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This article proposes a distance‐based framework incentivized by the paradigm shift toward feature aggregation for high‐dimensional data, which does not rely on the sparse‐feature assumption or the permutation‐based inference. Focusing on distance‐based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high‐dimensional variables using pairwise outcomes of between‐subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U‐statistics‐based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root‐n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands. [ABSTRACT FROM AUTHOR]

BackgroundAs of March 2021, in the USA, the COVID-19 pandemic has resulted in over 500,000 deaths, with a majority being people over 65 years of age. Since the start of the pandemic in March 2020, preventive measures, including lockdowns, social isolation, quarantine, and social distancing, have been implemented to reduce viral spread. These measures, while effective for risk prevention, may contribute to increased social isolation and loneliness among older adults and negatively impact their mental and physical health. ObjectiveThis study aimed to assess the impact of the COVID-19 pandemic and the resulting “Stay-at-Home” order on the mental and physical health of older adults and to explore ways to safely increase social connectedness among them. MethodsThis qualitative study involved older adults living in a Continued Care Senior Housing Community (CCSHC) in southern California, USA. Four 90-minute focus groups were convened using the Zoom Video Communications platform during May 2020, involving 21 CCSHC residents. Participants were asked to describe how they were managing during the “stay-at-home” mandate that was implemented in March 2020, including its impact on their physical and mental health. Transcripts of each focus group were analyzed using qualitative methods. ResultsFour themes emerged from the qualitative data: (1) impact of the quarantine on health and well-being, (2) communication innovation and technology use, (3) effective ways of coping with the quarantine, and (4) improving access to technology and training. Participants reported a threat to their mental and physical health directly tied to the quarantine and exacerbated by social isolation and decreased physical activity. Technology was identified as a lifeline for many who are socially isolated from their friends and family. ConclusionsOur study findings suggest that technology access, connectivity, and literacy are potential game-changers to supporting the mental and physical health of older adults and must be prioritized for future research.

BackgroundHeart rate variability (HRV), or variation in beat-to-beat intervals of the heart, is a quantitative measure of autonomic regulation of the cardiovascular system. Low HRV derived from electrocardiogram (ECG) recordings is reported to be related to physical frailty in older adults. Recent advances in wearable technology offer opportunities to more easily integrate monitoring of HRV into regular clinical geriatric health assessments. However, signals obtained from ECG versus wearable photoplethysmography (PPG) devices are different, and a critical first step preceding their widespread use is to determine whether HRV metrics derived from PPG devices also relate to older adults’ physical function. ObjectiveThis study aimed to investigate associations between HRV measured with a wrist-worn PPG device, the Empatica E4 sensor, and validated clinical measures of both objective and self-reported physical function in a cohort of older adults living independently within a continuing care senior housing community. Our primary hypothesis was that lower HRV would be associated with lower physical function. In addition, we expected that HRV would explain a significant proportion of variance in measures of physical health status. MethodsWe evaluated 77 participants from an ongoing study of older adults aged between 65 and 95 years. The assessments encompassed a thorough examination of domains typically included in a geriatric health evaluation. We collected HRV data with the Empatica E4 device and examined bivariate correlations between HRV quantified with the triangular index (HRV TI) and 3 widely used and validated measures of physical functioning—the Short Physical Performance Battery (SPPB), Timed Up and Go (TUG), and Medical Outcomes Study Short Form 36 (SF-36) physical composite scores. We further investigated the additional predictive power of HRV TI on physical health status, as characterized by SF-36 physical composite scores and Cumulative Illness Rating Scale for Geriatrics (CIRS-G) scores, using generalized estimating equation regression analyses with backward elimination. ResultsWe observed significant associations of HRV TI with SPPB (n=52; Spearman ρ=0.41; P=.003), TUG (n=51; ρ=−0.40; P=.004), SF-36 physical composite scores (n=49; ρ=0.37; P=.009), and CIRS-G scores (n=52, ρ=−0.43; P=.001). In addition, the HRV TI explained a significant proportion of variance in SF-36 physical composite scores (R2=0.28 vs 0.11 without HRV) and CIRS-G scores (R2=0.33 vs 0.17 without HRV). ConclusionsThe HRV TI measured with a relatively novel wrist-worn PPG device was related to both objective (SPPB and TUG) and self-reported (SF-36 physical composite) measures of physical function. In addition, the HRV TI explained additional variance in self-reported physical function and cumulative illness severity beyond traditionally measured aspects of physical health. Future steps include longitudinal tracking of changes in both HRV and physical function, which will add important insights regarding the predictive value of HRV as a biomarker of physical health in older adults.

