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Introduction: Accumulated vascular damage contributes to the onset and progression of vascular dementia and possibly to Alzheimer's disease. Here we evaluate the feasibility and utility of using retinal imaging of microvascular markers to identify older adults at risk of cognitive disease. Methods: The "Eye Determinants of Cognition" (EyeDOC) study recruited a biracial, population‐based sample of participants from two sites: Jackson, MS, and Washington Co, MD. Optical coherence tomographic angiography (OCTA) was used to capture vessel density (VD) from a 6 × 6 mm scan of the macula in several vascular layers from 2017 to 2019. The foveal avascular zone (FAZ) area was also estimated. Image quality was assessed by trained graders at a reading center. A neurocognitive battery of 10 tests was administered at three time points from 2011 to 2019 and incident mild cognitive impairement (MCI)/dementia cases were ascertained. Linear mixed‐effects models were used to evaluate associations of retinal vascular markers with cognitive factor score change over time. Results: Nine‐hundred and seventy‐six older adults (mean age of 78.7 (± 4.4) years, 44% black) were imaged. Gradable images were obtained in 55% (535/976), with low signal strength (66%) and motion artifact (22%) being the largest contributors to poor quality. Among the 297 participants with both high‐quality images and no clinically significant retinal pathology, the average decline in global cognitive function factor score was −0.03 standard deviations per year. In adjusted analyses, no associations of VD or FAZ with longitudinal changes in either global cognitive function or with incident MCI/dementia were found. Conclusions: In this large biracial community sample of older adults representative of the target population for retinal screening of cognitive risk, we found that obtaining high‐quality OCTA scans was infeasible in a nearly half of older adults. Among the select sample of healthier older adults with scans, OCTA markers were not predictive of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. Design: Prospective cohort study. Setting: Hospital‐based enrollment. Participants: People with glaucoma or suspected glaucoma. Measurements: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow‐up calls. Study participants were categorized into three groups–fallers with injurious consequences, fallers without injurious consequences, and non‐fallers based on fall status in the first year. Physical activity was assessed by waist‐bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The 3‐year longitudinal changes of physical activity and FoF were modeled using mixed‐effects models. Results: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (−425 steps/d, 95% confidence interval (CI) = −793, −57), daily active minutes (−13 min/d, 95% CI = −21, −6), and daily moderate and vigorous physical activity (MVPA) minutes (−3 MVPA minutes/d, 95% CI = −5, 0) over the 3‐year period as compared to non‐fallers; however, physical activity did not significantly decline among non‐injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non‐injurious fallers when compared to non‐fallers. Conclusion: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a 3‐year period, while minimal changes were observed in FoF. [ABSTRACT FROM AUTHOR]

OBJECTIVE Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. DESIGN Prospective observational cohort study. SETTING Hospital‐based single‐center recruitment. PARTICIPANTS Individuals with glaucoma or suspected glaucoma. MEASUREMENTS FoF was measured annually over a 3‐year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch‐analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3‐year period using monthly mail‐in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within‐participant changes in fall rates and physical activity across study years. RESULTS: At lower FoF levels (FoF≤0), each one‐unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95% confidence interval [CI] = 1.55‐4.81) but was not associated with average daily steps (P =.44). Similar results were seen when fall rates were normalized by number of steps taken (P =.97). At higher FoF levels (FoF > 0), inter‐year changes in FoF scores were not significantly associated with reporting a fall in the following year (P =.78) but were associated with 407 fewer average daily steps per one‐unit change in FoF (95% CI = −743 to −71). CONCLUSION: FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847‐1851, 2020. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether visual field (VF) damage or other factors confer a similar risk of falling when falls are ascertained as a rate over time (falls/year) as when ascertained over activity (falls/step). Design: Prospective, observational cohort study. Setting: Clinic‐based recruitment with real‐world monitoring of falls and physical activity. Particpants: Individuals with glaucoma or suspected glaucoma (N=230). Measurements: Participants recorded falls using daily calendars, with injuries identified in a follow‐up questionnaire. Annual 1‐week accelerometer trials were used to estimate steps. VF results from both eyes were merged to determine integrated VF sensitivity, with lower sensitivity indicating greater VF damage. Other potential risk factors for falls (age, sex, race, comorbid illness, polypharmacy) were determined using questionnaires. Results: The cumulative probability of falls was 45.2% at 12 months and 61.6% at 24 months; cumulative probability of injurious falls was 23.3% at 12 months and 40.0% at 24 months. Greater VF damage was associated with higher rates of falls/steps (incident rate ratio = 1.40/5 dB decrement in sensitivity; p =.004) but not with more falls/year (incident rate ratio = 1.25/5 dB decrement in sensitivity; p =.07). Several additional variables (older age, female sex, more comorbid disease) were also associated with a higher rate of falls/step (p <.02 for all) but not with falls/year (p > 0.10). Black participants had fewer falls/year than whites (p =.002) but did not differ in falls/step (p =.07). Similar results were obtained when injurious falls were analyzed. Conclusions: Risk factors associated with frequent falls when walking (falls/step) are not properly identified when analyzing falls as a rate over time (falls/year). Given the clinical importance of preventing falls while preserving physical activity, falls assessment integrated with activity measurement is recommended when determining whether a risk factor is associated with falls. J Am Geriatr Soc 67:87–92, 2019. [ABSTRACT FROM AUTHOR]

Upregulation of haptoglobin (Hp) expression in the rat during the acute phase (AP) response is the result of synergistic effects of IL-6–, IL-1β–, and corticosterone-activated signaling pathways. IL-6 signaling terminates in cis–trans interactions of the Hp gene hormone-responsive element (HRE) with transcription factors STAT3 and C/EBPβ. The aim of this study was to examine the unresolved molecular mechanism of glucocorticoid action. A 3-fold rise in serum corticosterone at 2 and 4 h of the AP response induced by turpentine administration preceded a 2.3-fold increase in the rate of Hp gene transcription at 12 h that was accompanied by a 4.8-fold increase in glucocorticoid receptor (GR), the appearance of an 86-kDa STAT3 isoform and 3.9-, 1.9-, and 1.7-fold increased amounts of 91-kDa STAT3, 35- and 42-kDa C/EBPβ isoforms in the nucleus. These events resulted in 4.6- and 2.5-fold increased Hp levels in the liver and serum at 24 h. HRE affinity chromatography and immunoblot analysis revealed that maximal occupancy of the HRE with GR, STAT3, and C/EBPβ at 12 h correlated with increased transcriptional activity of the Hp gene. Coimmunoprecipitation experiments showed that activated GR established de novo interaction with STAT3 isoforms while GR–C/EBPβ interactions observed during basal transcription increased during the AP response. Computer analysis of the HRE disclosed two potential GR-binding sites: one overlapping STAT3, another adjacent to a C/EBPβ-binding site. This finding and the experimental results suggest that activated GR through direct interactions with STAT3 and C/EBPβ, participates in Hp gene upregulation as a transcriptional coactivator. © 2010 IUBMB IUBMB Life, 62(2): 227–236, 2010 [ABSTRACT FROM AUTHOR]