Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.

Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Access to Preventive Services for Working-Age Adults With Physical Limitations.

OBJECTIVE: To examine differences in access to preventive services for working-age adults with physical limitations, nonphysical limitations, and no limitations. DESIGN: Observational data were pooled across calendar years 2003 through 2012 from the Medical Expenditure Panel Survey (MEPS), a nationally representative survey of noninstitutionalized U.S. adults. SETTING: Community. PARTICIPANTS: Working-age adults (N=75,145; age range, 18-64y) who responded to all 5 rounds of the MEPS during 2003 through 2012. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Blood pressure checks, flu shots, and dental visits, in the last 12 months. RESULTS: Multivariate analyses showed that adults with physical limitations were more likely to receive a blood pressure check (92.2% vs 69.6%, respectively; P<.001) or flu shot (39.7% vs 23.4%, respectively; P<.001) than adults with no limitations. However, those with physical limitations were less likely to have a dental checkup (44.7% vs 59.4%, respectively; P<.001) than those with no limitation. Having a usual source of care increased the odds of receiving preventive services. CONCLUSIONS: The study has implications for providers and policymakers. Policies that support the adequacy of provider networks and continuity with a usual source of care may increase the use of preventive services in adults with physical limitations.

Viral microRNA effects on pathogenesis of polyomavirus SV40 infections in syrian golden hamsters.

Effects of polyomavirus SV40 microRNA on pathogenesis of viral infections in vivo are not known. Syrian golden hamsters are the small animal model for studies of SV40. We report here effects of SV40 microRNA and influence of the structure of the regulatory region on dynamics of SV40 DNA levels in vivo. Outbred young adult hamsters were inoculated by the intracardiac route with 1×107 plaque-forming units of four different variants of SV40. Infected animals were sacrificed from 3 to 270 days postinfection and viral DNA loads in different tissues determined by quantitative real-time polymerase chain reaction assays. All SV40 strains displayed frequent establishment of persistent infections and slow viral clearance. SV40 had a broad tissue tropism, with infected tissues including liver, kidney, spleen, lung, and brain. Liver and kidney contained higher viral DNA loads than other tissues; kidneys were the preferred site for long-term persistent infection although detectable virus was also retained in livers. Expression of SV40 microRNA was demonstrated in wild-type SV40-infected tissues. MicroRNA-negative mutant viruses consistently produced higher viral DNA loads than wild-type SV40 in both liver and kidney. Viruses with complex regulatory regions displayed modestly higher viral DNA loads in the kidney than those with simple regulatory regions. Early viral transcripts were detected at higher levels than late transcripts in liver and kidney. Infectious virus was detected infrequently. There was limited evidence of increased clearance of microRNA-deficient viruses. Wild-type and microRNA-negative mutants of SV40 showed similar rates of transformation of mouse cells in vitro and tumor induction in weanling hamsters in vivo. This report identified broad tissue tropism for SV40 in vivo in hamsters and provides the first evidence of expression and function of SV40 microRNA in vivo. Viral microRNA dampened viral DNA levels in tissues infected by SV40 strains with simple or complex regulatory regions.

Downstream tests, treatments, and annual direct payments in older men cared for by primary care providers with high or low prostate-specific antigen screening rates using 100 percent Texas U.S. Medicare public insurance claims data: a retrospective cohort study.

