Midlife cumulative deficit frailty predicts Alzheimer's disease-related plasma biomarkers in older adults.

BACKGROUND: The study explores whether frailty at midlife predicts mortality and levels of biomarkers associated with Alzheimer's disease and related dementias (ADRD) and neurodegeneration by early old age. We also examine the heritability of frailty across this age period. METHODS: Participants were 1,286 community-dwelling men from the Vietnam Era Twin Study of Aging at average ages 56, 62 and 68, all without ADRD at baseline. The cumulative deficit frailty index (FI) comprised 37 items assessing multiple physiological systems. Plasma biomarkers at age 68 included beta-amyloid (Aß40, Aß42), total tau (t-tau) and neurofilament light chain (NfL). RESULTS: Being frail doubled the risk of all-cause mortality by age 68 (OR = 2.44). Age 56 FI significantly predicted age 68 NfL (P = 0.014), Aß40 (P = 0.001) and Aß42 (P = 0.023), but not t-tau. Age 62 FI predicted all biomarkers at age 68: NfL (P = 0.023), Aß40 (P = 0.002), Aß42 (P = 0.001) and t-tau (P = 0.001). Age 68 FI scores were associated with age 68 levels of NfL (P = 0.027), Aß40 (P < 0.001), Aß42 (P = 0.001) and t-tau (P = 0.003). Genetic influences accounted for 45-48% of the variance in frailty and significantly contributed to its stability across 11 years. CONCLUSIONS: Frailty during one's 50s doubled the risk of mortality by age 68. A mechanism linking frailty and ADRD may be through its associations with biomarkers related to neurodegeneration. Cumulative deficit frailty increases with age but remains moderately heritable across the age range studied. With environmental factors accounting for about half of its variance, early interventions aimed at reducing frailty may help to reduce risk for ADRD.

Rostral-middle locus coeruleus integrity and subjective cognitive decline in early old age.

OBJECTIVES: Abnormal tau, a hallmark Alzheimer's disease (AD) pathology, may appear in the locus coeruleus (LC) decades before AD symptom onset. Reports of subjective cognitive decline are also often present prior to formal diagnosis. Yet, the relationship between LC structural integrity and subjective cognitive decline has remained unexplored. Here, we aimed to explore these potential associations. METHODS: We examined 381 community-dwelling men (mean age = 67.58; SD = 2.62) in the Vietnam Era Twin Study of Aging who underwent LC-sensitive magnetic resonance imaging and completed the Everyday Cognition scale to measure subjective cognitive decline along with their selected informants. Mixed models examined the associations between rostral-middle and caudal LC integrity and subjective cognitive decline after adjusting for depressive symptoms, physical morbidities, and family. Models also adjusted for current objective cognitive performance and objective cognitive decline to explore attenuation. RESULTS: For participant ratings, lower rostral-middle LC contrast to noise ratio (LCCNR) was associated with significantly greater subjective decline in memory, executive function, and visuospatial abilities. For informant ratings, lower rostral-middle LCCNR was associated with significantly greater subjective decline in memory only. Associations remained after adjusting for current objective cognition and objective cognitive decline in respective domains. CONCLUSIONS: Lower rostral-middle LC integrity is associated with greater subjective cognitive decline. Although not explained by objective cognitive performance, such a relationship may explain increased AD risk in people with subjective cognitive decline as the LC is an important neural substrate important for higher order cognitive processing, attention, and arousal and one of the first sites of AD pathology.

Harmonisation of read-across methodology for drug substance extractables and leachables (E&Ls).

Health-based exposure limits (HBELs) are derived for leachables from polymeric components that interact with the drug substance which exceed a safety concern threshold (SCT). However, given the nature of leachables, there is not always chemical-specific toxicology data. Read-across methodology specific to extractables and leachables (E&Ls) was developed based on survey data collected from 11 pharmaceutical companies and methodology used in other industries. One additional challenge for E&L read-across is most toxicology data is from the oral route of administration, whereas the parenteral route is very common for the leachable HBEL derivation. A conservative framework was developed to estimate oral bioavailability and the corresponding oral to parenteral extrapolation factor using physical chemical data. When this conservative framework was tested against 73 compounds with oral bioavailability data, it was found that the predicted bioavailability based on physico-chemical properties was conservatively greater than or equal to the experimental bioavailability 79% of the time. In conclusion, an E&L read-across methodology has been developed to provide a consistent, health protective framework for deriving HBELs when toxicology data is limited.

