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Open Access Publications from the University of California

Scholarly Works (72 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2021)

Purpose

The association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults.

Methods

Participants included 5067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal probrain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality.

Results

The analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06).

Conclusions

Five CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.
    Cover page: Cardiovascular damage phenotypes and all-cause and CVD mortality in older adults
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2005)
    Survival following the onset of dementia has been reported to vary from 3 to over 9 years. We examined mortality in 3602 participants of the Cardiovascular Health (CHS) Cognition Study in four US communities evaluated for dementia incidence between 1992 and 1999 and followed for 6.5 years. By June 2000, 33 of 62 (53.2%) participants who developed vascular dementia (VaD) had died compared to 79 of 245 (32.2%) with Alzheimer's disease (AD), 66 of 151 (43.7%) with both AD and VaD, and 429 of 2318 (18.5%) with normal cognition. Using Cox proportional hazards regression with a time-dependent covariate for dementia status adjusted for age, gender and race, individuals with VaD were more than four times as likely to die during follow-up than those with normal cognition (HR: 4.4, 95% CI: 3.1-6.3). The hazard ratios were 2.1 (95% CI: 1.6-2.7) for AD and 2.5 (95% CI: 1.9-3.3) for both types. Adjusted accelerated life models estimated median survival from dementia onset to death as 3.9 years for those with VaD, 7.1 years for AD, 5.4 years for mixed dementia, and 11.0 years for matched controls with normal cognition. While persons with VaD died primarily from cerebrovascular disease, those with AD/mixed dementia died more frequently from dementia/failure to thrive.
      Cover page: Survival following dementia onset: Alzheimer's disease and vascular dementiaCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2014)

      Objectives

      To determine the association between interleukin-6 (IL-6), IL-6 soluble receptor (sR), and soluble tumor necrosis factor receptor-1 (sTNF-R1) and cognitive status in the oldest-old women.

      Design

      Twenty-year longitudinal cohort study.

      Setting

      Four clinical sites in the United States.

      Participants

      Women from the Study of Osteoporotic Fractures (N = 905; mean age 88.3 ± 2.8 at cognitive status adjudication).

      Measurements

      At Year 20, cognitive status was adjudicated as normal, mild cognitive impairment (MCI), or dementia. Inflammatory markers were measured from blood serum at Years 10 and 16 in a random sample of women.

      Results

      Over 10 years, 199 (22.0%) women developed MCI and 145 (16.0%) dementia. There were no significant associations between IL-6 or sTNF-R1 and cognitive status. High IL-6-sR (≥ 37,401.36 pg/mL, highest tertile) at Year 16 was significantly associated with lower risk of dementia (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.30-0.97) than in women with lower levels (<37,401.36 pg/mL, lower two tertiles). Women with high IL-6-sR at both time points (OR = 0.39, 95% CI = 0.17-0.89) or who transitioned to a high level (OR = 0.35, 95% CI = 0.14-0.88) had a lower risk of dementia.

      Conclusion

      In this cohort of white, high-functioning oldest-old women, a consistently high or an increasing level of IL-6-sR was associated with lower risk of dementia. Compared with other studies of younger-old adults, this suggests that the effect of inflammation on dementia may differ in younger-old and the oldest-old individuals. Understanding these differences will be crucial in interpreting results from ongoing clinical trials and in targeting therapeutic strategies to the oldest-old individuals.
        Cover page: Change in Inflammatory Markers and Cognitive Status in the Oldest‐Old Women from the Study of Osteoporotic Fractures
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2017)

        Background

        Previous research regarding anxiety as a predictor of future cognitive decline in older adults is limited and inconsistent. We examined the independent relationship between anxiety symptoms and subsequent cognitive decline.

        Methods

        We included 2,818 community-dwelling older men (mean age = 76.1, SD ±5.3 years) who were followed on an average for 3.4 years. We assessed anxiety symptoms at baseline using the Goldberg Anxiety Scale (GAS; range = 0-9). We assessed cognitive function at baseline and at two subsequent visits using the Modified Mini-Mental State Examination (3MS; global cognition) and the Trails B test (executive function).