BACKGROUND: All authorities recommend against prostate specific antigen (PSA) screening in men 75 years and older. However, some primary care physicians (PCPs) continue to have high rates of PSA, with large variation in testing. We assessed the tests, treatments, and payments for prostate cancer care in men aged 75 or older who have PCPs with high or low PSA testing rates. METHODS: We performed a retrospective cohort study using the 2010 Medicare beneficiaries aged 75 or older in Texas, United States who had no prostate cancer in 2007-2009 and had an identifiable PCP. We first identified high vs. low PSA testing PCPs, and then grouped older men in the two PCP groups. We determined health care visits to any provider and to urologists in office and outpatient settings. We estimated the direct medical payments for prostate cancer care for diagnostics, treatments and visits to providers in 2010-2011 using the generalized gamma model with log link function. RESULTS: In multilevel, multivariable analyses, 25.4% (n = 550) of PCPs had PSA testing rates in men aged 75 or older that were significantly higher than the mean rate of all 2,169 Texas PCPs; 29.4% (n = 638) had rates that were significantly lower. In all, 22,853 vs. 23,929 older men were cared for by PCPs with high vs. low testing rates. Older men cared for by high PSA rate PCPs were more likely to receive a PSA test (OR 3.64, 95% CI 3.48-3.80), a biopsy (OR 1.16, 95% CI 1.02-1.31), an ultrasound (OR 1.19, 95% CI 1.07-1.32) or any radiation treatment (OR 1.31, 95% CI 1.03-1.66) than men cared for by low PSA rate PCPs. Men with high PSA rate PCPs were 1.21 (95% CI 1.05-1.39) times more likely to have such outpatient visits. The average annual adjusted Medicare payments for prostate cancer care was $25.60 higher for patients cared for by PCPs with high PSA test rates. CONCLUSIONS: Older men seeing PCPs with high rates of PSA testing undergo more testing and treatments for prostate cancer, with higher Medicare insurance payments. Future studies are needed to delineate whether men seeing PCPs with low testing rates likely received PSA tests from other providers.

Social Determinants of Health and Healthcare Utilization Disparities among Older Adults with and Without Cognitive Impairment.

The purpose of this study was to determine the healthcare utilization patterns in a national sample of older adults across several social determinants of health factors (ethnicity, gender, race, education) with normal and dementia/impaired cognition. We used datasets from the Health and Retirement Study (HRS, 2018) to evaluate healthcare utilization, including metrics such as hospital and nursing home stays, hospice care, and number of visits to the doctor. Logistic models were used to predict healthcare utilization separately in those with normal cognition and dementia. Our final sample comprised 15,607 adults (mean age: 65.2 normal cognition, mean age 71.5 dementia). Hispanics with normal cognition were less likely to stay in a hospital than non-Hispanic respondents (OR: 0.52-0.71, p<0.01). Being female was associated with a higher risk for shorter nursing home days (OR: 1.41, p<0.01) and doctor visits (OR: 1.63-2, p<0.01) in cognitively normal older adults. Being female was associated with a lower risk for hospital stay in those with dementia (OR: 0.50-0.78, p<0.01). Respondents identifying as Black or other races with dementia were less likely to experience nursing home days (OR: 0.42, p<0.04). Black respondents with normal cognition were less likely to experience doctor visits (OR: 0.32-0.37, p<0.01). Those with more than a high school education in both groups were more likely to experience doctors' visits. The study points to the continued disparities in healthcare utilization linked to participants' social determinants of health factors and cognition.

Characterizing Multimorbidity Prevalence and Adverse Outcomes in Ethnically and Culturally Diverse Sub-Populations in India: Gaps, Opportunities, and Future Directions.

India is a large middle-income country and has surpassed China in overall population, comprising 20% of the global population (over 1.43 billion people). India is experiencing a major demographic shift in its aging population. Chronic diseases are common among older adults and can be persistent over the life course, lead to the onset of disability, and be costly. Among older adults in India, the existence of multiple comorbid chronic conditions (i.e., multimorbidity) is rapidly growing and represents a burgeoning public health burden. Prior research identified greater rates of multimorbidity (e.g., overweight/obesity diabetes, hypertension, cardiovascular disease, stroke, and malignancies) in minority populations in the United States (U.S.); however, limited studies have attempted to characterize multimorbidity among older adult sub-populations residing in India. To address this gap, we conducted a narrative review of studies on multimorbidity using the data from the Longitudinal Aging Study of India (LASI), the largest nationally representative longitudinal survey study of adults in India. Our definition of multimorbidity was the presence of more than two conditions in the same person. Our findings, based on 15 reviewed studies, aim to (1) characterize the definition and measurement of multimorbidity and to ascertain its prevalence in ethnically and culturally diverse sub-populations in India; (2) identify adverse outcomes associated with multimorbidity in the Indian adult population; and (3) identify gaps, opportunities, and future directions.

Polyomavirus JC urinary shedding in kidney and liver transplant recipients associated with reduced creatinine clearance.

