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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network

Abstract Objective To investigate whether herpes simplex virus type 1 (HSV‐1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). Methods Among two subsets of the DIAN cohort (age range 19.6–66.6 years; median follow‐up 3.0 years) we examined (i) rate of cognitive decline ( N = 164) using change in mini‐mental state examination (MMSE) score, (ii) rate of whole brain atrophy ( N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV‐1 antibodies were assayed in baseline sera collected from 2009–2015. Linear mixed‐effects models were used to compare outcomes by HSV‐1 seropositivity and high HSV‐1 IgG titres/IgM status. Results There was no association between baseline HSV‐1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV‐1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope − 0.365, 95% CI: −0.958 to −0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV‐1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV‐1 seronegative. Among mutation‐negative individuals, no differences were seen by HSV‐1. Stratifying by APOE4 status yielded inconsistent results. Interpretation We found no evidence for a major role of HSV‐1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early‐onset AD.

Warren‐Gash, Charlotte↗
DOE OSTI2021

Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging

Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 ( 18 F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, setting, and participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [ 18 F]Flortaucipir PET in the discovery cohort (n = 1135) or [ 18 F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main outcomes and measures: Baseline [ 18 F]flortaucipir/[ 18 F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [ 18 F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R 2 , 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aβ-positive CU group (R 2 , 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [ 18 F]RO948 PET cohort. MRI mediated the association between [ 18 F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [ 18 F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2009

Parathyroid Hormone Levels and Cognition

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

Burnett, J.↗
NASA NTRSDate not supplied

Considerations for Health and Performance During Surface Extravehicular Activities

BACKGROUND: NASA’s objectives for expanding human presence beyond low Earth orbit will require Extravehicular Activities (EVAs) on lunar and planetary surfaces. Given the physiological and functional demands of conducting surface EVAs in a pressurized spacesuit in reduced gravity environments, there is a possibility that crew injury and compromised physiological and/or functional performance may present. OVERVIEW: Many human health and performance knowledge gaps exist in regards to exploration EVA that require characterization to ensure safety, reliability, and mission success. To address knowledge gaps, EVA simulations in Earth-based analog environments and/or spacesuit simulators can be utilized to provide valuable insights into task-based physiologic and metabolic costs, cognitive loads, and associated operational limitations to inform future mission concepts. Physical workloads approaching 60% of maximum metabolic rates and 85% age-predicted heart rate maxima; core body temperatures approaching 100o F; and subjective responses indicating limited spare cognitive capacity via Bedford scale have been observed during ground-based exploration EVA simulations in the NASA Active Response Gravity Offload Simulator (ARGOS) and Neutral Buoyancy Lab (NBL) during simulated planetary EVAs in pressurized suits. Further, ground-based EVA analogs vary in their ability to simulate planetary EVA and resulting physical workloads. DISCUSSION: Metabolic costs, thermal burdens, functional strength, and cognitive impacts have been and must continue to be assessed in ground-based analogs to fully characterize operational demands and crew readiness levels for exploration EVA. Considerations should be given to enabling a new concept of high-tempo surface EVA operations and associated work-rest intervals, understanding human health and performance impacts of evolving commercial suit designs and capabilities, and predictive modeling and decision support capabilities to enable safe and successful EVA operations.

EVA↗
NASA NTRS2024

Considerations for Health and Performance during Surface Extravehicular Activities

