Improved Health Outcomes in Patients with Systemic Lupus Erythematosus Following Early Belimumab Initiation Without Prior Immunosuppressant Use: A Real-World Descriptive Study.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. METHODS: This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May 2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24 months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24 months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. RESULTS: Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9 months; severe baseline SLE, 6.2 vs 11.6 months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24 months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7 months; severe baseline SLE, 22.7 vs 21.6 months). All-cause HCRU was similar between cohorts. CONCLUSIONS: These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

Psychosocial factors associated with 7-year change in cognition among middle-aged and older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) and Sociocultural ancillary studies.

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey-linear regression models examined associations between psychosocial exposures and 7-year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. HIGHLIGHTS: Psychosocial factors are differentially related to cognitive changes in Latinos. Role of culturally relevant factors on cognition should be further explored. Familism predicted decline in global cognition, verbal learning, and memory. Ethnic identity predicted increase in global cognition and memory.

Connections between reproductive health and cognitive aging among women enrolled in the HCHS/SOL and SOL-INCA.

INTRODUCTION: Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women. METHODS: Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence). RESULTS: Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence. DISCUSSION: Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

The Spanish-English bilingual experience and cognitive change in Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging.

INTRODUCTION: Studies suggest bilingualism may delay behavioral manifestations of adverse cognitive aging including Alzheimer's dementia. METHODS: Three thousand nine hundred sixty-three participants (unweighted mean population age ≈56 years) at Hispanic Community Health Study/Study of Latinos baseline (2008-2011) self-reported their and their parents' birth outside the United States, Spanish as their first language, and used Spanish for baseline and comparable cognitive testing 7 years later (2015-2018). Spanish/English language proficiency and patterns of use were self-rated from 1 = only Spanish to 4 = English > Spanish. Cognitive testing included test-specific and global composite score(s) of verbal learning, memory, word fluency, and Digit Symbol Substitution (DSS). Survey linear regression models examined associations between baseline bilingualism scores and cognition. RESULTS: Higher second-language (English) proficiency and use were associated with higher global cognition, fluency, and DSS at follow-up and better than predicted change in fluency. DISCUSSION: The bilingual experience was more consistently related to 7-year level versus change in cognition for Hispanics/Latinos.

Cardiovascular correlates of sleep apnea phenotypes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Identifying Obstructive Sleep Apnea (OSA) phenotypes among middle-aged and older Hispanics/Latinos can facilitate personalized care, better inform treatment decisions, and could lead to improved clinical outcomes. METHODS: We focused on middle-aged and older adults (ages ≥45-74 years at baseline) with an apnea-hypopnea index (AHI) ≥5 from the HCHS/SOL (2008-2011) (unweighted n = 3,545). We used latent class analyses (LCA) to identify empirical and clinically meaningful OSA phenotypes. Sleep variables included AHI, percent sleep time SpO2<90%, Epworth Sleepiness Scale (ESS), Women's Health Initiative Insomnia Rating Scale (WHIIRS) score, self-reported average sleep duration, restless legs symptoms, napping frequency, and self-reported sleep quality. We used survey logistic and Poisson regression to test the associations between our OSA phenotypes and prevalent and incident cardiovascular measures (cardiovascular disease, heart failure, Stroke/TIA, hypertension, diabetes, and the Framingham Cardiovascular Risk Score). RESULTS: Average AHI, ESS, WHIIRS, and sleep duration were 18.1±19.5, 6.3±6.1, 7.4±6.6, and 7.8±1.7 hours, respectively, and 2.9% had zero percent time SpO2 <90%. We identified a three-class solution that clustered individuals into (1) insomnia OSA (44.3%), (2) asymptomatic mild OSA, (36.2%) and (3) symptomatic OSA (19.5%). Elevated WHIIRS and AHI scores primarily drove classification into groups one and three, respectively. In covariate adjusted models, OSA phenotypes were differentially associated with prevalence (baseline and seven years later) and incidence of cardiovascular measures. CONCLUSIONS: OSA subtypes in diverse U.S. Hispanic/Latino adults have different cardiovascular complications. More targeted research, that takes these variations into account, could help ameliorate Hispanic/Latino sleep and cardiovascular health disparities.