To investigate whether latent subgroups with distinct patterns of factors associated with self-rated successful aging can be identified in community-dwelling adults, and how such patterns obtained from analysis of quantitative data are associated with lay perspectives on successful aging obtained from qualitative responses. Cross-sectional data were collected from 1,510 community-dwelling Americans aged 21–99 years. Latent class regression was used to identify subgroups that explained the associations of self-rated successful aging with measures of physical, cognitive, and mental health as well as psychological measures related to resilience and wisdom. Natural language processing was used to extract important themes from qualitative responses to open-ended questions, including the participants' definitions of successful aging. Two latent subgroups were identified, and their main difference was that the wisdom scale was positively associated with self-rated successful aging in only one subgroup. This subgroup had significantly lower self-rated successful aging and worse scores for all health and psychological measures. In the subgroup's qualitative responses, the theme of wisdom was only mentioned by 10.6%; this proportion was not statistically different from the other subgroup, for which the wisdom scale was not statistically associated with the self-rated successful aging. Our results showed heterogeneous patterns in the factors underpinning successful aging even in community-dwelling adults. We found the existence of a latent subgroup with lower self-rated successful aging as well as worse health and psychological scores, and we suggest a potential role of wisdom in promoting successful aging for this subgroup, even though individuals may not explicitly recognize wisdom as important for successful aging. [ABSTRACT FROM AUTHOR]

Objective: Older adults are vulnerable to perceived stress and loneliness, exacerbated by the COVID-19 pandemic. We previously reported inverse relationships between loneliness/perceived stress and wisdom/resilience. There are few evidence-based tele-health interventions for older adults. We tested a new remotely-administered manualized resilience- and wisdom-focused behavioral intervention to reduce perceived stress and loneliness in older adults.Methods: This pilot controlled clinical trial used a multiple-phase-change single-case experimental design, with three successive 6-week phases: control, intervention, and follow-up periods. The intervention included six once-a-week one-hour sessions. Participants were 20 adults >65 years, without dementia.Results: All 20 participants completed every session. The study indicated feasibility and acceptability of the intervention. While the sample was too small for demonstrating efficacy, there was a reduction (small-to-medium effect size) in perceived stress and loneliness, and increase in resilience, happiness, and components of wisdom and positive perceptions of aging.Conclusion: These preliminary data support feasibility, acceptability, and possible efficacy of a remotely-administered resilience- and wisdom-focused intervention in older adults to reduce stress and loneliness. [ABSTRACT FROM AUTHOR]

Objective: Poor sleep quality is related to worse neurocognition in older adults and in people with HIV (PWH); however, many previous studies have relied only on self-report sleep questionnaires, which are inconsistently correlated with objective sleep measures. We examined relationships between objective and subjective sleep quality and neurocognition in persons with and without HIV, aged 50 and older. Method: Eighty-five adults (PWH n = 52, HIV-negative n = 32) completed comprehensive neuropsychological testing to assess global and domain-specific neurocognition. Objective sleep quality was assessed with wrist actigraphy (total sleep time, efficiency, sleep fragmentation) for five to 14 nights. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index. Results: Objective and subjective sleep measures were unrelated (p's > 0.30). Compared to HIV-negative participants, PWH had greater sleep efficiency (80% vs. 75%, p = 0.05) and were more likely to be using prescription and/or over the counter sleep medication (p = 0.04). In the whole sample, better sleep efficiency (p < 0.01) and greater total sleep time (p = 0.05) were associated with better learning. Less sleep fragmentation was associated with better learning (p < 0.01) and recall (p = 0.04). While PWH had slightly stronger relationships between total sleep time and sleep fragmentation, it is not clear if these differences are clinically meaningful. Better subjective sleep quality was associated with better executive function (p < 0.01) and working memory (p = 0.05); this relationship was primarily driven by the HIV-negative group. Conclusions: Objective sleep quality was associated with learning and recall whereas subjective sleep quality was associated with executive function and working memory. Therefore, assessing objective and subjective sleep quality could be clinically useful, as they are both related to important domains of cognition frequently impacted in HIV-associated neurocognitive disorders as well as neurodegenerative disorders associated with aging. Future studies should evaluate if behavioral sleep interventions can improve neurocognition. [ABSTRACT FROM AUTHOR]

