Search

Introduction: The effect of APOE4 allele on dementia risk is well established in Alzheimer's disease and Parkinson's disease (PD). However, it is unknown if sex modifies this relationship. We sought to determine the effect of sex on the relationship between APOE4 status and incident cognitive decline in PD. Methods: Data from the prospectively collected longitudinal National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and Neuropathology Data Set (NDS) were analyzed. The NACC develops and maintains data from approximately 29 National Institutes of Aging-funded Alzheimer's Disease Research Centers. Further details may be found at the NACC web site (www.alz.washington.edu). The visit at which diagnosis of PD was made was termed the baseline visit. All patients with a PD diagnosis but without dementia at the baseline visit were included in the analyses. Results: Presence of APOE4 allele was associated with higher odds (OR = 7.4; P <.001) of subsequent diagnosis of dementia and with a faster time to developing dementia (P =.04). Those with APOE4 allele were more likely to have neuropathology associated with Alzheimer's disease than those without APOE4 allele. We did not find any difference by sex. There were no differences between Lewy body pathology or neuron loss in the substantia nigra between the 2 groups. Sex was not associated with dementia risk in PD (OR = 0.53, P =.15) or with the time to dementia onset (P =.22). Sex did not modify the relationship between the APOE4 allele and dementia onset in PD patients (P =.12) Conclusions: APOE4 allele status in PD may be a predictor of cognitive decline in PD but does not appear to be modified by sex. [ABSTRACT FROM AUTHOR]

Background: Given the detrimental impacts of visual and cognitive impairment separately, in older adults, understanding their coexistence could inform strategies against age-related cognitive changes.Methods: Participants from Washington County (White) and Jackson (Black) sites of the Atherosclerosis Risk in Communities Study were recruited who differed on racial, regional, urbanicity, and community-based factors. Presenting distance visual acuity (DVA; representing vision loss due to disease or lack of eye-care), corrected DVA (representing optimal correction for refractive loss of vision), and contrast sensitivity were measured. Factor scores for global cognition, memory, executive function, and language domains were calculated for 3 visits. We quantified the associations of vision measures with change in cognitive scores, stratified by community/race, using generalized estimating equations.Results: In 982 participants, mean (standard deviation [SD]) baseline age was 74 (4) years, with 37% males and 45% Jackson/Black participants. As hypothesized, after accounting for potential confounders, in the better-eye, worse presenting DVA was associated with greater 10-year decline rate in global cognition, memory, and executive function in Washington County/White participants (eg, global cognition: -0.08 SD [95% confidence interval: -0.12, -0.04]). Worse corrected DVA was associated with greater 10-year decline rate in executive function in Washington County/White participants (-0.10 SD [-0.15, -0.04]). Better contrast sensitivity was associated with lower 10-year decline rate in global cognition and executive function in Washington County/White participants (eg, global cognition: 0.10 SD [0.06,0.14]). None of these associations were confirmed in Jackson/Black participants.Conclusions: Our study supports a functional link between some vision measures and cognition in older adults, but in only 1 of the 2 communities studied. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are excellent tumor biomarkers because of their cell-type specificity and abundance. However, many miRNA detection methods, such as real-time PCR, obliterate valuable visuospatial information in tissue samples. To [...]

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]

PURPOSE: Methods for depth normalization have been assessed primarily with simulated data or cell-line–mixture data. There is a pressing need for benchmark data enabling a more realistic and objective assessment, especially in the context of small RNA sequencing. METHODS: We collected a unique pair of microRNA sequencing data sets for the same set of tumor samples; one data set was collected with and the other without uniform handling and balanced design. The former provided a benchmark for evaluating evidence of differential expression and the latter served as a test bed for normalization. Next, we developed a data perturbation algorithm to simulate additional data set pairs. Last, we assembled a set of computational tools to visualize and quantify the assessment. RESULTS: We validated the quality of the benchmark data and showed the need for normalization of the test data. For illustration, we applied the data and tools to assess the performance of 9 existing normalization methods. Among them, trimmed mean of M-values was a better scaling method, whereas the median and the upper quartiles were consistently the worst performers; one variation of remove unwanted variation had the best chance of capturing true positives but at the cost of increased false positives. In general, these methods were, at best, moderately helpful when the level of differential expression was extensive and asymmetric. CONCLUSION: Our study (1) provides the much-needed benchmark data and computational tools for assessing depth normalization, (2) shows the dependence of normalization performance on the underlying pattern of differential expression, and (3) calls for continued research efforts to develop more effective normalization methods. [ABSTRACT FROM AUTHOR]

