Post-traumatic stress in older, community-dwelling adults with hypertension during the COVID-19 pandemic: An investigation of pre-pandemic sociodemographic, health, and vascular and inflammatory biomarker predictors.

COVID-19 pandemic-related traumatic stress (PRTS) symptoms are reported in various populations, but risk factors in older adults with chronic medical conditions, remain understudied. We therefore examined correlates and pre-pandemic predictors of PRTS in older adults with hypertension during COVID-19. Participants in California, aged 61-92 years (n = 95), participated in a pre-pandemic healthy aging trial and later completed a COVID-19 assessment (May to September 2020). Those experiencing ⩾1 PRTS symptom (n = 40), and those without PRTS symptoms (n = 55), were compared. The PRTS+ group had poorer mental and general health and greater impairment in instrumental activities of daily living. Pre-pandemic biomarkers of vascular inflammation did not predict increased odds of PRTS; however, greater pre-pandemic anxiety and female gender did predict PRTS during COVID-19. Our findings highlight PRTS as a threat to healthy aging in older adults with hypertension; targeted approaches are needed to mitigate this burden, particularly for females and those with pre-existing anxiety.

Tai Chi versus health education as a frailty intervention for community-dwelling older adults with hypertension.

BACKGROUND: Frailty is associated with poor outcomes among older adults with hypertension and complicates its pharmacological management. Here, we assessed whether 12-weeks of instructor-guided, group Tai Chi (TC) practice improved frailty relative to Healthy Aging Practice-centered Education (HAP-E) classes in older adults with hypertension. METHODS: Secondary analysis of a randomized controlled trial in San Diego County, USA, of 167 community-dwelling individuals aged ≥ 60 yrs (70% female; 72.1 ± 7.5 yrs), defined as non-frail (66%) or frail (34%) based on 53-item deficit accumulation frailty index (FI). Linear mixed-effects models were used to assess pre-to-post intervention differences in FI and logistic regression to explore differential odds of clinically meaningful FI change. RESULTS: One hundred thirty-one participants completed post-intervention assessments. Frailty decreased pre-to-post intervention in the TC (ΔFI = - 0.016, d = - 0.39, - 0.75 to - 0.03), but not the HAP-E arm (ΔFI = - 0.009, d = - 0.13, - 0.52-0.27), despite no significant group differences between the TC and HAP-E arms (d = - 0.11, - 0.46-0.23). Furthermore, greater odds of improved FI were observed for frail participants in the TC (OR = 3.84, 1.14-14.9), but not the HAP-E (OR = 1.34, 0.39-4.56) arm. Subgroup analysis indicated treatment effects in TC were attributed to frail participants (frail: ΔFI = - 0.035, d = - 0.68, -1.26 to - 0.08; non-frail: ΔFI = - 0.005, d = - 0.19, - 0.59-0.22), which was not the case in the HAP-E arm (frail: ΔFI = - 0.017, d = - 0.23, - 0.81-0.35; non-frail: ΔFI = - 0.003, d = - 0.07, - 0.47-0.33). Frail participants were no more likely to drop-out of the study than non-frail (71% vs. 69% retained). CONCLUSIONS: Twelve weeks of twice-weekly guided TC practice was well-tolerated, associated with decreases in frailty, and increased odds of clinically meaningful FI improvement at post-intervention.

Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV.

Background: Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex. Methods: Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities. Results: Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C-C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (ß = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (ß = -3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected. Interpretation: We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis.

Tai chi or health education for older adults with hypertension: effects on mental health and psychological resilience to COVID-19.