Objectives: Wisdom is a personality trait comprising seven components: self-reflection, pro-social behaviors, emotional regulation, acceptance of diverse perspectives, decisiveness, social advising, and spirituality. Wisdom, a potentially modifiable trait, is strongly associated with well-being. We have published a validated 28-item San Diego Wisdom Scale, the SD-WISE-28. Brief scales are necessary for use in large population-based studies and in clinical practice. The present study aimed to create an abbreviated 7-item version of the SD-WISE. Method: Participants included 2093 people, aged 20-82 years, recruited and surveyed through the online crowdsourcing platform Amazon Mechanical Turk. The participants' mean age was 46 years, with 55% women. Participants completed the SD-WISE-28 as well as validation scales for various positive and negative constructs. Psychometric analyses (factor analysis and item response theory) were used to select one item from each of the seven SD-WISE-28 subscales. Results: We selected a combination of items that produced acceptable unidimensional model fit and good reliability (ω = 0.74). Item statistics suggested that all seven items were strong indicators of wisdom, although the association was weakest for spirituality. Analyses indicated that the 28-item and 7-item SD-WISE are both very highly correlated (r = 0.92) and produce a nearly identical pattern of correlations with demographic and validity variables. Conclusion: The SD-WISE-7, and its derived Jeste-Thomas Wisdom Index (JTWI) score, balances reliability and brevity for research applications. [ABSTRACT FROM AUTHOR]

Objective: To establish whether positive affect (PA) is uniquely associated with loneliness and other social functioning variables beyond negative affect (NA) among older adults.Methods: Four hundred and twenty-eight participants (aged 60+ years old, 82% White, and 48% female) were recruited using random digit-dialing and completed scales for loneliness (UCLA Loneliness Scale), companionship (PROMIS scale), satisfaction with discretionary social activities (PROMIS scale), PA (Center for Epidemiologic Studies [CES] Happiness Scale), and NA (CES-Depression scale and Brief Symptom Inventory-Anxiety Subscale).Results: Multiple linear regression models found PA to be a significant predictor of lower loneliness where the effect of PA on loneliness is dependent on the level of NA; a large effect size at the mean level of NA, which becomes attenuated when NA increases. Although the direction of effect of PA on loneliness will change for NA > 5.10, which is 5 standard deviations away from 0, based on the model estimates, the percent of subjects with this large NA levels is practically 0. Thus, higher PA is associated with lower loneliness, however this effect is attenuated for larger NA. Similarly, multiple linear regression models found that companionship was associated with PA and NA where the effect of PA is dependent on the level of NA; a medium effect size at the mean level of NA, which becomes attenuated when NA increases. As in the case of loneliness, the direction of effect of PA on companionship will change for NA > 3.52, which is 3.5 standard deviation away from 0, based on the model estimates, but the percent of subjects with this large NA levels is practically 0. Thus, higher PA is associated with increased companionship, aand this effect is attenuated with greater NA. Satisfaction with social activities was associated with PA only (medium effect size).Conclusion: Results suggest PA appears to be uniquely associated with social functioning among older adults. These findings support the potential for treatments that target PA to decrease loneliness among older adults, or vice versa. [ABSTRACT FROM AUTHOR]

Background: With the aging of populations worldwide, early detection of cognitive impairments has become a research and clinical priority, particularly to enable preventive intervention for dementia. Automated analysis of the drawing process has been studied as a promising means for lightweight, self-administered cognitive assessment. However, this approach has not been sufficiently tested for its applicability across populations. Objective: The aim of this study was to evaluate the applicability of automated analysis of the drawing process for estimating global cognition in community-dwelling older adults across populations in different nations. Methods: We collected drawing data with a digital tablet, along with Montreal Cognitive Assessment (MoCA) scores for assessment of global cognition, from 92 community-dwelling older adults in the United States and Japan. We automatically extracted 6 drawing features that characterize the drawing process in terms of the drawing speed, pauses between drawings, pen pressure, and pen inclinations. We then investigated the association between the drawing features and MoCA scores through correlation and machine learning–based regression analyses. Results: We found that, with low MoCA scores, there tended to be higher variability in the drawing speed, a higher pause:drawing duration ratio, and lower variability in the pen’s horizontal inclination in both the US and Japan data sets. A machine learning model that used drawing features to estimate MoCA scores demonstrated its capability to generalize from the US dataset to the Japan dataset (R²=0.35; permutation test, P<.001). Conclusions: This study presents initial empirical evidence of the capability of automated analysis of the drawing process as an estimator of global cognition that is applicable across populations. Our results suggest that such automated analysis may enable the development of a practical tool for international use in self-administered, automated cognitive assessment. [ABSTRACT FROM AUTHOR]

