bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Cortical Demyelination in Geriatric Mild Traumatic Brain Injury and Alzheimer’s Disease
Authors: Wang Shania , Chowdhury Nahian , Mahoney Sean , Irimia Andrei
Published: December 2021

Mild traumatic brain injury (mTBI) accelerates the rate of age-associated brain atrophy, whose pattern resembles the cortical neurodegeneration pattern observed in Alzheimer’s disease (AD). Because the ratio R of T1-to-T2-weighted magnetic resonance imaging (MRI) intensities is a surrogate measure of cortical myelin concentration, mapping and quantifying changes in this ratio can improve our understanding of demyelination after geriatric mTBI and AD. T1- and T2-weighted MRIs were acquired acutely and ~6 months post-injury from 68 healthy controls (HCs, age (years, y): μ = 76 y, σ = 4 y), 19 mTBIs (age μ = 70 y, σ = 5 y), and 33 ADs (age μ = 77, σ = 6). Volumes were co-registered using 3D Slicer’s BRAINSFit module, and T2-constrained segmentations of T1 volumes were obtained using FreeSurfer. R and its time changes were computed at each cortical location. When comparing mTBI and AD patients to HCs, significant differences in R were found across ~10% and ~23% of the cortex, respectively (p < 0.05). When comparing mTBI to AD, the former exhibited significantly less myelin content in the lateral, medial, and ventral temporal lobes (p < 0.05), on the medial aspects of superior parietal lobules and superior frontal gyri (p < 0.05), and in orbital gyri (p < 0.05), whereas AD subjects had less myelin content on lateral aspect of the parietal lobe (p < 0.05). These results highlight demyelination differences in mTBI and AD. Future studies should examine the long-term trajectories to quantify the risk of neurodegenerative disease after mTBI.
Local Atrophy Observed in Subjective Cognitive Decline Varies Based on Questionnaire Employed in ADNI
Authors: Morrison Cassandra , Dadar Mahsa , shafiee Neda , Collins Louis
Published: December 2021

Background: Subjective cognitive decline (SCD) may be associated with increased risk for Alzheimer’s disease. However, neither research nor clinical practices have implemented a universal approach to operationalize SCD. This study was designed to determine whether four different methods of defining SCD influence atrophy differences observed between SCD and normal controls (NC). Methods: We included MRI scans from 273 participants (NC and SCD) from the Alzheimer’s Disease Neuroimaging Initiative. We used four methods to operationalize SCD: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), Worry, and ECog+Worry. Deformation-based morphometry was performed to examine volumetric change at the lateral ventricles, amygdala, and superior temporal regions (CerebrA atlas; Manera et al., 2020)). A previously validated MRI analysis method (SNIPE) was used for volume and grading of the hippocampus and entorhinal cortex (Coupe et al., 2012). A logistic regression was completed to examine the association between diagnosis and atrophy in SCD and NC. Results: Left hippocampal grading was lower in SCD than NC with the CCI (p=.041) and Worry (p=.021). When using ECog+Worry, smaller left entorhinal volume was observed in SCD than NC (p=.025). Both the right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD than NC, with only the ECog. Conclusion: Although SCD questionnaires are designed to measure the same construct, the results here suggest otherwise. These results suggest that the SCD questionnaire employed will influence whether atrophy is observed in SCD relative to NC. Future research is warranted to better understand how different methodologies result in inconsistent findings.
Remyelination Improves Voiding Dysfunction in a Mouse Model of Multiple Sclerosis
Authors: Ramasamy Ramalakshmi , Hardy Cara , Crocker Stephen , Smith Phillip
Published: December 2021

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of note, over 80% of MS patients have urinary symptoms as one of their earliest symptoms. Since MS patients often live into older age, urinary incontinence and retention are significant problems affecting their quality of life. Although several studies show that inflammatory-demyelinating animal models of MS develop bladder dysfunction, the confounding influence of systemic inflammation in these models limits potential interpretation on the contribution of CNS-myelination to bladder dysfunction. We sought to address this knowledge gap using the cuprizone model of demyelination and remyelination. C57Bl/6 mice were treated with dietary cuprizone (0.2%w/w) for four weeks to induce demyelination. One group was allowed four additional weeks for recovery and remyelination. We performed voiding spot assay (VSA), urethane-anesthetized cystometry, and CNS-histology to assess demyelination-induced differences in urinary performance. We observed that cortical demyelination causes significant aberrance in voiding behavior (conscious cortical control) characterized by increased micturition frequency and reduced volume per micturition. Interestingly, remyelination restored healthy bladder function. However, there were no significant changes in the cystometric parameters (brainstem reflex) between the treatment groups. While MS is not classically considered a disease of aging, extending the longevity of these patients has not been reciprocated with improved treatments for their most-bothersome conditions, notably urinary symptoms that persist throughout life. Our data represent a novel compelling connection and strong correlation between CNS-myelination and cortical control of bladder function, which has potential implications in MS, aging, and aging-associated neurological disorders.
Senolytics in a Model of Alzheimer's Disease
Authors: Wang Ellen , Lee Suckwon
Published: December 2021