Associations Between Midlife Functional Limitations and Self-Reported Health and Cognitive Status: Results from the 1998-2016 Health and Retirement Study.

BACKGROUND: Life-course approaches to identify and help improve modifiable risk factors, particularly in midlife, may mitigate cognitive aging. OBJECTIVE: We examined how midlife self-rated physical functioning and health may predict cognitive health in older age. METHODS: We used data from the Health and Retirement Study (1998-2016; unweighted-N = 4,685). We used survey multinomial logistic regression and latent growth curve models to examine how midlife (age 50-64 years) activities of daily living (ADL), physical function, and self-reported health affect cognitive trajectories and cognitive impairment not dementia (CIND) and dementia status 18 years later. Then, we tested for sex and racial/ethnic modifications. RESULTS: After covariates-adjustment, worse instrumental ADL (IADL) functioning, mobility, and self-reported health were associated with both CIND and dementia. Hispanics were more likely to meet criteria for dementia than non-Hispanic Whites given increasing IADL impairment. CONCLUSION: Midlife health, activities limitations, and difficulties with mobility are predictive of dementia in later life. Hispanics may be more susceptible to dementia in the presence of midlife IADLs. Assessing midlife physical function and general health with brief questionnaires may be useful for predicting cognitive impairment and dementia in later life.

The Association of Stress, Metabolic Syndrome, and Systemic Inflammation With Neurocognitive Function in the Hispanic Community Health Study/Study of Latinos and Its Sociocultural Ancillary Study.

OBJECTIVES: Identifying sociocultural correlates of neurocognitive dysfunction among Hispanics/Latinos, and their underlying biological pathways, is crucial for understanding disparities in Alzheimer's disease and related dementias. We examined cross-sectional associations between stress and neurocognition, and the role that metabolic syndrome (MetS) and systemic inflammation might play in these associations. METHOD: Participants included 3,045 adults aged 45-75 (56% female, education 0-20+ years, 86% Spanish-speaking, 23% U.S.-born), enrolled in the Hispanic Community Health Study/Study of Latinos and its Sociocultural Ancillary Study. Global neurocognition was the primary outcome and operationalized as the average of the z scores of measures of learning and memory, word fluency, and processing speed. Stress measures included self-report assessments of stress appraisal (perceived and acculturative stress) and exposure to chronic and traumatic stressors. MetS was defined via established criteria including waist circumference, high blood pressure, elevated triglycerides, fasting plasma glucose, and high levels of high-density lipoprotein cholesterol. Systemic inflammation was represented by high-sensitivity C-reactive protein (hs-CRP). RESULTS: Separate survey multivariable linear regression models adjusting for covariates showed that higher perceived (b = -0.004, SE = 0.002, p < .05) and acculturative stress (b = -0.004, SE = 0.001, p < .0001) were significantly associated with worse global neurocognition, while lifetime exposure to traumatic stressors was associated with better global neurocognition (b = 0.034, SE = 0.009, p < .001). Neither MetS nor hs-CRP were notable pathways in the association between stress and neurocognition; rather, they were both independently associated with worse neurocognition in models including stress measures (ps < .05). DISCUSSION: These cross-sectional analyses suggest that stress appraisal, MetS, and systemic inflammation may be targets to reduce neurocognitive dysfunction among Hispanics/Latinos.

Modifying pathways by age and sex for the association between combined sleep disordered breathing and long sleep duration with neurocognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

INTRODUCTION: We aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N = 5500) in different age and sex groups. METHODS: The exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (< 6 hours, 6-9 hours, ≥ 9 hours). The outcome was 7-year ND. RESULTS: Mean age was 56.0 years, 54.8% were females. Obesity modified the association between SDB/SD and ND in memory (F = 21.49, P < 0.001) and global cognition (F = 9.14, P < 0.001) in the oldest age group. Women without MetS with combined long sleep/SDB exhibited most pronounced decline in global cognition (F = 3.07, P = 0.010). DISCUSSION: The association between combined SDB/long sleep and declines in memory and global cognition was most pronounced in obese older adults. Among women, MetS status modified the association between long sleep/SDB and decline in global cognition.