OBJECTIVE: To compare the effectiveness of 12 weeks of community-based, in-person, group Tai Chi (TC) and Health Education (HAP-E) in improving health and wellbeing in older adults with hypertension and in promoting psychological resilience during COVID-19. METHODS: A 12-week randomized controlled trial (RCT) in San Diego County, USA. Self-reported depressive symptoms, anxiety, sleep disturbances, gratitude, resilience, mental and physical health were assessed in-person pre- and post-intervention, and by long-term follow-up surveys during COVID-19. Linear mixed-effects models were used to assess study arm differences over time and logistic regression to identify predictors of positive intervention response. RESULTS: Of 182 randomized participants (72.6 ± 7.9 yrs; 72% female), 131 completed the intervention. Modest improvements in health and wellbeing occurred post-intervention in both arms (Cohen's d: TC = 0.38, 95% CI: 0.25-0.51; HAP-E = 0.24, 0.11-0.37), though positive intervention responses were more than twice as likely in TC (OR = 2.29, 1.07-4.57). Younger age, higher anxiety, and poorer mental health at baseline predicted greater odds of response. Small declines in health and wellbeing were reported at the first COVID-19 follow-up, with smaller declines in the TC arm (Cohen's d: TC = -0.15, -0.31-0.00; HAP-E = -0.34, -0.49 to -0.19). Health and wellbeing stabilized at the second COVID-19 follow-up. Most participants (>70%) reported that the interventions benefitted their health and wellbeing during COVID-19. CONCLUSION: TC and HAP-E improved health and wellbeing, though TC conferred greater odds of an improved mental health response. Declines in health and wellbeing were observed at pandemic follow-up, with smaller declines in the TC arm, suggesting increased resilience.

Current Challenges and Solutions for Clinical Management and Care of People with HIV: Findings from the 12th Annual International HIV and Aging Workshop.

People with HIV on combination antiretroviral therapy (ART) have longer life expectancy and are increasingly experiencing age-related comorbidities. Thus, aging with HIV has become a central issue in clinical care and research, which has been particularly challenging with the intersection of the ongoing coronavirus (COVID)-19 pandemic. Since 2009, the International Workshop on HIV and Aging has served as a multidisciplinary platform to share research findings from cross-disciplinary fields along with community advocates to address critical issues in HIV and aging. In this article, we summarize the key oral presentations from the 12th Annual International Workshop on HIV and Aging, held virtually on September 23rd and 24th, 2021. The topics ranged from basic science research on biological mechanisms of aging to quality of life and delivery of care under the COVID-19 pandemic. This workshop enriched our understanding of HIV and aging under the COVID-19 pandemic, identified challenges and opportunities to combat the impact of COVID-19 on HIV communities, and also provided updated research and future directions of the field to move HIV and aging research forward, with the ultimate goal of successful aging for older people with HIV.

Anterior Insula Activation During Cardiac Interoception Relates to Depressive Symptom Severity in HIV-Positive and HIV-Negative Postmenopausal Women.

OBJECTIVE: This study aimed to determine whether subclinical symptoms of depression in postmenopausal women are associated with blood oxygen level-dependent (BOLD) activity within the anterior insula during cardiac interoceptive awareness and whether this association differs for persons living with the human immunodeficiency virus (PWH). METHOD: Twenty-three postmenopausal (mean [standard deviation] age = 56.5 [4.8] years) and 27 HIV-negative women (mean [standard deviation] age = 56.4 [8.0]) underwent functional magnetic resonance imaging while performing a heartbeat detection task. BOLD activation within the bilateral anterior insula based on the contrast of a heartbeat detection condition with and without a distracting tone was entered along with age, HIV status, and psychological stress into two multivariate regression models with self-reported depressive symptom severity as the outcome. RESULTS: Depressive symptoms did not vary by HIV status, nor was there a main effect or interaction for PWH on insula BOLD activation. Depressive symptoms were positively associated with psychological stress for the left ( ß = 0.310, t (49) = 2.352, p = .023) and right brain models ( ß = 0.296, t (49) = 2.265, p = .028) as well as the magnitude of BOLD activation in the left insula ( ß = 0.290, t (49) = 2.218, p = .032) and right insula ( ß = 0.318, t (49) = 2.453, p = .018), respectively. Exploratory analyses revealed that greater magnitude of BOLD activation attributed to exteroceptive noise (tone) was also correlated with self-reported distrust and preoccupation with interoceptive sensations. CONCLUSIONS: Results support an active interference model for interoceptive awareness wherein greater BOLD signal in the anterior insula in the presence of distracting exteroceptive stimuli may reflect greater prediction error, a feature of depression.