The therapeutic effects of senescent cell killing with senolytics in neurodegeneration mouse models poise this strategy as an intervention candidate for Alzheimer’s Disease (AD). However, it is unclear whether senolytic therapies for AD are translatable to human cells. To determine whether senolytics could be a viable therapeutic for AD, we have treated long-term mixed human neuron/astrocyte primary cultures with amyloid beta oligomers (ABO), which we have shown to induce a phenotype consistent with senescence in neurons. Fifteen days after ABO treatment, we administered Navitoclax (Nav) and the natural killer cell-line NK92, which are known to selectively kill senescent cells in the periphery. Following treatment, we assessed senescence markers in our cultures as well as senescent cell killing selectivity through cleaved Caspase 3 quantification. Our preliminary data show that Nav (8, 4, and 0.5uM) kills both control and ABO treated cells. NK92 cells (10 to 1 effector to target ratio) also kill some control cells, suggesting there is not a clear cut mechanism by which NK92 cells can distinguish senescent from non-senescent neurons or astrocytes. Although analysis of selective killing is ongoing, off-target killing indicates that we need more refined senolytic strategies to implement their safe human use.
The Human Genes That Link Middle-Age Comorbidities And Alzheimer’s Disease
Authors: Murakami Shin
Published: December 2021

Advancements in biomedical research have identified the genes influencing life spans, stress resistance and age-related diseases, including Alzheimer’s disease. Stress resistance includes resistance to multiple forms of stress, pathogens and toxic beta-amyloid which is tightly associated with Alzheimer’s disease. We have investigated 431 human genes that are associated with co-morbidities (Vahdati Nia et al, 2017; Le et al., 2020). Those genes are involved in lipid metabolism, hemostasis, hemostasis, neuroendocrine and immune functions. The genes are relevant to middle-life health. We explore a wide variety of co-morbidities that could happen in middle to late life. I will give a brief review of increased stress resistance, and genetic markers associated with co-morbidities. I will discuss how the studies may benefit to fight against COVID-19. References: 1. Vahdati Nia B, Kang C, Tran MG, Lee D, Murakami, S. (2017) Front. Genet. 8:55. doi: 10.3389/fgene.2017.00055 2. Le D, Crouch N, Villanueva A, Phong Ta, Dmitriyev R, Tunzi M, and Murakami S. (2020) Journal of Neurology and Experimental Neuroscience. 6;S1.
Strategies for implementing music-based interventions for people with dementia: A systematic review
Authors: Amano Takashi , Strong Joe , Hooley Cole , Inoue Megumi
Published: December 2021

Previous research has found that music-based interventions are effective at improving several outcomes related to dementia for nursing home residents. Some studies have investigated the implementation of music-based interventions. However, to date, there is no synthesis available regarding strategies and outcomes of these implementation studies. This study aims to synthesize available evidence regarding implementation strategies and outcomes of music-based interventions for nursing home residents with dementia. We conducted a systematic literature search in PsychInfo, PubMed, MEDLINE, CINAHL, and The Cochrane Library. A total of 8 studies were included for the qualitative synthesis. Of the eight studies, half were studies of music therapy and the other half were on individualized music. We identified 49 implementation strategies. The most frequently reported category of strategies was planning (34.7%), followed by education (24.5%), quality management (24.5%), restructuring (12.2%), and finance (4.1%). No strategies under the category of attending to the policy context were reported. We identified 21 implementation outcomes. The most frequently reported category was adoption (33.3%), followed by fidelity (28.6%), appropriateness (19.0%), sustainability (9.5%), acceptability (4.8%), and cost (4.8%). No studies measured feasibility or penetration. Although various implementation strategies have been utilized, most of them are under the categories related to intervention methods. Less attention has been paid to strategies that aim at structural changes of intervention delivery systems. Future studies should investigate facilitators and barriers of implementing music-based interventions especially focusing on organizational and structural aspects.
Association of Blood Cell Parameters of Peripheral Inflammation With Brain Imaging Measures
Authors: Fang Yuan , Lunetta Kathryn , Satizabal Claudia , Alosco Michael , Mez Jesse , Qiu Wendy , Doyle Margaret , Murabito Joanne
Published: December 2021

Neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), are easily measured circulating blood cell parameters that reflect chronic peripheral inflammation which increases risk for dementia and Alzheimer’s disease (AD). We investigated the cross-sectional association between these blood cell parameters and brain MRI measures, including total cerebral brain volume (TCBV) as percentage of total intracranial volume (TCV) to correct for differences in head size, hippocampal volume (HPV) and log transformed white matter hyperintensity (WMH) volume, in the Framingham Heart Study (FHS) cohorts. We identified 2882 FHS participants 25 to 92 years of age (mean 59 years), 53% women, who attended an exam that included a complete blood cell count sample and received a brain MRI within five years of blood draw. We used linear mixed effect models to examine associations, adjusting for age, age^2, sex, education, cohort, time between blood draw and MRI, prevalent cardiovascular disease, C-reactive protein, APOE-ϵ4 genotype and TCV for HPV and WMH, and accounting for familial correlation using a random effect. We observed significant (p≤0.01) associations between higher RDW and smaller TCBV, and between elevated NLR and larger WMH volume. Analysis on an older subgroup (age ≥60 years, mean 71 years, n=1357) demonstrated larger effect sizes and additional significance between increased RDW with smaller HPV. We conclude that chronic peripheral inflammation as measured by NLR and RDW associates with MRI measures of brain aging (TCBV, HPV) and vascular brain injury (WMH) in FHS, with stronger impact in participants ≥60 years.
Predictors of Behavioral and Psychological Symptoms in Community-Dwelling Older Adults With Dementia
Authors: Kang Bada , Cho Eunhee , Kim Sujin , Hwang Sinwoo , Kwon Eunji , Heo Seok-Jae , Lee Jun Hong , Ye Byoung Seok
Published: December 2021