Actigraphic sleep patterns and cognitive decline in the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We determined if actigraphy-derived sleep patterns led to 7-year cognitive decline in middle-aged to older Hispanic/Latino adults. METHODS: We examined 1035 adults, 45 to 64 years of age, from the Hispanic Community Health Study/Study of Latinos. Participants had repeated measures of cognitive function 7 years apart, home sleep apnea studies, and 1 week of actigraphy. Survey linear regression evaluated prospective associations between sleep and cognitive change, adjusting for main covariates. RESULTS: Longer sleep-onset latency was associated with declines in global cognitive function, verbal learning, and verbal memory. Longer sleep-onset latency was also cross-sectionally associated with verbal learning, verbal memory, and word fluency. Sleep fragmentation was not associated with cognitive change. CONCLUSION: In a cohort of mostly middle-aged Hispanic/Latinos, actigraphy-derived sleep-onset latency predicted 7-year cognitive change. These findings may serve as targets for sleep interventions of cognitive decline.

Cognition and Daily Functioning: Results from the Hispanic Community Health Study/Study of Latinos (SOL) and Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

BACKGROUND: Among older adults, poorer cognitive functioning has been associated with impairments in instrumental activities of daily living (IADLs). However, IADL impairments among older Hispanics/Latinos is poorly understood. OBJECTIVE: To characterize the relationships between cognition and risk for IADL impairment among diverse Hispanics/Latinos. METHODS: Participants included 6,292 community-dwelling adults from the Study of Latinos - Investigation of Neurocognitive Aging, an ancillary study of 45+ year-olds in the Hispanic Community Health Study/Study of Latinos. Cognitive data (learning, memory, executive functioning, processing speed, and a Global cognitive composite) were collected at Visit 1. IADL functioning was self-reported 7 years later, and treated as a categorical (i.e., risk) and continuous (i.e., degree) measures of impairment. Survey two-part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression tested the associations of cognitive performance (individual tests and composite z-score) with IADL impairment. Additionally, we investigated the moderating role of age, sex, and Hispanic/Latino background on the association between cognition and IADL impairment. RESULTS: Across all cognitive measures, poorer performance was associated with higher odds of IADL impairment 7 years later. Associations were generally stronger for the oldest group (70+ years) relative to the youngest group (50-59 years). Sex and Hispanic/Latino background did not modify the associations. Across the full sample, lower scores on learning, memory, and the Global cognitive composite were also associated with higher degree of IADL impairment. CONCLUSION: Across diverse Hispanics/Latinos, cognitive health is an important predictor of everyday functioning 7 years later, especially in older adulthood.

Sleep and neurocognitive decline in the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: To determine if sleep-disordered breathing (SDB), daytime sleepiness, insomnia, and sleep duration predict seven-year neurocognitive decline in US Hispanics/Latinos (N = 5247). METHODS: The exposures were baseline SDB, daytime sleepiness, insomnia, and sleep duration. The outcomes were change in episodic learning and memory (B-SEVLT-Sum and SEVLT-Recall), language (word fluency [WF]), processing speed (Digit Symbol Substitution), and a cognitive impairment screener (Six-item Screener [SIS]). RESULTS: Mean age was 63 ± 8 years, with 55% of the population being female with 7.0% Central American, 24.5% Cuban, 9.3% Dominican, 35.9% Mexican, 14.4% Puerto Rican, and 5.1% South American background. Long sleep (>9 hours), but not short sleep (<6 hours), was associated with decline (standard deviation units) in episodic learning and memory (ßSEVLT-Sum= -0.22 [se = 0.06]; P < .001; ßSEVLT-Recall = -0.13 [se = 0.06]; P < .05), WF (Pwf = -0.20 [se 5 0.06]; P < .01), and SIS (ßSIS = -0.16 [se = 0.06]; P < .01), but not processing speed, after adjusting for covariates. SDB, sleepiness, and insomnia were not associated with neurocognitive decline. CONCLUSION: Long sleep duration predicted seven-year cognitive decline.