Severity and correlates of brain fog in people with traumatic brain injury.

Brain fog is one symptom that has been underexplored in traumatic brain injury (TBI). We explored the cognitive and affective correlates of brain fog in people with symptomatic mild TBI (n = 15), moderate-to-severe TBI (n = 15), and a healthy control group (n = 16). Measures across the studies assessed "brain fog" (Mental Clutter Scale), objective cognition (Useful Field of View® and Cogstate Brief Battery®), post-concussive symptoms (Post-Concussion Symptom Scale), and depressive symptoms (Profile of Moods Scale). Brain fog was higher in symptomatic mild TBI and moderate-to-severe TBI compared with healthy controls. Greater brain fog corresponded to greater depressive symptoms in symptomatic mild TBI. Greater brain fog corresponded to poorer episodic memory and working memory in moderate-to-severe TBI. Brain fog appears to reflect challenges in recovery, including depressive symptoms and worse cognitive function. Screening for brain fog might be worthwhile in people with brain injuries.

The Role of Cognitive Self-Report Measure Type in Predicting Cognitive Decline Among Older Adults: A Systematic Review.

Many types of items are used to measure self-reported cognition, resulting in heterogeneity across studies. Certain cognitive self-report measure types may be more predictive of future decline. Therefore, the purpose of this systematic review was to compare whether specific types of cognitive self-report measures better predict risk for cognitive decline over time when measures are directly compared within the same study. The PRISMA criteria guided the review. Eligibility criteria included: longitudinal studies, outcome of cognitive decline, at least 2 different cognitive self-report measures, and no cognitive impairment at baseline. Nineteen studies were included in the final review. A narrative synthesis of results was completed, resulting in 3 thematic groups of comparisons across self-reported measure types. Self-reported memory decline with worry and peer perceptions of memory were associated with the highest risk for cognitive decline. Future longitudinal investigations of self-reported cognitive problems should focus on using measures that may be most sensitive to predicting cognitive decline risk.

Downsampled depth encoding for enhanced 3D range geometry compression.

The use of three-dimensional (3D) range geometry is expanding across a variety of disciplines ranging from medicine to the visual arts. A large amount of information is available in 3D range geometry, causing some applications to be limited in their ability to effectively store or transmit captured data. To help alleviate this constraint, a variety of 3D range data compression techniques have been proposed. One method, multiwavelength depth (MWD) encoding, smoothly encodes 3D range geometry into the three color channels of a 2D RGB image. To the best of our knowledge, we present a novel compression enhancement to further reduce file sizes that employs image downsampling, MWD encoding, and lossless (e.g., PNG) or lossy (e.g., JPEG) compression. Image upsampling is used to return downsampled encodings to their original resolution from which the 3D information is then decoded. The proposed method is robust to various scales of downsampling and levels of lossy compression. For example, when this method was applied with 50% downsampling and JPEG 85 to an encoding of a 3D face scan, a compression ratio of 68.85:1 versus the raw data was achieved with a global RMS reconstruction accuracy of 98.77%. Experimental results demonstrate that the proposed method can provide substantial file size savings at minimal reduction in overall reconstruction accuracy.

Foveated 3D range geometry compression via loss-tolerant variable precision depth encoding.