BACKGROUND: Polyomavirus reactivation can cause significant morbidity in solid organ transplant recipients, particularly BK virus (BKV) in kidney transplant patients. Less is known about dynamics of John Cunningham virus (JCV) in nonkidney organ transplant patients. METHODS: We examined the frequency of urinary shedding of polyomaviruses BKV and JCV and their relationship to creatinine clearance (CrCl) in a longitudinal study of 41 kidney and 33 liver transplant recipients. RESULTS: Any polyomavirus urinary shedding was more frequent in liver than kidney recipients (64% vs 39%; P= .03). JCV was excreted more frequently by liver than kidney recipients (71% vs 38%), whereas BKV was shed more often by kidney than liver patients (69% vs 52%). Mean JCV loads were significantly higher than those of BKV in both patient groups (P< .0001). Lower mean CrCl values were significantly associated with JCV shedding in both kidney and liver recipients (P< .001). CONCLUSIONS: These findings suggest that BKV and JCV display different patterns of reactivation and shedding in kidney and liver transplant patients and that JCV may have a role in renal dysfunction in some solid organ transplant recipients.

Examining the Association of Pain and Pain Frequency With Self-Reported Difficulty in Activities of Daily Living and Instrumental Activities of Daily Living Among Community-Dwelling Older Adults: Findings From the Longitudinal Aging Study in India.

OBJECTIVES: We examined the prevalence and associations of self-reported difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL) with pain among community-dwelling older adults in India. We also explored the interaction effects of age and sex in these associations. METHODS: We used the Longitudinal Ageing Study in India (LASI) Wave 1 data (2017-2018). Our unweighted sample included 31,464 older adults aged 60 years and above. Outcome measures were having difficulty in at least 1 ADL/IADL. We conducted multivariable logistic regression analyses to examine the association of pain with functional difficulties controlling for selected variables. RESULTS: A total of 23.8% of older adults reported ADL and 48.4% reported IADL difficulty. Among older adults who reported pain, 33.1% reported difficulty in ADL and 57.1% reported difficulty in IADL. The adjusted odds ratio (aOR) for ADL was 1.83 (confidence interval [CI]: 1.70-1.96) and for IADL was 1.43 (CI: 1.35-1.51) when respondents reported pain compared with those without pain. Older adults who reported frequent pain had 2.28 and 1.67 times higher odds of ADL (aOR: 2.28; CI: 2.07-2.50) and IADL difficulty (aOR: 1.67; CI: 1.53-1.82) compared with those with no pain. Additionally, age and sex of the respondents significantly moderated the associations of pain and difficulty in ADL and IADL. DISCUSSION: Given the higher prevalence and likelihood of functional difficulties among older Indian adults who experienced frequent pain, interventions to mitigate pain in this vulnerable population are needed to ensure active and healthy aging.

Depression by gender and associated factors among older adults in India: implications for age-friendly policies.

Inspite of implementing policies to control mental health problems, depression remains a severe health concern among older adults in India. We examined self-reported differences in the depression among older men and women in India and examined associated factors for gender differences in depression at the population level. We utilized nationally representative data from the Longitudinal Aging Study in India (LASI) wave I, for years 2017-2019. Our analytical sample comprised of 30,637 older adults ages 60 years and above (14,682 men and 15,655 women). We conducted descriptive statistics and Chi-Square tests followed by binary logistic regression and multivariate decomposition analyses to examine our study objectives. Depression was reported in - 7.4% (95% CI 7.0, 7.8) of older men and 9.5% (CI 9.1, 10.0) of older women. Poor self-rated health, multimorbidity status, physical activity, difficulty in activities of daily living (ADL) and instrumental ADL (IADL) were the significant health-related factors associated with depression among older men and women. Not being satisfied with one's life, not being satisfied with their present living arrangement, receiving any type of ill-treatment, and being widowed were the significant factors associated with depression among older men and women. We found gender disparity in self-reported depression. Marital status contributed-to 36.7% of the gender gap in depression among older adults. Additionally, ADL and IADL difficulties among men and women contributed to 17.6% and 34.0%, gender gap, self-rated health contributed to 18.8% gap, whereas not having equal social participation (4.4%) and not satisfied in present living arrangements (8.1%) were other factors that contributed to gender gap for depression in India. Depression is a critical and persistent public health problem among-older females in India. Our findings provide a broader framework for policymakers and health practitioners to focus on gender-specific strategies to mitigate this highly emergent problem.