BACKGROUND: NASA’s objectives for expanding human presence beyond low Earth orbit will require Extravehicular Activities (EVAs) on lunar and planetary surfaces. Given the physiological and functional demands of conducting surface EVAs in a pressurized spacesuit in reduced gravity environments, there is a possibility that crew injury and compromised physiological and/or functional performance may present. OVERVIEW: Many human health and performance knowledge gaps exist in regards to exploration EVA that require characterization to ensure safety, reliability, and mission success. To address knowledge gaps, EVA simulations in Earth-based analog environments and/or spacesuit simulators can be utilized to provide valuable insights into task-based physiologic and metabolic costs, cognitive loads, and associated operational limitations to inform future mission concepts. Physical workloads approaching 60% of maximum metabolic rates and 85% age-predicted heart rate maxima; core body temperatures approaching 100° F; and subjective responses indicating limited spare cognitive capacity via Bedford scale have been observed during ground-based exploration EVA simulations in the NASA Active Response Gravity Offload Simulator (ARGOS) and Neutral Buoyancy Lab (NBL) during simulated planetary EVAs in pressurized suits. Further, ground-based EVA analogs vary in their ability to simulate planetary EVA and resulting physical workloads. DISCUSSION: Metabolic costs, thermal burdens, functional strength, and cognitive impacts have been and must continue to be assessed in ground-based analogs to fully characterize operational demands and crew readiness levels for exploration EVA. Considerations should be given to enabling a new concept of high-tempo surface EVA operations and associated work-rest intervals, understanding human health and performance impacts of evolving commercial suit designs and capabilities, and predictive modeling and decision support capabilities to enable safe and successful EVA operations.

P Estep↗
NASA NTRS2014

Exercise Effects on the Course of Gray Matter Changes Over 70 Days of Bed Rest

Long duration spaceflight affects posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes through direct effects on peripheral changes that result from reduced vestibular stimulation and body unloading. Effects of microgravity on sensorimotor function have been investigated on earth using bed rest studies. Long duration bed rest serves as a space-flight analogue because it mimics microgravity in body unloading and bodily fluid shifts. It has been hypothesized that the cephalad fluid shift that has been observed in microgravity could potentially affect central nervous system function and structure, and thereby indirectly affect sensorimotor or cognitive functioning. Preliminary results of one of our ongoing studies indeed showed that 70 days of long duration head down-tilt bed rest results in focal changes in gray matter volume from pre-bed rest to various time points during bed rest. These gray matter changes that could reflect fluid shifts as well as neuroplasticity were related to decrements in motor skills such as maintenance of equilibrium. In consideration of the health and performance of crewmembers both inand post-flight we are currently conducting a study that investigates the potential preventive effects of exercise on gray matter and motor performance changes that we observed over the course of bed rest. Numerous studies have shown beneficial effects of aerobic exercise on brain structure and cognitive performance in healthy and demented subjects over a large age range. We therefore hypothesized that an exercise intervention in bed rest could potentially mitigate or prevent the effects of bed rest on the central nervous system. Here we present preliminary outcomes of our study.