Although disclosing the predictors of different behavioral and psychological symptoms of dementia (BPSD) is the first step in developing person-centered interventions, the current understanding is limited as it considers BPSD as a homogenous construct, not accounting for its heterogeneity. Therefore, this study explored the predictors of BPSD subsyndromes, and built prediction models for these subsyndromes in community-dwelling older adults with dementia in Korea. This prospective study consisted of a two-wave dataset. We fit the generalized linear mixed models using Wave 1 data (N = 145) and then validated them using Wave 2 data (N = 59). BPSD and their proximal factors were assessed on a daily basis using diaries written by family caregivers. Sleep and activity levels were objectively measured using actigraphy. The amount of nighttime sleep hours was significantly associated with next-day sleep and nighttime behaviors (OR = 0.87; p = 0.005), with the amounts of energy expenditure showing significant association with euphoria/elation (OR = 0.02; p = 0.019). All subsyndromes except euphoria/elation were found to be significantly associated with either hunger, thirst, urination, or bowl movement; with all BPSD showing a significant association with environmental changes. We also found several background factors, including premorbid personality and taking sedatives as predictors for specific subsyndromes. The area under the receiver operating characteristic curve scores for the data were greater than 0.9 and 0.8 in Waves 1 and 2, respectively, across all subsyndromes. Prediction models for BPSD will help in the development of symptom-targeted, individualized interventions.
State-Level Policy Actions to Support Family Caregivers
Authors: Evans Molly
Published: December 2021

The stresses created by the growing need for family caregivers have failed to prompt federal policy action; in its absence, states are stepping up. This review of state policies that support employment among family caregivers found six main categories of legislative action: paid leave; expanding federally mandated unpaid leave; paid sick time; unemployment insurance for job loss attributable to caregiving duties; establishing family caregivers as a protected classification in employment discrimination; and flexible or alternative work schedules. Despite the demand for policies that support and empower working caregivers, a minority of states have passed such legislation; to date, 9 states have implemented paid family leave; 14 have implemented mandatory sick leave legislation; and 14 have expanded FMLA. This study discusses state-level policy actions, reviews the status and importance of these policies, and finds that despite gaps in caregiver support legislation at the state level, there is significant and promising momentum.
A Phase I Trial Assessing Lomecel-B Infusion in Individuals with Alzheimer’s Disease: Study Design and Rationale
Authors: Ramdas Kevin , Yousefi Keyvan , Hitchinson Ben , McClain-Moss Lisa , Diaz Liliana , Baumel Barry , Hare Joshua , Oliva Anthony
Published: December 2021

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder characterized by memory loss and persistent cognitive dysfunction which significantly compromises quality of life. Brain inflammation is a prominent feature of AD pathology. Lomecel-B which is derived from culture-expanded medicinal signaling cells (MSCs) have immuno-modulatory capacity and control inflammation and the cytokine production of lymphocytes. The primary objective of this study was to evaluate the safety of Lomecel-B infused intravenously in individuals with AD. Safety was monitored by examining vital signs, physical and neurological exams, laboratory tests (hematology, coagulation, blood chemistry, and urinalysis). This was a multicenter phase 1 double-blinded, placebo controlled trial initiated with a safety run in phase of 3 individuals followed by a randomized phase of 28 individuals. During the safety run-in phase all subjects were treated with low dose Lomecel-B no less than 5 days apart, and evaluated for safety. In the randomized phase, subjects were treated with either low or high dose Lomecel- B or Placebo in a 2:2:1 randomization ratio. The study enrolled adults aged 50-80 years diagnosed with AD via confirmatory brain MRI and PET scan and a MMSE score of 18-24. Safety and efficacy assessments were completed at 30, 90, 180, 270 and 365 days. We describe the design and rationale for this phase 1 trial with the primary objective of assessing the safety of Lomecel-B on adults with AD. The secondary efficacy measurements included ADAS-Cog 11, MMSE, TMT, UPSIT, GDS, blood biomarkers and numerous quality of life questionnaires.
Comparison of Cognitive Intervention Delivery Formats in Patients with Dementia-A Network Meta-analysis
Authors: Sun Yue , Wang Zhi-wen
Published: December 2021