The capacity of three-dimensional (3D) range geometry acquisition methods to capture high-precision scans at high frame rates increases every year. These improvements have influenced a broadening range of disciplines to implement 3D range geometry capture systems, including telepresence, medicine, the visual arts, and many others. However, its increased popularity, precision, and capture rates have caused mounting pressure on the storage and transmission of 3D range geometry, thus straining their capacities. Compression techniques seek to alleviate this pressure by offering reduced file sizes, while maintaining the levels of precision needed for particular applications. Several such compression methods use sinusoidal modulation approaches to encode floating-point 3D data into conventional 2D red, green, and blue (RGB) images. In some applications, such as telepresence, high precision may only be required in a particular region within a depth scan, thus allowing less important data to be compressed more aggressively. This paper proposes a feature-driven compression method that provides a way to encode regions of interest at higher levels of precision while encoding the remaining data less precisely to reduce file sizes. This method supports both lossless and lossy compression, enabling even greater file-size savings. For example, in the case of a depth scan of a bust, an algorithmically extracted bounding box of the face was used to create a foveated encoding distribution so that the facial region was encoded at higher precisions. When using JPEG 80, the RMS reconstruction error of this novel, to the best of our knowledge, encoding was 0.56 mm in the region of interest, compared to a globally fixed higher precision encoding where the error was 0.54 mm in the same region. However, the proposed encoding achieved a 26% reduction in overall compressed file size compared to the fixed, higher-precision encoding.

Parental dementia and subjective memory impairment in the health and retirement study.

OBJECTIVES: To examine relationships between subjective memory impairment (SMI) and parental dementia among in older adults while considering the interactive influence of depressive symptoms, ethnicity, and race. METHOD: The sample was drawn from the Health and Retirement Study, a nationally representative longitudinal study of aging (n = 3,809; Mage = 66.09; SD = 1.88; 84.20% White; 12.23% Black; 7.88% Hispanic). Biennial assessments included two measures of SMI (current memory problems and perceived memory decline), depressive symptoms, and parental dementia, over periods of up to sixteen years. Multilevel modeling analyses examined longitudinal relationships between parental dementia and SMI and whether depressive symptoms, ethnicity, and race interactively influenced this association. RESULTS: Results showed that when older adults reported parental dementia, they were more likely to report a decline in memory in the past two years. They also reported poorer current memory problems, especially when they experienced increased depressive symptoms. Associations of parental dementia were consistent across ethnicity and race. CONCLUSIONS: Results demonstrate the importance of considering parental dementia as a factor that may contribute to SMI in older adults.

HoloKinect: Holographic 3D Video Conferencing.

Recent world events have caused a dramatic rise in the use of video conferencing solutions such as Zoom and FaceTime. Although 3D capture and display technologies are becoming common in consumer products (e.g., Apple iPhone TrueDepth sensors, Microsoft Kinect devices, and Meta Quest VR headsets), 3D telecommunication has not yet seen any appreciable adoption. Researchers have made great progress in developing advanced 3D telepresence systems, but often with burdensome hardware and network requirements. In this work, we present HoloKinect, an open-source, user-friendly, and GPU-accelerated platform for enabling live, two-way 3D video conferencing on commodity hardware and a standard broadband internet connection. A Microsoft Azure Kinect serves as the capture device and a Looking Glass Portrait multiscopically displays the final reconstructed 3D mesh for a hologram-like effect. HoloKinect packs color and depth information into a single video stream, leveraging multiwavelength depth (MWD) encoding to store depth maps in standard RGB video frames. The video stream is compressed with highly optimized and hardware-accelerated video codecs such as H.264. A search of the depth and video encoding parameter space was performed to analyze the quantitative and qualitative losses resulting from HoloKinect's lossy compression scheme. Visual results were acceptable at all tested bitrates (3-30 Mbps), while the best results were achieved with higher video bitrates and full 4:4:4 chroma sampling. RMSE values of the recovered depth measurements were low across all settings permutations.

The Factor Structure of Items Assessing Subjective Memory: Between-Persons and Within-Persons across Time.