        Results

        At baseline, there were 690 (24%) men with mild anxiety symptoms (GAS 1-4) and 226 (8%) men with moderate/severe symptoms (GAS 5-9). Men with anxiety symptoms were more likely to have depressed mood, poor sleep, more chronic medical conditions, and more impairment in activities of daily living compared to those with no anxiety symptoms. Compared to those with no anxiety symptoms at baseline, men with any anxiety symptoms were more likely to have substantial worsening in Trails B completion time (OR = 1.56, 95% CI 1.19, 2.05). The association was attenuated after adjusting for potential confounders, including depression and poor sleep, but remained significant (OR = 1.40, 95% CI 1.04, 1.88).

        Conclusion

        In cognitively healthy older men, mild anxiety symptoms may potentially predict future decline in executive functioning. Anxiety is likely a manifestation of an underlying neurodegenerative process rather than a cause.
          Cover page: Anxiety symptoms and risk of cognitive decline in older community-dwelling men
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2018)

          Objectives

          Research is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women.

          Method

          We conducted secondary analyses of data collected from 1425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment at baseline were excluded.

          Results

          At baseline, 190 (13%) women had moderate/severe anxiety symptoms and 403 (28%) had mild anxiety symptoms. Compared with those with no anxiety symptoms at baseline, women with mild anxiety symptoms were more likely to develop dementia at follow-up (multivariable-adjusted odds ratio = 1.66, 95% confidence interval 1.12-2.45). No significant association was observed between anxiety symptoms and MCI.

          Conclusion

          In the oldest old women, our findings suggest that mild anxiety symptoms may predict future risk of dementia, but not MCI. Future studies should explore potential biological mechanisms underlying associations of anxiety with cognitive impairment.
            Cover page: Anxiety symptoms and risk of dementia and mild cognitive impairment in the oldest old women
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2016)

            Objective

            To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.

            Methods

            In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.

            Results

            In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (β = -0.27, p < 0.001) and to higher WMH (β = 0.23, p = 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p = 0.043) in the mediation analyses.

            Conclusions

            Sustained exposure to high IL-6 over 10 years rather than the rate of change in IL-6 or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH.
              Cover page: Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2008)

              Hypertension is highly prevalent in elderly individuals and may be associated with cognitive decline, but the mechanisms by which hypertension may impact brain structure, and thereby modulate the time course of late-life cognitive performance, are not well understood. Therefore we used Localized Components Analysis, a novel computational method, to measure spatially-localized patterns of corpus callosum (CC) atrophy in 28 right-handed female subjects aged 75-79 years in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik), a large-scale epidemiological study of aging. Localized callosal atrophy in the posterior midbody and splenium was significantly associated with systolic blood pressure in linear statistical models that controlled for age, while associations between blood pressure and anterior CC atrophy measures were not statistically significant. Additionally, overall measures of global CC atrophy were not significantly associated with blood pressure. The posterior CC may be differentially vulnerable to hypertension-associated atrophy, possibly due to its relatively tenuous vascularization.

                Cover page: Localized measures of callosal atrophy are associated with late-life hypertension: AGES-Reykjavik Study.
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2003)

                Objective

                To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study.

                Design

                The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort.

                Setting

                Multicenter population study.

                Patients

                We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI.

                Main outcome measures

                The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type.

                Results

                The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%.

                Conclusions

                Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.
                  Cover page: Prevalence and Classification of Mild Cognitive Impairment in the Cardiovascular Health Study Cognition Study: Part 1Creative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2015)
                  The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over 80. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age = 87.4, 51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (min), and intensity (metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean ± SD/day: 1766 ± 1345 steps, 202 ± 311 kcal, 211 ± 39 min, 1.8 ± 1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted.
                    Cover page: Objective measures of physical activity, white matter integrity and cognitive status in adults over age 80
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2007)

                    Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.

                      Cover page: Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia.
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