether associations differed by levels of social engagement.MethodsWe used data from the Rancho Bernardo Study of Healthy Aging, a community-based prospective cohort study. Starting in 1992-1996, participants completed a battery of cognitive function tests at up to 6 study visits over 23.7 (mean = 7.2) years. Multimorbidity was defined as≥2 of 14 chronic diseases. Social engagement was assessed using items based on the Berkman-Syme Social Network Index. Multivariable linear mixed-effects models were used to test associations of multimorbidity and cognitive performance trajectories. Effect measure modification by social engagement was evaluated.ResultsAmong 1,381 participants (mean age = 74.5 years; 60.8% women; 98.8% non-Hispanic White), 37.1% had multimorbidity and 35.1% had low social engagement. Multimorbidity was associated with faster declines in Mini-Mental State Examination (MMSE; β= -0.20; 95% CI -0.35, -0.04), Trail-Making Test Part B (β= 10.02; 95% CI 5.77, 14.27), and Category Fluency (β= -0.42; 95% CI -0.72, -0.13) after adjustment for socio-demographic and health-related characteristics. Multimorbidity was associated with faster declines in MMSE among those with low compared to medium and high social engagement (p-interaction < 0.01).ConclusionsMultimorbidity was associated with faster declines in cognition among community-dwelling older adults. Higher social engagement may mitigate multimorbidity-associated cognitive decline.
Project description:This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up.Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up.Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects.Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test.Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort.
Project description:Interleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality.A prospective cohort study included 1843 participants who attended a research visit in 1984-87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.The mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (± 10.6) years and 25 (± 3.7) Kg/m(2), respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (± IQR) length of follow-up was 15.3 ± 10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33-1.64), 1.38 (95% CI, 1.16-1.65), 1.35 (95% CI, 1.02-1.79), and 1.88 (95% CI, 0.97-3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.
Project description:BackgroundWe examined the associations between dual impairments in visual and hearing acuity and aging-related cognitive decline.MethodsThis was a longitudinal study of adults who had visual and hearing acuity and cognitive function assessed in 1992-1996 and were followed for up to 24 years (mean = 7.3 years), with up to five additional cognitive assessments. Visual impairment was defined as vision worse than 20/40, hearing impairment as pure-tone average thresholds >25 dB. Associations were tested using linear mixed-effects regressions.ResultsOf 1,383 participants, 293 had visual impairment, 990 had a hearing impairment and 251 had both deficits. In fully adjusted models, low visual acuity was associated with poorer Mini-Mental State Examination (MMSE; β = -0.29) and Trail-Making Test Part B (Trails B; β = 13.22) performance, and with faster declines in MMSE (β = -0.12) and Trails B (β = 1.84). The combination of low visual and low hearing acuity was associated with poorer MMSE (β = -0.44) and Trails B (β = 11.20) scores, and with faster declines in MMSE (β = -0.19), Trails B (β = 3.50), and Verbal Fluency Test (VFT; β = -0.14) performance. Associations were similar in men and women.ConclusionImpairments in both vision and hearing are associated with a more rapid decline in cognitive function with aging.
Project description:BackgroundGalectin-3 is a marker of myocardial fibrosis that has been implicated in the pathophysiologic pathway of fibrosis; its association with all-cause and cardiovascular disease (CVD) mortality in a community-based cohort free of baseline CVD has not been reported. Our aim was to determine the association between galectin-3 levels and all-cause and CVD mortality in community-dwelling older adults without known CVD.MethodsWe measured plasma galectin-3 levels in 1,393 Rancho Bernardo Study participants without CVD with a mean age of 70 years. Participants were followed up for a mean of 11 years for coronary heart disease, CVD mortality, and all-cause mortality.ResultsDuring follow-up, 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and renal function, galectin-3 was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase 1.30, 95% CI 1.10-1.53) and all-cause mortality (HR 1.12, 1.01-1.24), but not coronary heart disease (HR 1.09, 0.92-1.30). After further adjusting for N-terminal pro B-type natriuretic peptide, galectin-3 remained an independent predictor (HR 1.24, 1.05-1.47) of CVD mortality. Galectin-3 improved the c statistic (0.847-0.851, P = .003) for prediction of CVD death. Net reclassification improvement (>0) with the addition of galectin-3 was 35% (P < .0001); the integrated discrimination index was also significant (P = .03). Participants with both galectin-3 and N-terminal pro B-type natriuretic peptide above the median had increased risk of CVD death vs those with higher levels of only 1 of these markers (HR 1.74, 1.24-2.43).ConclusionHigher levels of galectin-3 are independently associated with all-cause and CVD mortality among community-dwelling older adults with no known CVD at baseline.