INTRODUCTION: Current understanding of the psychometric properties of items intended to assess the multidimensional construct of subjective memory (SM) is limited, as longitudinal studies of aging commonly use single items or brief sets of items to assess SM. Investigating how SM items cluster within individuals over time would increase the understanding of how combining these items impacts their utility as an early indicator of cognitive change in the aging trajectory. To address this need, the current study examined the factor structure of a brief set of SM items in an existing longitudinal study focused on cognitive aging at both the within-person and between-person levels. METHODS: Data were drawn from the Einstein Aging Study, a longitudinal cohort study of aging (N = 1,239, Mage = 77.51, SD = 5.03; 69.50% white; 24.27% black; 6.23% other). Community-dwelling older adults from an urban area of New York City were interviewed annually. At each wave, participants responded to 6 items intended to assess SM. Items assessed participants' perceived memory decline as well as current memory ability. Multilevel exploratory factor analyses examined which factor solution best fit the data at between-person and within-person levels. RESULTS: Factor structure of the SM items varied at the two levels. At the within-person level, two factors emerged, whereas at the between-person level, a single factor best represented the SM items. Items assessing perceived declines in memory functioning tended to have similar trajectories, while items assessing current memory ability were less related to change over time. CONCLUSION: Items appeared to assess two different dimensions of SM when examining within-person changes in SM across time; however, the item structure suggested no other items covaried systematically within persons over time. In contrast to the conceptualization of SM as a multidimensional construct, our findings suggest that when measuring SM between individuals, SM items tend to capture a single dimension underlying SM. This may be due to the long retrospection period of items assessing perceived memory ability. A single item assessing perceived memory decline in older adults without evidence of objective cognitive impairment may be sufficient to monitor memory change in clinical or research settings.

Longitudinal relationships among depressive symptoms and three types of memory self-report in cognitively intact older adults.

OBJECTIVES: The current study examined whether self-reported memory problems among cognitively intact older adults changed concurrently with, preceded, or followed depressive symptoms over time. DESIGN: Data were collected annually via in-person comprehensive medical and neuropsychological examinations as part of the Einstein Aging Study. SETTING: Community-dwelling older adults in an urban, multi-ethnic area of New York City were interviewed. PARTICIPANTS: The current study included a total of 1,162 older adults (Mage = 77.65, SD = 5.03, 63.39% female; 74.12% White). Data were utilized from up to 11 annual waves per participant. MEASUREMENTS: Multilevel modeling tested concurrent and lagged associations between three types of memory self-report (frequency of memory problems, perceived one-year decline, and perceived ten-year decline) and depressive symptoms. RESULTS: Results showed that self-reported frequency of memory problems covaried with depressive symptoms only in participants who were older at baseline. Changes in perceived one-year and ten-year memory decline were related to changes in depressive symptoms across all ages. Depressive symptoms increased the likelihood of perceived ten-year memory decline the next year; however, perceived ten-year memory decline did not predict future depressive symptoms. Additionally, no significant temporal relationship was observed between depressive symptoms and self-reported frequency of memory problems or perceived one-year memory decline. CONCLUSION: Our findings highlight the importance of testing the unique associations of different types of self-reported memory problems with depressive symptoms.

Variable precision depth encoding for 3D range geometry compression.

State-of-the-art 3D range geometry compression algorithms that utilize principles of phase shifting perform encoding with a fixed frequency; therefore, it is not possible to encode individual points within a scene at various degrees of precision. This paper presents a novel, to the best of our knowledge, method for accurately encoding 3D range geometry within the color channels of a 2D RGB image that allows the encoding frequency-and therefore the encoding precision-to be uniquely determined for each coordinate. The proposed method can thus be used to balance between encoding precision and file size by encoding geometry along a statistical distribution. For example, a normal distribution allows for more precise encoding where the density of data is high and less precise encoding where the density of data is low. Alternative distributions may be followed to produce encodings optimized for specific applications. In general, the nature of the proposed encoding method enables the precision to be freely controlled at each point or centered around identified features of interest, ideally enabling this method to be used within a wide range of applications.

Memory complaints and depressive symptoms over time: a construct-level replication analysis.