Cognitive and Physiologic Reserve Independently Relate to Superior Neurocognitive Abilities in Adults Aging With HIV.

BACKGROUND: To investigate joint contributions of cognitive and physiologic reserve to neurocognitive SuperAging in older persons with HIV (PWH). METHODS: Participants included 396 older PWH (age range: 50-69 years) who completed cross-sectional neuropsychological and neuromedical evaluations. Using published criteria, participants exhibiting global neurocognition within normative expectations of healthy 25-year-olds were classified as SuperAgers (SA; n = 57). Cognitively normal (CN; n = 172) and impaired (n = 167) participants were classified with chronological age-based norms. Cognitive reserve was operationalized with an estimate of premorbid verbal intelligence, and physiologic reserve was operationalized with a cumulative index of 39 general and HIV-specific health variables. Analysis of variance with confirmatory multinomial logistic regression examined linear and quadratic effects of cognitive and physiologic reserve on SA status, adjusting for chronological age, depression, and race/ethnicity. RESULTS: Univariably, SA exhibited significantly higher cognitive and physiologic reserve compared with CN and cognitively impaired ( d s ≥ 0.38, p s < 0.05). Both reserve factors independently predicted SA status in multinomial logistic regression; higher physiologic reserve predicted linear increases in odds of SA, and higher cognitive reserve predicted a quadratic "J-shaped" change in odds of SA compared with CN (ie, odds of SA > CN only above 35th percentile of cognitive reserve). CONCLUSIONS: Each reserve factor uniquely related to SA status, which supports the construct validity of our SA criteria and suggests cognitive and physiologic reserve reflect nonoverlapping pathways of neuroprotection in HIV. Incorporation of proxy markers of reserve in clinical practice may improve characterization of age-related cognitive risk and resilience among older PWH, even among PWH without overt neurocognitive impairment.

Learning to forget: Hippocampal-amygdala connectivity partially mediates the effect of sexual trauma severity on verbal recall in older women undiagnosed with posttraumatic stress disorder.

Verbal learning deficits are common among sexually traumatized women who have not been formally diagnosed with posttraumatic stress disorder (PTSD). Aberrant resting-state functional connectivity (rsFC) of the amygdala and hippocampus are implicated in PTSD and verbal memory impairment. We tested rsFC between bilateral dentate gyrus (DG) and both centromedial (CM) and basolateral (BL) nuclei of the amygdala as statistical mediators for the effect of sexual trauma-related symptom severity on delayed verbal recall performance in 63 older women (age: 60-85 years) undiagnosed with PTSD. Participant data were drawn from the NKI-Rockland Study. Individuals completed a 10-min resting-state scan, Rey Auditory Verbal Learning Test (RAVLT), and the Sexual Abuse Trauma Index (SATI) from the Trauma Symptom Checklist. Z-scores indicating rsFC of DG with BL and CM amygdala seeds were evaluated in two separate mediation models. Higher SATI scores were associated with lower RAVLT after controlling for age, ß = -.23, 95% CI [.48, .03], p = .039. This effect was negated upon adding a negative path from SATI to rsFC of left DG and right CM, ß = -.29, 95% CI [-.52, -.02], p = .022, and a positive path from that seed pair to RAVLT List A recall, ß = .28, 95% CI [.03, 0.48], p = .015. Chi-square fit indices supported partial mediation by this seed pair, p = .762. In the absence of PTSD sexual trauma symptoms partially relate to verbal learning deficits as a function of aberrant rsFC between left hippocampus DG and right amygdala CM nuclei.