Project description:The purpose of this study was to determine the association between neutrophil gelatinase-associated lipocalin (NGAL) levels and cardiovascular and all-cause mortality in community-dwelling older adults.NGAL is a novel marker best known for its role in rapidly identifying acute kidney injury. Although expressed in atherosclerosis, its association with cardiovascular disease (CVD) in the community has not been reported.We measured plasma NGAL levels in 1,393 Rancho Bernardo Study participants without CVD, mean age 70 years. Participants were followed for a mean time period of 11 years.During follow-up, 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and creatinine clearance, NGAL was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase: 1.33, 95% confidence interval [CI]: 1.12 to 1.57), all-cause mortality (HR: 1.19, 95% CI: 1.07 to 1.32), and a combined cardiovascular endpoint (HR: 1.26, 95% CI: 1.10 to 1.45). After further adjusting for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), NGAL remained an independent predictor of each outcome. NGAL improved the C-statistic (0.835 to 0.842) for prediction of CVD death (p = 0.001). Net reclassification improvement (>0) with the addition of NGAL was 18% (p = 0.02); the integrated discrimination index was also significant (p = 0.01). Participants with NGAL and NT-proBNP above the median had increased risk of CVD death versus those with only NT-proBNP elevated (HR: 1.43, 95% CI: 1.12 to 1.82).Plasma NGAL is a significant predictor of mortality and CVD in community-dwelling older adults, independent of traditional risk factors and kidney function, and adds incremental value to NT-proBNP and CRP. The potential impact of these results includes providing insight into new mechanisms of CVD and the possibility of improving screening, intervention, and prevention.
Project description:Cytoarchitectural brain changes during normal aging remain poorly characterized, and it is unclear whether patterns of brain aging differ by sex. This study used restriction spectrum imaging to examine associations between age and brain microstructure in 147 community-dwelling participants (aged 56-99 years). Widespread associations with age in multiple diffusion compartments, including increased free water, decreased restricted and hindered diffusion, and reduced neurite complexity, were observed in the cortical gray matter, the white matter tracts, and the hippocampus. Age differences in cortical microstructure were largely independent of atrophy. Associations were mostly global, although foci of stronger effects emerged in the fornix, anterior thalamic radiation and commissural fibers, and the medial temporal, orbitofrontal, and occipital cortices. Age differences were stronger and more widespread for women than men, even after adjustment for education, hypertension, and body mass index. Restriction spectrum imaging may be a convenient, noninvasive tool for monitoring changes in diffusion properties that are thought to reflect reduced cellular fractions and neurite density or complexity, which occur with typical aging, and for detecting sex differences in patterns of brain aging.
Project description:The association between body-mass-index (BMI), alcohol consumption and their joint effect in increasing the risk of elevated serum alanine (ALT) and aspartate (AST) is unclear in older community-dwelling adults.To determine the association between alcohol, BMI, and their combined effect with serum ALT and AST in older community-dwelling adults in the United States.A cross-sectional, population-based study in participants (n = 2364) from the Rancho Bernardo Study (54% women; mean age: 70 years, BMI: 25 kg/m(2), alcohol users: 63%) who attended a research visit in 1984-87. BMI was recorded by a trained nurse and alcohol use ascertained by a validated questionnaire. Odds-ratio (OR) and 95% confidence intervals (CI) of elevated serum ALT and AST (defined as > or =30 U/L in men and > or =19 U/L in women) were calculated for alcohol and BMI separately and their joint exposure using logistic regression models.In multivariate logistic regression models adjusted for age, alcohol use, total cholesterol, serum triglycerides, fasting plasma glucose, systolic blood pressure, and diabetes mellitus, obesity independently increased the odds of elevated ALT in this cohort of older men and women by 3.0 (95% CI, 1.7-5.3) and 1.8 (95% CI, 1.1-2.7) respectively. Joint effects of consuming >3 alcoholic drinks/day and obesity raised the odds of elevated ALT by 8.9 (95% CI, 2.4-33.1) and AST by 21-fold (95% CI, 2.6-170.1), demonstrating synergism. Obese participants had higher odds of elevated ALT even at 0 < or = 1 drink/day.In older men and women, the combination of obesity with alcohol is synergistic in increasing the risk of liver injury.