Cognitive intervention has been shown to be effective to delay cognitive decline in older adults with dementia. However, whether cognitive intervention could be effectively delivered in individual, group, telephone, guided self-help and unguided self-help formats remains unclear. Pubmed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), CINAHL, the Cochrane Central Register of Controlled Trials, Web of science, China National Knowledge Infrastructure database, Chinese Biomedical Literature database and Wan Fang database were systematically searched. 3419 records were extracted, quality assessed, and double-blind screened by 2 authors. Totally 51 studies were included which enrolled 3388 participants. Network meta-analysis (NMA) was conducted to evaluate the relative effects and rank probability of different cognitive intervention delivery formats. For older adults with dementia, guided self-help, group and individual cognitive intervention delivery formats appeared effective in improving the cognitive function, while telephone and unguided self-help were not significantly inferior to control condition. Guided self-help had the highest probability of being the best treatment among the five cognitive intervention delivery formats. Health-care professionals should apply personalized cognitive intervention format based on individual condition and preferences.
Hippocampal Volume Is Smaller In Female Double Carriers Of Two Strongest AD Genetic Risk Factors
Authors: Ukraintseva Svetlana , Popov Vladimir , Arbeev Konstantin , Duan Hongzhe , Bagley Olivia , Kulminski Alexander , Yashin Anatoliy
Published: December 2021

Genetic risk factors for Alzheimer’s disease (AD) may facilitate AD-related changes in the brain long before AD clinical manifestation. While APOE4 was linked to a reduced hippocampal volume (HV) in a number of studies, the impact of rs2075650, another polymorphism strongly associated with AD, on HV is less clear. The rs2075650 (in TOMM40) is only in moderate to low LD with APOE4, and may have independent effects on HV or interact with APOE4. We studied associations of rs2075650 (G allele, risk factor for AD), rs429358 (C allele, proxy for APOE4), and their combinations, with right HV measured by MRI, among 10,738 women and 9,775 men aged 60-75, from UK Biobank. We found that right HV was significantly (p<0.02) smaller in women who carry both AD risk variants (rs2075650(G) and rs429358(C)), than in non-carriers of both of these variants, while having only one risk variant (G or C) didn’t clearly affect HV. The studied associations didn’t reach statistical significance in men. Our results suggest that rs2075650(G) and rs429358(C) may contribute synergistically to a reduction in hippocampus volume, in females only, and support the role of interactions between genetic risk factors for AD in sex differences in preclinical biomarkers of AD pathology.
Hypertensive disorders of pregnancy and risk of Alzheimer’s disease, vascular dementia, and other related dementia
Authors: Schliep Karen , Zhang Yue , Tschanz Joanne , Majersik Jennifer , Facelli Julio , Varner Michael
Published: December 2021

Several recent studies have examined whether hypertensive disorders of pregnancy (HDP) are associated with an increased risk for Alzheimer’s disease (AD) and other related dementias (RD) with conflicting findings. Limitations to prior studies include lack of assessing risk by dementia subtype, inadequate sample sizes, and not fully exploring the role of mid-life factors. We performed a retrospective matched cohort study among women with >1 singleton pregnancy (1939–2013) using the Utah Population Database. HDP-exposed women (n=19,989) were one-to-two matched with unexposed women (n=39,679) by 5-year age groups, year of childbirth (within 1 year), and parity (1, 2, 3, 4, ≥5) at the time of the pregnancy. HDP pregnancies were complicated by preeclampsia (62%), gestational hypertension (34%), and eclampsia (4%). Women with a history of HDP had a higher hazard of all-cause dementia (HR=1.37; 95% CI: 1.26, 1.50) compared to women without a history of HDP after adjustment for maternal age, year of childbirth, and parity. The hazard doubled after additionally accounting for pre-pregnancy BMI (HR=2.31; 95% CI: 1.24, 4.32). Stratifying by dementia subtype, we found HDP to be associated with a higher hazard of vascular dementia (HR=1.64; 95% CI: 1.19, 2.26) and other related dementia (HR=1.49; 95% CI: 1.34, 1.65) but not Alzheimer’s disease (HR=1.04; 95% CI: 0.87, 1.24) after accounting for competing risks. Mid-life hypertension and stroke were found to have the greatest mid-life impact, mediating 43% and 41% of dementia risk, respectively, highlighting women who may most benefit from close surveillance and early preventive and clinical interventions.
The Relationship Between Neuropsychiatric Symptoms, Nighttime Behaviors, and Alzheimer’s Disease CSF Biomarkers
Authors: Zhang Meina , Cho Young-Eun , Moon Chooza
Published: December 2021

Alzheimer's disease (AD) commonly involves neuropsychiatric symptoms (NPS), such as nighttime behaviors (or sleep disturbance), hallucination, delusion, or mood changes. However, it is unclear how NPS and sleep disturbances are correlated with AD biomarkers. The purpose of this analysis was to examine how NPS and nighttime behaviors are associated with AD CSF biomarkers by cognitive status. A total of 1,667 subjects’ (mean age = 69.4 SD=9.3, 48 % (808) were male) data from the National Alzheimer’s Disease Coordinating Center (NACC) were used, including subjects with dementia (n = 577), mild cognitive impairment (MCI, n = 363), cognitive impairment but not MCI (n = 47), cognitive impairment due to Alzheimer’s etiology (n= 608), and normal cognition (n = 680). The nighttime symptoms, number, and severity of NPS were assessed using the Neuropsychiatric Inventory Questionnaire Quick Version (NPI-Q). Cerebrospinal fluid (CSF) samples were analyzed for Aβ42,dft5 t-tau, p-tau. We used generalized linear models to explore the associations accounting for age, sex, APOE4 alleles, and BMI. We found the number of NPS were associated with Aβ42 (p = 0.042) in individuals with MCI, impaired, or dementia due to Alzheimer’s etiology. Yet, the number of NPS were not associated with t-tau or p-tau in individuals with and without dementia. The severity of NPS including nighttime symptoms were not associated with biomarkers. Our results could suggest that the number of NPS can be reflected by higher CSF Aβ42 levels in the individuals with Alzheimer’s etiology. Future longitudinal analyses are warranted to understand the causal relationships.
Undesirable Weight Change and Reduced Sleep Quality in University Older Employees During the COVID-19 Pandemic
Authors: Butt Hamza , Insel Kathleen , Jason Kendra , Wager Mark , Robles Dagoberto , Yang Yunjia
Published: December 2021