BACKGROUND: Memory complaints and depressive symptoms are frequently associated in older adults and both serve as potential indicators of future cognitive decline. However, the temporal ordering of the development of these two symptoms remains unclear. The goal of the current study was to examine concurrent and temporal relationships between memory complaints and depressive symptoms in older adults. METHODS: Data were drawn from two longitudinal, nationally representative datasets and included cognitively intact older adults aged 65 and over. The datasets in the current study were from the National Health and Aging Trends Study (NHATS) and the Health and Retirement Study (HRS). Using an integrative analytic framework, we tested bidirectional temporal relationships between memory complaints (memory ratings and perceived memory decline) and depressive symptoms over 6 to 9 years of data in over 5000 older adults across these two samples. RESULTS: Across both datasets, perceived memory decline predicted future depressive symptoms whereas memory ratings did not. Additionally, results showed that at times when depressive symptoms tended to be higher, memory complaints were also higher, but depressive symptoms did not predict future memory complaints. One finding that was inconsistent across datasets was memory ratings predicting depressive symptoms. After accounting for covariates, this relationship was only significant in one dataset. CONCLUSIONS: Cognitively intact older adults who report memory decline may be at risk for developing depressive symptoms in the future. Furthermore, our findings highlight the importance of using immediate replication of results across datasets to determine the generalizability of conclusions.

Lifting cognition: a meta-analysis of effects of resistance exercise on cognition.

The health benefits of resistance exercises are well established; however, the effects of resistance training on cognition are not as well understood. The purpose of this meta-analysis was to evaluate the evidence of resistance exercise's effects on cognition. A systematic search identified 24 studies that were included in the analyses. These articles ranged in the protocols utilized and in how they studied the effects of resistance training on cognition. Four primary analyses were carried out to assess the effects of resistance exercise on cognitive outcomes: (1) composite cognitive scores, (2) screening measures of cognitive impairment, (3) measures of executive functions, and (4) measures of working memory. Results revealed positive effects of resistance training on composite cognitive scores (SMD 0.71, 95% CI 0.30-1.12), screening measures of cognitive impairment (SMD 1.28, 95% CI 0.39-2.18), and executive functions (SMD 0.39, 95% CI 0.04-0.74), but no effect on measures of working memory (SMD 0.151, 95% CI - 0.21 to 0.51). High heterogeneity was observed in all analyses. Resistance training appears to have positive effects on cognition; however, future research will need to determine why the effects are so variable.

Personality determinants of subjective executive function in older adults.

Objectives: Problems in subjective executive function, the perceived cognitive control of mental processes for goal-directed behavior, may indicate cognitive impairment in older adulthood. Although, previous studies highlight the importance of personality on objective cognitive performance, no studies clarify their role with subjective executive function. To inform methods of early identification of cognitive impairment, this study explored how temperament and personality traits account for problems in subjective executive function.Method: The current project examined the associations between temperament and personality on subjective executive function across two samples of community-dwelling older adults (65+ years, n1 = 25, n2 = 50). Both studies measured subjective executive function (Behavioral Rating Inventory of Executive Function-Adult) and separately administered scales on temperament (Adult Temperament Questionnaire) and personality (Big Five Inventory).Results: Concerning temperament, older adults higher in negative affect endorsed greater difficulty in subjective executive function. Regarding personality traits, older adults with higher neuroticism and lower conscientiousness reported higher difficulty in subjective executive function.Conclusion: Findings enhance our understanding of subtle cognitive changes and may aid in early detection. In particular, distressful inclinations were associated with more reported problems in executive function whereas problem-solving tendencies were inversely related. Future work should examine if enhanced negativity coupled with analytical disengagement predicts problems in subjective executive function over time.

Conservation of resources and suicide proneness after oilrig disaster.

The current study applied the Conservation of Resources (COR) disaster theory to explain suicide proneness after the Deepwater Horizon oilrig explosion. We had 213 residents in affected areas with complete measures of resource stability, distress, and coping 18 months after the disaster. Overall, 10% expressed clinically elevated suicide proneness. The COR model had excellent fit that accounted for 41% of inter-individual differences in suicide proneness. Aligned with theory, residents lacking resources who experienced distress and coped by avoidance were more suicide-prone. Fostering resource stability and constructive coping after catastrophe may help reduce suicide proneness and prevent suicide in disaster-impacted citizens.

Predicting current and future anxiety symptoms in cognitively intact older adults with memory complaints.