CSF markers of AD-related pathology relate specifically to memory impairment in older people with HIV: a pilot study.

Given the co-occurrence of memory impairment in HIV-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment/Alzheimer's disease (aMCI/AD), biomarkers are needed that can disentangle these conditions among people with HIV (PWH). We assessed whether cerebrospinal fluid (CSF) markers of AD could help in this effort by determining their relationship to learning and memory deficits versus cognitive deficits more characteristic of HAND than aMCI/AD (processing speed and complex visual/motor coordination) among 31 older PWH. CSF amyloid-ß42 phosphorylated-tau, amyloid-ß40/amyloid-ß42 and phosphorylated-tau/amyloid-ß42 ratio related to learning/memory performance but not HAND-related deficits, suggesting that these biomarkers may have utility in disentangling aMCI/AD from HAND.

Identification of Youthful Neurocognitive Trajectories in Adults Aging with HIV: A Latent Growth Mixture Model.

Despite the neurocognitive risks of aging with HIV, initial cross-sectional data suggest a subpopulation of older people with HIV (PWH) possess youthful neurocognition (NC) characteristic of SuperAgers (SA). Here we characterize longitudinal NC trajectories of older PWH and their convergent validity with baseline SA status, per established SuperAging criteria in PWH, and baseline biopsychosocial factors. Growth mixture modeling (GMM) identified longitudinal NC classes in 184 older (age ≥ 50-years) PWH with 1-5 years of follow-up. Classes were defined using 'peak-age' global T-scores, which compare performance to a normative sample of 25-year-olds. 3-classes were identified: Class 1Stable Elite (n = 31 [16.8%], high baseline peak-age T-scores with flat trajectory); Class 2Quadratic Average (n = 100 [54.3%], intermediate baseline peak-age T-scores with u-shaped trajectory); Class 3Quadratic Low (n = 53 [28.8%], low baseline peak-age T-scores with u-shaped trajectory). Baseline predictors of Class 1Stable Elite included SA status, younger age, higher cognitive and physiologic reserve, and fewer subjective cognitive difficulties. This GMM analysis supports the construct validity of SuperAging in older PWH through identification of a subgroup with longitudinally-stable, youthful neurocognition and robust biopsychosocial health.

RESUMEN: A pesar de los riesgos neurocognitivos de envejecer con VIH, datos transversales iniciales sugieren que una subpoblación de personas con VIH (PCV) de edad mayor posee neurocognición (NC) juvenil, característica de los Súper-Ancianos (SA). Aquí nosotros caracterizamos trayectorias longitudinales de NC en PCV mayores y su validez convergente con su status de referencia de SA, según los criterios establecidos en PCV, y factores biopsicosociales en la base de referencia. El modelo de mezclas Gaussianas (GMM) identificó clases longitudinales de NC en 184 PCV mayores (edad ≥ 50-años) con 1­5 años de seguimiento. Las clases fueron definidas utilizando puntuaciones-T (T-scores) globales de "edad pico", que comparan el desempeño con una muestra normativa de personas de 25 años de edad. 3-clases fueron identificadas: Clase 1Élite Estable (n = 31 [16.8%], puntuaciones-T de edad pico de referencia altas con trayectoria plana; Clase 2Promedio Cuadrático (n = 100 [54.3%], puntuaciones-T de edad pico de referencia intermedias con trayectoria en forma de u); Clase 3Cuadrática Baja (n = 53 [28.8%], %], puntuaciones-T de edad pico de referencia bajas con trayectoria en forma de u). Los predictores de referencia de la Clase 1Élite Estable incluyen estatus de SA, edad mas joven, reserva cognitiva y fisiológica superior, y menos dificultades cognitivas subjetivas. Este análisis GMM apoya la validez del constructo de Súper-Envejecimiento en PCV mayores mediante la identificación de un subgrupo longitudinalmente estable, neurocognición juvenil y una robusta salud biopsicosocial.

Association of cardiometabolic health factors with age-related executive function and episodic memory.