This study investigated the occurrence of undesirable weight change (UDWC) and reduced sleep quality (RSQ), and major factors associated with these changes during COVID-19 pandemic amongst university older employees (age 50+). Participants (n = 846) were recruited throughout campus and completed an online survey. Summary statistics were used to describe characteristics of the study participants and frequency and level of UDWC and RSQ. Proportional odds models were used to assess major factors associated with UDWC and RSQ. The results showed 416 (43.2%) participants reported UDWC and 474 (49.2%) RSQ. Age was inversely, and obesity positively associated with UDWC and RSQ. With each 5-year increase in age, the OR (95% CI) was 0.87 (0.78, 0.97) for reporting UDWC and 0.90 (0.81, 1.00) for reporting RSQ. Obese individuals were significantly more likely to report a worse UDWC and RSQ (OR (95% CI) = 1.58 (1.18, 2.11) and 1.56 (1.16, 2.10) respectively).
Technology Use, Comfort, and Interest: A comparison between caregiver and older adult populations
Authors: Hubner Sarah , Chataut Akankshya , Shade Marcia , Fruhling Ann , Manley Natalie , Walls Meaghan Fitzgerald , Boron Julie Blaskewicz
Published: December 2021

Remaining community-dwelling is a goal for most aging adults; however, this may necessitate assistance from caregivers. To reduce burden and improve adult autonomy, recent technological advancements have provided various supports. These advancements may improve quality of life (QOL) while also enhancing psychological/physical well-being for adults and caregivers. To investigate relationships between technology, QOL, and caregiver burden, needs assessments with focus groups were utilized. Four older adult focus groups (N=20) and three caregiver focus groups (N=12) were convened. Older adult participants, aged 64-83 years (M=73.1,SD=5.3), were 50% female and generally white (90%). Caregiver participants, aged 31-78 years (M=61.9,SD=12.6), were majority female (83%) and generally white (92%). Because of the ongoing COVID-19 pandemic, focus groups were conducted via Zoom video-conferencing. Thematic analyses revealed major themes of privacy, transportation, and interest in streamlined technologies. Throughout groups, privacy was consistently described; participants were either 1) apathetic, noting absence of privacy or 2) hyper-vigilant about security, citing privacy as a major barrier to utilization. Transportation, specifically self-driving/enhanced vehicles, emerged as a focus for future technologies as a means to reduce care burden and improve personal autonomy/QOL. In general, participants noted that major barriers to technology use included complexity and cost; persons expressed interest in simpler/cheaper devices. This study indicates varied interest in technology while exposing barriers to use. Additionally, the methodology demonstrates the utility of technology (e.g., Zoom) in accessing vulnerable and/or isolated populations. Overall, understanding barriers to technology use and adoption informs upcoming developments and may improve accessibility and usefulness in future systems/devices.
What Factors are Associated with Facilitating Conditions to Use Gerontechnology?
Authors: Park Hayoung , Joo Susanna , Kim DaeEun , Kim YoonMyung , Jun Hey Jung
Published: December 2021

The purpose of this study is to explore relevant factors associated with facilitating conditions to use gerontechnology among Korean older adults. The sample was 310 Korean older adults aged 65 and above without cognitive impairment who participated in an online survey. The facilitating conditions to use gerontechnology were measured by the sum of five questions about basic knowledge, available help, financial resources, accessibility, and social influences of using gerontechnology from the Senior Technology Acceptance Model (STAM). Possible relevant factors comprised socio-demographic characteristics, physical and mental health, environmental factors, and social relationships. The results from the linear regression analyses showed that employment status, household income, cognitive function, social activity participation, and support from friends or neighbors were significantly associated with facilitating conditions to use gerontechnology. Older adults who are employed, have higher household income, have better cognitive functions, participate more in social activities, and receive higher levels of support from friends or neighbors tend to be in more facilitating conditions to use gerontechnology. The findings from this study imply the necessity of facilitating conditions to use gerontechnology as social policies for older adults who are unemployed, have lower household income, have worse cognitive functions, and have fewer social resources. This study is meaningful in that it has empirically explored various factors related to facilitating conditions to use gerontechnology for older adults based on the STAM. Future studies are needed to explore significant factors associated with facilitating conditions to use gerontechnology via various contexts.
Who Matters For The Subjective Perceptions Toward Gerontechnology?
Authors: Joo Susanna , Kim Seong Hee , Lee Changmin , Kim Chang Oh , Lim Yun Mook , Jun Hey Jung
Published: December 2021