Koppelmans, V.↗
NASA NTRSDate not supplied

Manual Crew Override of Vehicle Landings Following G-Transitions

BACKGROUND Manual control during exploration spaceflight consists of both planned automated supervisory control and unplanned crew override. This crew override capability is critical to enable overall mission success during landing contingencies. However, the introduction of manual override capabilities must be implemented to enable crews to mitigate risks introduced by human error. Adaptive changes in the sensorimotor system can manifest during g-transitions as spatial disorientation. While training and landing aids enable successful landing through disorientation, these adaptive changes may increase cognitive demand that needs to be accounted for in the manual control strategy. It is important to characterize these effects as soon as possible following the G-transition to develop appropriate countermeasures. METHODS The following study seeks to inform the risk associated with altered sensorimotor and vestibular function impacting critical mission tasks. We aim to characterize the effects of short and long-duration weightlessness on manual control following G-transitions using simulated lunar landing on a six-degree-of-freedom (6DOF) motion base, a fixed base simulation, and a supervisory control tablet task. The primary goal is to understand the impact of spaceflight on crew ability to perform manual crew override and supervisory control. This aim will be assessed by comparing pre- versus postflight simulation performance in crewmembers assigned to either short duration (< 30 day) or long duration (~6- month) missions to the International Space Station (ISS). We hypothesize there will be postflight increases in the percent time that pilots are outside of the acceptable range for recommended vehicle state parameters and the reaction time for secondary cognitive tasks. Ground-based control subjects, who are demographically matched to the crew considering age (± 5 years) and gender, will undergo the same testing schedule as the crew to examine the effects of flight phase independent of microgravity exposure. The second aim is to examine how adaptive changes in vestibular and cognitive function relate to changes in manual crew override proficiency. Crew performance for a sensorimotor perceptual test battery will evaluate motion perception tracking, roll nulling, and/or vection sensitivity using the 6DOF motion base. We hypothesize that a higher severity of vestibular alterations will be associated with increased percent time outside of guidance limits. Motion sickness severity and sleepiness will also be evaluated. To determine the impact of “just-in-time” training, the third aim seeks to compare performance during on-board lunar landing tasks conducted late in-flight to early postflight. We hypothesize that proficiency on the “just-in-time” laptop trainer late in mission will be positively correlated with early postflight proficiency on the same task. The final aim will establish assessments of performance, training protocols, and the learning progression in a ground-control cohort of first-time users. RESULTS The assessment of the learning progression associated with the piloting task on the motion base system with thirty ground subjects will be reported. Learning curves will be established across four distinct sessions and within session considering trial difficulty. The difficulty of the landing task can be modulated with the landing divert distance and cross or downrange difficulty. Results may include changes in performance across multiple trials of a multi-attribute lunar tablet supervisory control task. Preliminary investigations of eighteen subjects who completed vestibular threshold and motion perception tasks offer expected performance ranges for upcoming preflight crew evaluations. The results yielded an average roll threshold of 0.46 ± 0.30 deg/s and an average roll nulling root mean square error performance of 2.52 ± 0.52 deg/s. RELEVANCE This project will deliver an operational demonstration of crew monitoring capability following spaceflight and identify potential deficits that may require remediation. Comparison of individual vestibular and cognitive changes with crew performance will help better characterize the manual control risks associated with sensorimotor alterations. Ground testing will evaluate learning progression, refine training protocols, and serve as a control cohort for comparisons to crew performance. ACKNOWLEDGEMENTS: The authors acknowledge contributions from Draper, the Dynamic Skills Trainer (DST) Lab, and the Software, Robotics, and Simulation Division toward the development of the lunar landing simulation platforms. This project is funded by the Human Health Countermeasures Element.

Hannah M. Weiss↗
DOE OSTI2024

In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer’s disease

The molecular mechanisms underlying neuronal dysfunction in Alzheimer’s disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant’s real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau’s synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2004

The effects of heavy particle irradiation on exploration and response to environmental change

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks. Published by Elsevier Ltd on behalf of COSPAR.

NASA Program Biomedical Research and Countermeasur↗
DOE OSTI2022

Association of AK4 Protein From Stem Cell–Derived Neurons With Cognitive Reserve

Background and Objectives: Identifying protein targets that provide cognitive reserve is a strategy to prevent and treat Alzheimer disease and Alzheimer disease related dementias (AD/ADRD). Previous studies using bulk human brain tissue reported 12 proteins associated with cognitive reserve. This study examined whether the same proteins from induced neurons (iNs) are associated with cognitive reserve of their human donors. Methods: Here, induced pluripotent stem cell (iPSC) lines were generated from cryopreserved peripheral blood mononuclear cells of older adults who were autopsied as part of the Religious Orders Study or Rush Memory and Aging Project. Neurons were induced from iPSCs using a standard neurogenin2 protocol. Tandem mass tag proteomics analyses were conducted on iNs day 21. Cognitive reserve of their human donors was measured as person-specific slopes of cognitive change not accounted for by common neuropathologies. Results: The 53 human donors died at a mean age of 91 years, all were non-Latino White, and 36 (67.9%) were female. Eighteen were diagnosed with Alzheimer dementia proximate to death, and 34 had pathologic AD diagnosis at autopsy. Approximately 60% of the donors had above-average cognitive reserve such that their cognition declined slower than an average person with comparable burdens of neuropathologies. Eight of the 12 candidate proteins were quantified in iNs proteomics analyses. Higher adenylate kinase 4 (AK4) expression in iNs was associated with lower cognitive reserve, consistent with the previous report for brain AK4 expression. Discussion: By replicating cortical protein associations with cognitive reserve in human iNs, these data provide a valuable molecular readout for studying complex clinical phenotypes such as cognitive reserve in a dish.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Distinct effects of beta-amyloid and tau on cortical thickness in cognitively healthy older adults