Although decline of cognitive abilities in late life is regarded as a common facet of aging, there is inter-individual variability in this decline. Possible contributors are cardiometabolic risk factors associated with cerebrovascular dysfunction, but a dearth in unifying health-cognition models confound exactly how these risk factors mediate age-related changes in executive function (EF) and episodic memory. This study investigated the indirect effect of age on these cognitive abilities via cardiometabolic risk factors using a structural equation modeling approach. Participants included 738 adults (64% female) ranging from 21 to 85 years of age (M = 47.47, SD = 18.28). An exploratory factor analysis was applied to an EF battery yielding a two-factor solution, consisting of inhibition and cognitive flexibility, that showed acceptable fit (χ2(48) = 101.84, p < .001, CFI = .980, RMSEA = .039, SRMR = .035). The EF latent factors were then included in a confirmatory factor analysis exploring the indirect role of age on episodic memory and EF via blood pressure, cholesterol, triglycerides and body mass index. The theoretical model demonstrated acceptable fit, χ2(108) = 204.071, p < .001, CFI = .972, RMSEA = .035, SRMR = .035. Blood pressure was associated with lower cognitive flexibility (ß = -.20, p < .001) and there was a significant indirect effect of age on episodic memory through cognitive flexibility (ß = .07, p = .021). Results support the "Executive Decline Hypothesis" of age-related episodic memory decline and specifically implicate lower blood pressure control and cognitive flexibility in these changes.

Brainstem network connectivity with mid-anterior insula predicts lower systolic blood pressure at rest in older adults with hypertension.

Central regulation of heart rate and blood pressure provides the bases for a neurogenic mechanism of hypertension (HTN). Post menopause (PM) age coincides with changes in resting state functional brain connectivity (rsFC) as well as increased risk for HTN. Whether the neural networks underpinning cardioautonomic control differ between PM women with and without HTN is unclear. Phenotypic and functional neuroimaging data from the Nathan Kline Institute was first evaluated for group differences in intrinsic network connectivity between 22 HTN post menopausal women and 22 normotensive controls. Intrinsic rsFC of the midbrain-brainstem-cerebellar network with bilateral mid-anterior insula was lower in women with HTN (FWE-corrected, p < 0.05). Z-scores indicating rsFC of these regions were extracted from the 44 PM women and a cohort of 111 adults, not presenting with metabolic or neurodegenerative disease, and compared to in-office systolic and diastolic blood pressure. Lower rsFC of the left (r  = -0.17, p = 0.019) and right (r  = -0.14, p = 0.048) mid-anterior insula with brainstem nuclei was associated with higher systolic blood pressure in the combined sample. The magnitude of this effect in men and women of post menopausal age supports a neurogenic mechanism for blood pressure regulation in older adults with HTN.

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV.

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.

Current assessment of heart rate variability and QTc interval length in HIV/AIDS.

PURPOSE OF REVIEW: The increasing prevalence of cardiovascular disease comorbidity in persons infected with the HIV has become a global concern. The electrocardiogram (ECG) is increasingly being utilized to provide clinically relevant information regarding cardiac arrhythmias and cardio-autonomic dysfunction. The purpose of this review is to summarize the latest research comparing QT and R-to-R interval length as a function of HIV+ status or antiretroviral therapy (ART) regimen. RECENT FINDINGS: Prolongation of the corrected QTc interval may be acquired in HIV+ ART-naive individuals, exacerbated by various classes of ART drugs, and is generally predictive of lethal cardiac arrhythmias, with effects observed from childhood to adulthood. Recent literature also suggests the trend of lower heart rate variability in HIV is indicative of cardiorespiratory and inflammatory-immune dysfunction. SUMMARY: These emergent studies support the clinical relevance of the ECG across the age and HIV disease spectrum. Furthermore, the reported findings have implications for the management of cardiovascular and chronic inflammatory disease comorbidity in persons living with HIV.