The present study aims to investigate how personal relationship satisfaction moderate the associations between types of social support providers and the subjective perceptions toward gerontechnology among Korean older adults. Data were collected by an online survey in February 2021. The sample was 256 older Koreans who have a partner and children (N=109 older adults with low personal relationship satisfaction, N=147 older adults with high personal relationship satisfaction, Age: 66-88, M=69.91, SD=4.19). The dependent variables for the subjective perceptions toward gerontechnology were attitude toward using gerontechnology and anxiety for gerontechnology. Independent variables were four types of social support providers (spouse, children, siblings/relatives, and friends/neighbor). Personal relationship satisfaction was a binary moderator, dividing the sample into low and high personal relationship satisfaction groups. We applied multigroup structural equation modeling. The results showed associations between social support providers and subjective perceptions toward gerontechnology differed by the quality of personal relationships. In detail, receiving support from spouses was associated with the lower level of anxiety of using gerontechnology among older adults in the low personal relationship satisfaction group. Moreover, receiving support from spouses was associated with a higher level of attitude toward using gerontechnology in the high personal relationship group. Receiving social support from other providers were not significant in both groups. The findings imply that the partner living with was salience for positive perception toward gerontechnology. Furthermore, support from spouses may differently work on the subjective perception toward gerontechnology by the quality of personal relationships.
Caregiver Challenges of Older University Employees During the COVID-19 Pandemic
Authors: Kenning Heather , Yang Yunjia , O'Neill Lisa , Fain Mindy , Wager Mark , Sokan Amanda
Published: December 2021

The COVID-19 pandemic has created numerous challenges for older employees who are also caregivers. Some challenges are associated with disruptions in community-based support services leading to the intensification of caregiver responsibilities. Other challenges are related to caregivers’ concerns about their health or the risk of bringing the virus to the care recipient. This study investigated the impacts of those challenges on older (age 55+) working caregivers, from a major university, with a sample that included 57 male and 80 female caregivers. The investigation explored the association of gender and perception of COVID risk, vulnerability, loneliness, resilience, and interpersonal change. Although literature suggests that female caregivers report more risk-perception, stress, and overburden than male caregivers, our findings showed no significant differences based on gender. These findings suggest the importance of understanding that both male and female older working caregivers have been affected by stress and overburden due to the recent pandemic.
Differentially Methylated Genes in Muscle Associated with Gait Speed in a Non-Human Primate Model of Aging
Authors: Quillen Ellen , Frye Brett , Wildeman Bethany , Stainback Maggie , Register Thomas , Shively Carol
Published: December 2021

Age-related changes in DNA methylation are potent regulators of gene expression and may in part explain the onset of disease and disability. Vervet monkeys are a well-described model of neurocognitive and physical aging. Like humans, gait speed declines with age in vervets, and variability in gait speed in older animals is associated with age-related musculoskeletal and cognitive decline. To identify methylation patterns linked to aging-related physical decline, we investigated differentially methylated loci in vastus lateralis biopsies of 29 female vervets aged 8-28 years (~25-90 years in humans). We evaluated 107,490 loci on the Illumina Infinium Methylation EPIC Human Array that aligned with high fidelity to the vervet genome using the R package minfi and fit generalized linear mixed models to account for underlying genetic relatedness. We found 13 CpG methylation sites associated with 12 genes (CALCR, EBF4, GDNF, GMCL1, HAND1, HOXC10, IRX2, LBX2, MPPED2, SHISA6, SOX2, and WNT2) significantly differentially methylated with gait speed. Increased methylation was negatively associated with gait speed for all loci except GMCL1, reflecting the pattern of global hypermethylation of skeletal muscle tissue with age. Several of the associated genes are involved in development and differentiation including HOXC10 and LBX2, which regulates myoblast migration. CACNG8 regulates voltage-dependent calcium gated channels, and GDNF promotes motor neuron innervation of skeletal muscle. Most associations with muscle phenotypes are novel, but several have been linked to age-related bone diseases. We are currently evaluating the relationships of these differentially methylated loci with muscle mRNA expression and protein abundance.
Epigenetic Signature of Childhood Adversity in Older Adults
Authors: Klopack Eric , Crimmins Eileen
Published: December 2021

Past research has shown that childhood adversity (CA) affects the health of older adults; however, the biological mechanisms underlying this association are unclear. Though past research has implicated DNA methylation (DNAm), studies utilizing representative data from older adults and reliable DNAm measures are needed to answer key questions about how stable DNAm changes associated with CA are in later life. Methylation risk scores (MRSs) are an emerging tool that can be used as biomarkers of exposure and as a dimension reduction approach for mediation analyses. This study clarifies the association between CA and later life health by generating MRSs for childhood adversity based on an epigenome wide association study conducted in an independent sample and validating that measure in a nationally representative sample of older adults living in the US from the Health and Retirement Study (HRS), including 2016 methylation data from the HRS Innovative Subsample of the Venous Blood Study. For these 4,018 respondents, DNAm was assessed in whole blood using the Illumina Infinium Human Methylation EPIC BeadChip microarray. Results indicate that retrospective report of childhood SES is significantly associated with an MRS for CA after controlling for demographic factors (viz., race and ethnicity, age, gender, smoking status, and BMI), suggesting that DNAm signal from CA persists across the life course into older adulthood. This study helps clarify the biological processes underlying the association between CA and adult health.
Epigenetic Trajectories of Aging and Reprogramming
Authors: Niimi Peter , Levine Morgan , Meer and Margarita
Published: December 2021