Published reports of associations between β-amyloid (Aβ) and cortical integrity conflict. Tau biomarkers may help elucidate the complex relationship between pathology and neurodegeneration in aging. We measured cortical thickness using magnetic resonance imaging, Aβ using Pittsburgh compound B positron emission tomography (PiB-PET), and tau using flortaucipir (FTP)-PET in 125 cognitively normal older adults. We examined relationships among PET measures, cortical thickness, and cognition. Cortical thickness was reduced in PiB+/FTP+ participants compared to the PiB+/FTP– and PiB–/FTP– groups. Continuous PiB associations with cortical thickness were weak but positive in FTP– participants and negative in FTP+. FTP strongly negatively predicted thickness regardless of PiB status. FTP was associated with memory and cortical thickness, and mediated the association of PiB with memory. Past findings linking Aβ and cortical thickness are likely weak due to opposing effects of Aβ on cortical thickness relative to tau burden. Tau, in contrast to Aβ, is strongly related to cortical thickness and memory.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer’s disease: A putative biomarker of amyloid-induced vascular damage

We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance. Additionally, we sought to replicate FLT1 interactions in the brain. The results showed that higher levels of FLT1 in CSF and post-mortem brain tissue related to increased tau, particularly among amyloid positive individuals. These analyses help clarify the potential utility of FLT1 as a biomarker among individuals with evidence of brain amyloidosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

The POINTER Imaging baseline cohort: Associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition

Abstract INTRODUCTION The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study. METHODS Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta‐amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk. RESULTS A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ−, Aβ+ (29%) participants were older, had higher apolipoprotein E (APOE) ε4 carriage rate and white matter hyperintensity volume, and greater temporal tau. FRS was related to MRI measures, but not AD biomarkers. FRS and tau had independent effects on cognition. DISCUSSION In this heterogenous, at‐risk cohort, CVD risk was related to more abnormal brain structure and poorer cognition, representing a putative non‐AD (Alzheimer's disease) pathway to brain injury and cognitive decline. Highlights The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort is enriched for cardiovascular disease (CVD) and poor lifestyle POINTER Imaging collected multimodal neuroimaging data in this unique, at‐risk cohort Amyloid burden was related to age, apolipoprotein E (APOE) ε4 carriage, and measures of disease progression Associations between amyloid and tau, and tau and cognition, were relatively weak CVD risk and tau pathology were independently related to memory

Neurosciences & Neurology↗
NASA NTRS2015

Daytime Cognitive Performance in Response to Sunlight or Fluorescent Light Controlling for Sleep Duration

Light is the primary synchronizer of the human circadian rhythm and also has acute alerting effects. Our study involves and comparing the alertness, performance and sleep of participants in the NASA Ames Sustainability Base, which uses sunlight as its primary light source, to in a traditional office building which uses overhead florescent lighting and varying exposure to natural light. The purpose of this study is to determine whether the use of natural lighting as a primary light source improves daytime cognitive function and promotes nighttime sleep. Participants from the Sustainability Base will be matched by gender and age to individuals working in other NASA buildings. In a prior study we found no differences in performance between those working in the Sustainability Base and those working in other buildings. Unexpectedly, we found that the average sleep duration among participants in both buildings was short, which likely obscured our ability to detect a difference the effect of light exposure on alertness. Given that such sleep deprivation has negative effects on cognitive performance, in this iteration of the study we are asking the participants to maintain a regular schedule with eight hours in bed each night in order to control for the effect of self-selected sleep restriction. Over the course of one week, we will ask the participants to wear actiwatches continuously, complete a psychomotor vigilance task (PVT) and digit symbol substitution task (DSST) three times per day, and keep daily sleepwork diaries. We hope that this study will provide data to support the idea that natural lighting and green architectural design are optimal to enhance healthy nighttime sleep patterns and daytime cognitive performance.