Background/Aim To identify changes in endothelial cell density (ECD) and central corneal thickness (CCT) in eyes undergoing femtosecond laser-assisted cataract surgery (FLACS) compared with conventional phacoemulsification surgery (CPS). Methods This is an intraindividual randomised, controlled clinical trial. One eye was randomised to receive FLACS, while the contralateral eye of the same patient received CPS. The femtosecond laser pretreatment included creating main and side-port corneal incisions, capsulotomy and lens fragmentation. Non-contact endothelial cell microscopy and pachymetry were performed preoperatively and at postoperative day 1, week 1, month 1 and month 3. results A total of 134 paired eyes from 67 patients were included in the analysis. ECD was not significantly different between the two groups at either postoperative month 1 (2370±580 cells/mm² and 2467±564 cells/mm² in FLACS and CPS groups, respectively; p=0.18) or at postoperative month 3 (2374±527 cells/mm² and 2433±526 cells/mm² in FLACS and CPS groups, respectively; p=0.19). No significant difference was observed in the mean CCT values between the two groups over the follow-up period (p>0.05). Conclusion Postoperative corneal ECD and CCT were comparable between FLACS and CPS during the 3 months' follow-up period. [ABSTRACT FROM AUTHOR]

Background: Babesia, a tick-borne genus of intraerythrocytic parasites, is understudied in humans outside of established high-endemic areas. There is a paucity of data on Babesia in Africa, despite evidence that it is regionally present. A pilot study suggested that Babesia was present in a rural district of Tanzania. Methodology/Principal findings: A cross-sectional study was conducted July-August 2017: residents in a case hamlet that had clustering of subjects with high signal-to-cut off (S/CO) ratios for antibodies against B. microti in the pilot study, and a control hamlet that had lacked significant signal, were evaluated for B. microti. Subjects aged ≥15yrs (n = 299) underwent clinical evaluation and household inspections; 10ml whole blood was drawn for Babesia transcription mediated amplification (TMA), B. microti indirect fluorescent antibody testing (IFA) and rapid diagnostic testing (RDT) for Plasmodium spp. Subjects aged <15yrs (n = 266) underwent a RDT for Plasmodium and assessment by ELISA for B. microti antibodies. A total of 570 subjects participated (mean age 22 [<1 to 90yrs]) of whom 50.7% were female and 145 (25.5%) subjects were Plasmodium RDT positive (+). In those <15yrs, the median ELISA S/CO was 1.11 (IQR 0.80–1.48); the median S/CO in the case (n = 120) and control (n = 146) hamlets was 1.19 (IQR 0.81–1.48) and 1.06 (IQR 0.80–1.50) respectively (p = 0.4). Children ≥5yrs old were more likely to have a higher S/CO ratio than those <5yrs old (p<0.001). One hundred (38%) subjects <15yrs were Plasmodium RDT+. The median S/CO ratio (children <15yrs) did not differ by RDT status (p = 0.15). In subjects ≥15yrs, no molecular test was positive for Babesia, but four subjects (1.4%) were IFA reactive (two each at titers of 128 and 256). Conclusions/Significance: The findings offer further support for Babesia in rural Tanzania. However, low prevalence of seroreactivity questions its clinical significance. [ABSTRACT FROM AUTHOR]