Background: Racemic (R,S)‐ketamine is a glutamatergic drug with potent and rapid acting antidepressant effects. An intranasal formulation of (S)‐ketamine was recently approved by the US Food and Drug Administration (FDA) to be used in individuals with treatment‐resistant depression (TRD). There are no data directly comparing outcomes on depression or other comorbidities between these two formulations of ketamine. However, recent meta‐analyses have suggested that IV racemic ketamine may be more potent than IN‐(S)‐ketamine. Methods: We retrospectively analyzed clinical outcomes in 15 Veterans with comorbid TRD and post‐traumatic stress disorder (PTSD) who underwent ketamine treatment at the VA San Diego Neuromodulation Clinic. All Veterans included in this analysis were given at least 6 intranasal (IN)‐(S)‐ketamine treatments prior to switching to treatment with IV racemic ketamine. Results: Veterans receiving ketamine treatment (across both IN‐(S)‐ketamine and IV‐(R,S)‐ketamine) showed significant reductions in both the Patient Health Questionnaire‐9 (PHQ‐9), a self‐report scale measuring depression symptoms (rm ANOVA F(14,42) = 12.6, p < 0.0001), and in the PTSD checklist for DSM‐5 (PCL‐5), a self‐report scale measuring PSTD symptoms (rm ANOVA F(13,39) = 5.9, p = 0.006). Post hoc testing revealed that PHQ‐9 scores were reduced by an average of 2.4 ± 1.2 compared to baseline after (S)‐ketamine treatments (p = 0.1) and by an average of 5.6 ± 1 after IV‐ketamine treatments (p = 0.0003) compared to pretreatment baseline scores. PCL‐5 scores were reduced by an average of 4.3 ± 3.3 after IN (S)‐ketamine treatments (p = 0.6) and 11.8 ± 3.5 after IV‐ketamine treatments (p = 0.03) compared to pretreatment baseline scores. Conclusions: This work suggests that off‐label IV‐(R,S)‐ketamine could be considered a reasonable next step in patients who do not respond adequately to the FDA‐approved IN‐(S)‐ketamine. Further double‐blinded, randomized controlled trials are warranted to assess whether IV racemic ketamine is more effective than IN‐(S)‐ketamine. [ABSTRACT FROM AUTHOR]

Wisdom is a multi-component trait that is important for mental health and well-being. In this study, we sought to understand gender differences in relative strengths in wisdom. A total of 659 individuals aged 27–103 years completed surveys including the 3-Dimensional Wisdom Scale (3D-WS) and the San Diego Wisdom Scale (SD-WISE). Analyses assessed gender differences in wisdom and gender's moderating effect on the relationship between wisdom and associated constructs including depression, loneliness, well-being, optimism, and resilience. Women scored higher on average on the 3D-WS but not on the SD-WISE. Women scored higher on compassion-related domains and on SD-WISE Self-Reflection. Men scored higher on cognitive-related domains and on SD-WISE Emotion Regulation. There was no impact of gender on the relationships between wisdom and associated constructs. Women and men have different relative strengths in wisdom, likely driven by sociocultural and biological factors. Tailoring wisdom interventions to individuals based on their profiles is an important next step. [ABSTRACT FROM AUTHOR]

There has been growing research interest in loneliness and wisdom in recent decades, but no cross-cultural comparisons of these constructs using standardized rating measures in older adults, especially the oldest-old. This was a cross-sectional study of loneliness and wisdom comparing middle-aged and oldest-old adults in Cilento, Italy and San Diego, United States. We examined loneliness and wisdom, using the UCLA Loneliness Scale Version 3 (UCLA-3) and San Diego Wisdom Scale (SD-WISE), respectively, in four subject groups: adults aged 50-65 and those ≥90 years from Cilento, Italy (N = 212 and 47, respectively) and San Diego, California, USA (N = 138 and 85, respectively). After controlling for education, there were no significant group differences in levels of loneliness, while on SD-WISE the Cilento ≥90 group had lower scores compared to the other three groups. There was a strong inverse correlation between loneliness and wisdom in each of the four subject groups. Loneliness was negatively associated while wisdom was positively associated with general health, sleep quality, and happiness in most groups, with varying levels of significance. These results largely support cross-cultural validity of the constructs of loneliness and wisdom, and extend previous findings of strong inverse correlations between these two entities. Loneliness has become a growing public health problem, and the results of our study suggest that wisdom could be a protective factor against loneliness, although alternative explanations are also possible. Research on interventions to reduce loneliness by enhancing wisdom in older adults is needed. [ABSTRACT FROM AUTHOR]

In conclusion, the Zhang et al. (2021) study and the diverse cohort of older Chinese study participants provide an important contribution to the growing knowledge regarding sleep duration and cognitive impairment. The World Health Organization projects the total number of people with dementia worldwide to reach 82 million in 2030, nearly doubling to 152 million by 2050 (Jia, 2020). The current study noted that among individuals with primary and above education, excessive sleep duration was linked to cognitive impairment (Zhang et al., 2021). Zhang and colleagues' (2021) article in the current issue examined links between sleep and cognitive impairment among 3,692 community-dwelling older Chinese participants from a 3-year longitudinal study. [Extracted from the article]

Introduction The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. Materials and Methods Participants (N  = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t -tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. Results Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P  = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P  < 0.001) and were more likely to be male (X 2 [1, N  = 110] = 62.39, P  < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P  = 0.012, d  = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. Conclusions Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans. [ABSTRACT FROM AUTHOR]