The epigenetic landscape is remodeled with age, bringing about widespread consequences for cell function. With the revolutionary discoveries by Yamanaka and Takahashi, as well as those that built on this work, the transcription factors Oct4, Sox2, KLF4, and C-Myc (OSKM) can be expressed in a variety of cells, including fibroblasts, to make iPSCs. Once cells are reprogrammed, they show an erasure of epigenetic remodeling, suggesting an avenue to reverse aging. It has been recently shown that ectopic expression of three factors, OSK, can restore vision in mouse glaucoma model and reduces epigenetic age. It is not known the path epigenetic remodeling takes or whether all three factors, OSK, are required to remodel the epigenetic landscape. We hypothesize that during reprogramming, cells will reverse along a similar path they took during aging and eventually reverse along that path they took during differentiation. Alternatively, it may also be possible that cells take entirely new paths to reach a state of partial reprogramming or pluripotency. We used DNA methylation and RNA-seq as a multi-omics approach to map the trajectories cells make during aging, differentiation, and reprogramming. In human fibroblasts and hepatocytes, we tested the three-factor OSK mix, as well as pairwise factors OS, OK, and SK and individual Oct4, Sox2, and KLF4 for their effect on cell trajectories. This study provides a dynamic model for epigenetic changes in aging, differentiation, and reprogramming and highlights barriers and bottlenecks throughout the process.
Epigenome Wide Associations of Smoking Behavior in the Health and Retirement Study
Authors: Fisher Jonah , Mitchell Colter , Meier Helen , Crimmins Eileen , Thyagarajan Bharat , Faul Jessica
Published: December 2021

DNA methylation (DNAm) is an increasingly popular biomarker of health and aging outcomes. Smoking behaviors have a significant and well documented correlation with methylation signatures within the epigenome and are important confounding variables to account for in epigenome-wide association studies (EWAS). However, the common classification of individuals as ‘current’, ‘former’, and ‘never’ smokers may miss crucial DNAm patterns associated with other smoking behaviors such as duration, intensity, and frequency of cigarette smoking, resulting in an underestimation of the contribution of smoking behaviors to DNAm and potentially biasing EWAS results. We investigated associations between multiple smoking behavioral phenotypes (smoking pack years, smoking duration, smoking start age, and smoking end age) and single site DNAm using linear regressions adjusting for age, sex, race/ethnicity, education, and cell-type proportions in a subsample of individuals who participated in the HRS 2016 Venous Blood Study (N=1,775). DNAm was measured using the Infinium Methylation EPIC BeadChip. All 4 phenotypes had significant associations (FDR < 0.05) with many methylation sites (packyears=6859, smoking duration=6572, start age=11374, quit age=773). There was not much overlap in DNAm sites between the full set of models with only 6 overlapping between all 4. However, the phenotypes packyears and smoking duration showed large overlap (N=3782). Results suggest additional smoking phenotypes beyond current/former/never smoker classification should be included in EWAS analyses to appropriately account for the influence of smoking behaviors on DNAm.
Longitudinal course of GDF15 levels before acute hospitalization and death in the general population
Authors: Tavenier Juliette , Andersen Ove , Nehlin Jan O , Petersen Janne
Published: December 2021

Growth differentiation 15 (GDF15) is a potential novel biomarker of biological aging. To separate the effects of chronological age and birth cohort from biological age, longitudinal studies investigating associations of GDF15 levels with adverse health outcomes are needed. We investigated changes in GDF15 levels over 10 years in an age-stratified sample of the general population and their relation to the risk of acute hospitalization and death. Serum levels of GDF15 were measured three times in 5-year intervals in 2176 participants aged 30, 40, 50, or 60 years from the Danish population-based DAN-MONICA cohort. We assessed the association of single and repeated GDF15 measurements with the risk of non-traumatic acute hospitalizations. We tested whether changes in GDF15 levels over 10 years differed according to the frequency of hospitalizations within 2 years, or survival within 20 years, after the last GDF15 measurement. The change in GDF15 levels over time was dependent on age and sex. Higher GDF15 levels and a greater increase in GDF15 levels were associated with an increased risk of acute hospitalization in adjusted Cox regression analyses. Participants with more frequent admissions within 2 years, and those who died within 20 years, after the last GDF15 measurement already had elevated GDF15 levels at baseline and experienced greater increases in GDF15 levels during the study. The change in GDF15 levels was associated with changes in C-reactive protein and biomarkers of kidney, liver, and cardiac function. Monitoring of GDF15 starting in middle-age could be valuable for the prediction of adverse health outcomes.
Metabolic Syndrome and Neurocognitive Function among older Hispanics/Latinos with HIV
Authors: Marquine Maria , Kamalyan Lily , Yassai-Gonzalez David , Cherner Mariana , Ellis Ronald , Umlauf Anya , Jeste Dilip , Heaton Robert
Published: December 2021