cognitive performance↗
DOE OSTI2024

Individuals with Alzheimer's disease and low tau burden: Characteristics and implications

Abnormal amyloid-beta (Aβ) and tau deposition define Alzheimer's Disease (AD), but non-elevated tau is relatively frequent in patients on the AD pathway. We examined characteristics and regional patterns of 397 Aβ+ unimpaired and impaired individuals with low tau (A+T-) in relation to their higher tau counterparts (A+T+). Seventy-one percent of Aβ+ unimpaired and 42% of impaired Aβ+ individuals were categorized as A+T- based on global tau. In impaired individuals only, A+T- status was associated with older age, male sex, and greater cardiovascular risk. α-synuclein was linked to poorer cognition, particularly when tau was low. Tau burden was most frequently elevated in a common set of temporal regions regardless of T+/T- status. Low tau is relatively common in patients on the AD pathway and is linked to comorbidities that contribute to impairment. These findings have implications for the selection of individuals for Aβ- and tau-modifying therapies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

In-Home Mobility Frequency and Stability in Older Adults Living Alone With or Without MCI: Introduction of New Metrics

Background: Older adults spend a considerable amount of time inside their residences; however, most research investigates out-of-home mobility and its health correlates. We measured indoor mobility using room-to-room transitions, tested their psychometric properties, and correlated indoor mobility with cognitive and functional status. Materials and Methods: Community-dwelling older adults living alone ( n = 139; age = 78.1 ± 8.6 years) from the Oregon Center for Aging & Technology (ORCATECH) and Minority Aging Research Study (MARS) were included in the study. Two indoor mobility features were developed using non-parametric parameters (frequency; stability): Indoor mobility frequency (room-to-room transitions/day) was detected using passive infrared (PIR) motion sensors fixed on the walls in four geographic locations (bathroom; bedroom; kitchen; living room) and using door contact sensors attached to the egress door in the entrance. Indoor mobility stability was estimated by variances of number of room-to-room transitions over a week. Test-retest reliability (Intra-class coefficient, ICC) and the minimal clinically important difference (MCID) defined as the standard error of measurement (SEM) were generated. Generalized estimating equations models related mobility features with mild cognitive impairment (MCI) and functional status (gait speed). Results: An average of 206 days (±127) of sensor data were analyzed per individual. Indoor mobility frequency and stability showed good to excellent test-retest reliability (ICCs = 0.91[0.88–0.94]; 0.59[0.48–0.70]). The MCIDs of mobility frequency and mobility stability were 18 and 0.09, respectively. On average, a higher indoor mobility frequency was associated with faster gait speed (β = 0.53, p = 0.04), suggesting an increase of 5.3 room-to-room transitions per day was associated with an increase of 10 cm/s gait speed. A decrease in mobility stability was associated with MCI (β = −0.04, p = 0.03). Discussion: Mobility frequency and stability in the home are clinically meaningful and reliable features. Pervasive-sensing systems deployed in homes can objectively reveal cognitive and functional status in older adults who live alone.

Wu, Chao-Yi↗
NASA NTRSDate not supplied

Effects Of Five-Ion Galactic Cosmic Radiation Simulation On Immune Function, Brain, And Behavior In Male And Female Mice

Exposure to galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. To simulate the type of radiation exposure occurring during spaceflight, model organisms can be exposed to relevant doses via Five-Ion Galactic Cosmic Radiation Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. We have investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy. Following exposure, immune, brain and behavioral (sensorimotor, risk-taking and cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Moon and Mars. There were pronounced sex differences observed in all outcome measurements, while very few radiation induced effects were observed. Those dose effects that were observed were primarily in cytokine expression and less so in behavioral measurements. Further studies will investigate if radiation, microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance, ultimately to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions.

Stephanie Puukila↗
NASA NTRSDate not supplied

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

Stephanie Puukila↗