OBJECTIVES: Memory complaints are a common concern for older adults and may co-occur with anxiety symptoms. Although both memory complaints and anxiety are associated with heightened cognitive decline risk, little is known about how these symptoms develop over time. The purpose of this study was to examine the differential concurrent and longitudinal relationships among anxiety symptoms and two types of memory complaints in cognitively intact older adults. METHODS/DESIGN: The current study sample was drawn from two longitudinal, nationally representative datasets, the National Health and Aging Trends Study (NHATS) and the Health and Retirement Study (HRS). Cognitively intact older adults aged 65 and over were included, representing six (n = 5069; NHATS) and two (n = 5284; HRS) waves of data, respectively. Using multilevel linear modeling, we tested bidirectional relationships between anxiety and two types of memory complaints: current rating of memory performance and perceived memory decline. RESULTS: Concurrent associations between anxiety symptoms and memory complaints were found in both datasets: At times when current memory performance was rated more poorly or perceived memory decline was reported, anxiety symptoms tended to be higher, and vice versa. A longitudinal relationship was identified in NHATS such that perceived memory decline, and not current memory rating, predicted future anxiety symptoms. CONCLUSION: This study provides a better understanding of the relationships between memory complaints and anxiety symptoms over time. Cognitively intact older adults with perceived memory decline are at greater risk for current as well as future anxiety symptoms.

Two-channel depth encoding for 3D range geometry compression.

This paper presents a novel method for accurately encoding 3D range geometry within only two channels of a 2D RGB image using a two-frequency phase-shifting approach. Once encoded within a 2D image, 3D geometry can be further compressed with conventional lossless or lossy image compression methods. The nature of the proposed two-channel encoding is relatively smooth; thus, large compression ratios with high reconstruction accuracies can be achieved and are experimentally demonstrated. For example, a compression ratio of 2883:1 was achieved, compared with the STL format, with a reconstruction RMS error of 0.45 mm (99.8% accuracy) when JPEG 85 was used with the proposed method. This paper also demonstrates how a 24-bit color texture map can be encoded alongside 3D geometry within a single 2D image.

Environmental and Sensor Integration Influences on Temperature Measurements by Rotary-Wing Unmanned Aircraft Systems.

Obtaining thermodynamic measurements using rotary-wing unmanned aircraft systems (rwUAS) requires several considerations for mitigating biases from the aircraft and its environment. In this study, we focus on how the method of temperature sensor integration can impact the quality of its measurements. To minimize non-environmental heat sources and prevent any contamination coming from the rwUAS body, two configurations with different sensor placements are proposed for comparison. The first configuration consists of a custom quadcopter with temperature and humidity sensors placed below the propellers for aspiration. The second configuration incorporates the same quadcopter design with sensors instead shielded inside of an L-duct and aspirated by a ducted fan. Additionally, an autopilot algorithm was developed for these platforms to face them into the wind during flight for kinematic wind estimations. This study will utilize in situ rwUAS observations validated against tower-mounted reference instruments to examine how measurements are influenced both by the different configurations as well as the ambient environment. Results indicate that both methods of integration are valid but the below-propeller configuration is more susceptible to errors from solar radiation and heat from the body of the rwUAS.

Moving towards a Network of Autonomous UAS Atmospheric Profiling Stations for Observations in the Earth's Lower Atmosphere: The 3D Mesonet Concept.

The deployment of small unmanned aircraft systems (UAS) to collect routine in situ vertical profiles of the thermodynamic and kinematic state of the atmosphere in conjunction with other weather observations could significantly improve weather forecasting skill and resolution. High-resolution vertical measurements of pressure, temperature, humidity, wind speed and wind direction are critical to the understanding of atmospheric boundary layer processes integral to air-surface (land, ocean and sea ice) exchanges of energy, momentum, and moisture; how these are affected by climate variability; and how they impact weather forecasts and air quality simulations. We explore the potential value of collecting coordinated atmospheric profiles at fixed surface observing sites at designated times using instrumented UAS. We refer to such a network of autonomous weather UAS designed for atmospheric profiling and capable of operating in most weather conditions as a 3D Mesonet. We outline some of the fundamental and high-impact science questions and sampling needs driving the development of the 3D Mesonet and offer an overview of the general concept of operations. Preliminary measurements from profiling UAS are presented and we discuss how measurements from an operational network could be realized to better characterize the atmospheric boundary layer, improve weather forecasts, and help to identify threats of severe weather.