Neurocognitive impairment is prevalent among persons with HIV (PWH), particularly among Hispanics/Latinos/as/x (henceforth Hispanics). We examined disparities in HIV-associated neurocognitive function between older Hispanic and non-Hispanic White PWH, and the potential role of metabolic syndrome (MetS) in explaining these disparities. Participants included 116 community-dwelling PWH ages 50-75, who were enrolled in a cohort study in southern California (58 Hispanic [53% Spanish-speaking] and 58 age-comparable non-Hispanic White; Overall group: Age: M=57.9, SD=5.7; Education: M=13, SD=3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy [ART], 4% detectable plasma RNA). A global neurocognition score was derived from T-Scores on a comprehensive neurocognitive battery, with separate demographic adjustments for English and Spanish-speakers. MetS was ascertained via standard criteria that considered central obesity, elevated triglycerides, low high-density lipoprotein cholesterol, and elevated fasting glucose, as well as current medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV-disease characteristics. Hispanics had higher rates of MetS (56%) than non-Hispanic Whites (37%; p<.05). A stepwise regression model on global neurocognition including ethnicity and covariates that differed between ethnic groups, selected only Hispanic ethnicity as a significant predictor (B=-3.82, SE=1.27, p<.01). A comparable model also including MetS showed that both Hispanic ethnicity (B=-3.39, SE=1.31, p=.01) and MetS (B=-2.73, SE=1.31, p=.04), were significantly associated with worse global neurocognition. Findings indicate that MetS does not fully explain disparities in neurocognitive function between Hispanic and non-Hispanic White older PWH, but rather is an independent predictor of neurocognitive function along with Hispanic ethnicity.
Methods used in 'ALDH2*2 association with longevity and reduced risk of cognitive decline in Japanese-American men'
Authors: Sachan Anubhav Nikunj Singh , Edland Steven , Chosy Julia , Launer Lenore , Seshadri Sudha , White Lon
Published: December 2021

ALDH2*2 is a loss of function mutation common in East Asian populations associated with facial flushing on exposure to alcohol and increased risk of certain cancers. Conversely, absence of the ALDH2*2 mutation is associated with increased risk of hypertension and cerebral microbleeds, and two recent studies report a higher frequency of ALDH2*2 alleles in nonagenarians compared to population control samples. We used survival analysis to investigate the association between ALDH2*2 and risk of cognitive impairment and death after controlling for midlife alcohol consumption and other covariates. Participants are 621 Japanese-American men (72 to 92) enrolled in the Honolulu Asia Aging Study (HAAS) and assessed for cognitive impairment for up to 20 years. Impairment was defined as crossing below a threshold score of 74 on the Cognitive Assessment Screening Instrument (CASI). Age at death was determined by Hawaii state death certificate. Ounces of ethyl alcohol consumed per month was assessed by structured interview (number, frequency, and type of beverage) conducted 25 years prior to baseline cognitive assessment. Persons heterozygous for the ALDH2*2 variant have reduced risk of cognitive impairment and reduced risk of death, compared to homozygote non-carriers. Covarying by alcohol exposure had no effect on observed associations. This study replicates previous findings associating ALDH2*2 with longevity, and provides evidence the protective effect extends to cognition. This poster details the statistical analysis carried out to obtain these results.
Living With Early-Onset Dementia in China: Through a Person-Centered Care Lens
Authors: Wang Jing , Ding Ding , Zhao Qianhua
Published: December 2021

We conducted semi-structured interviews with 35 dyads of persons with early-onset dementia (EOD) and their primary informal care partners to explore their dyadic experiences of living EOD in Shanghai, China. Many of them are in their 50s and still need to make familial, financial, and social commitments. They experienced significant disruptions of their "normal" family life and family dynamics, social stigma, and felt marginalized when there was very limited age-appropriate support for them. During COVID-19 pandemic, many persons with EDO and their care partners had decreased social networking opportunities, physical exercises and experienced an increased level of social isolation. The pandemic further complicated their family dynamics, relationships, and communications. Care partners used their strengths to adaptively deal with multiple challenges, cope with the stress, social isolation, and normalize their family life by facilitating collaborative work with persons with EOD.
Claims-Based Network Analysis of Disease Progressions in Complex and Non-Complex Older Adults
Authors: Onglao Peter Nicholas , Janer Ciara , Ventura Maria Eloisa , Bangerter Lauren
Published: December 2021

Older adults are the fastest growing subset of complex patients with high medical, behavioral, and social needs. Understanding differences in disease progression patterns between complex and non-complex older adults is critical for understanding disease risk and tailoring patient-centered interventions. We identified complex patients as those having frequent medical encounters and multiple chronic conditions within the first year of the study period and non-complex patients as the converse. This study compares the disease progression patterns of (a) complex and (b) non-complex older adults by creating disease progression networks (DPN) from claims data of 762,362 patients (mean age = 73) from 2016 to 2020. We characterized the network size and density between the complex patient DPN (C-DPN) and non-complex patient DPN (NC-DPN), and compared disease progression incidence, time-to-progression, and age- and gender-related risk. Results show that the C-DPN was denser and had a wider range of values for risk of progression compared to the NC-DPN. This implies more varied disease progression patterns occurring in the complex adults. We were also able to compare (median) time-to-progressions of diseases relative to each subpopulation and found variation in disease progression time. Furthermore, k-means clustering on the network allowed us to identify highly connected diseases involved in many disease pathways that are prevalent among older adults. (e.g., lipoprotein disorders, hypertension, major depressive disorder). Our results suggest that DPNs can be used to identify important conditions and time-points for tailoring care to the complex and non-complex older adults.