Assessing Intersectional Disparities in Cervical Cancer Screening by Disability Status, Race, and Ethnicity.

Introduction: Separate bodies of research have studied disparities by disability status and by race or ethnicity in receipt of cervical cancer screening. Much less is known about how these disparities intersect. The purpose of this study was to evaluate disparities in compliance with the U.S. Preventive Services Task Force guidelines for Pap testing in age-eligible women at the intersection of disability and race or ethnicity. Methods: We conducted cross-sectional analyses of the Medical Expenditure Panel Survey Household Component deidentified public data files pooled for years 2007-2016, using a modified Poisson regression analysis to compute prevalence ratios for being up to date with Pap testing by disability status and race or ethnicity. We also calculated predicted marginal proportions adjusting for demographic and socioeconomic covariates. Results: The analytic sample included 68,507 women with nonmissing covariates; 15.6% had a disability. Overall, the proportion current with Pap testing was significantly lower among women with disabilities than among those without disabilities (82.1% vs 88.6%, p<0.0001). Furthermore, within each racial and ethnic group, women with disabilities were less likely than those without disabilities to be current with Pap testing. In adjusted analyses, prevalence ratios for White women with disabilities (adjusted prevalence ratio=0.94; 95% CI=0.92, 0.96) and other race women with and without disabilities (adjusted prevalence ratio=0.91; 95% CI=0.86, 0.95 and adjusted prevalence ratio=0.91; 95% CI=0.89, 0.95, respectively) were significantly below those for the reference group of White women without disabilities. Hispanic women with disabilities did not differ significantly from White women without disabilities, and Black women with disabilities had significantly higher adjusted prevalence ratios than White women without disabilities (adjusted prevalence ratio=1.07; 95% CI=1.05, 1.09). When taking covariates into account, the proportion of Black women with disabilities current with screening was only slightly lower than the estimated proportion for Black women without disabilities (92% vs 93%). The gap in screening between White women with and without disabilities narrowed somewhat (from 9 percentage points to 4 percentage points) but remained significant. Conclusions: Our results extend previous research focused separately on disability or race and ethnicity. Women with disabilities in all racial and ethnic groups fell short of Healthy People 2020 goals for cervical cancer screening.

Rehabilitation at the Time of Pandemic: Patient Journey Recommendations.

Purpose: The World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic in March 2020, causing almost 3.5 million coronavirus disease (COVID-19) related deaths worldwide. The COVID-19 pandemic has imposed a significant burden on healthcare systems, economies, and social systems in many countries around the world. The access and delivery of rehabilitation care were severely disrupted, and patients have faced several challenges during the COVID-19 outbreak. These challenges include addressing new functional impairments faced by survivors of COVID-19 and infection prevention to avoid the virus spread to healthcare workers and other patients not infected with COVID-19. In this scoping review, we aim to develop rehabilitation recommendations during the COVID-19 pandemic across the continuum of rehabilitation care. Materials and Methods: Established frameworks were used to guide the scoping review methodology. Medline, Embase, Pubmed, CINAHL databases from inception to August 1, 2020, and prominent rehabilitation organizations' websites were searched. Study Selection: We included articles and reports if they were focused on rehabilitation recommendations for COVID-19 survivors or the general population at the time of the COVID-19 pandemic. Data Extraction: Two of our team members used the pre-tested data extraction form to extract data from included full-text articles. The strength and the quality of the extracted recommendations were evaluated by two reviewers using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Results: We retrieved 6,468 citations, of which 2,086 were eligible after removing duplicates. We excluded 1,980 citations based on the title and the abstract. Of the screened full-text articles, we included 106 studies. We present recommendations based on the patient journey at the time of the pandemic. We assessed the evidence to be of overall fair quality and strong for the recommendations. Conclusion: We have combined the latest research results and accumulated expert opinions on rehabilitation to develop acute and post-acute rehabilitation recommendations in response to the global COVID-19 pandemic. Further updates are warranted in order to incorporate the emerging evidence into rehabilitation guidelines.

Use of Connected Technologies to Assess Barriers and Stressors for Age and Disability-Friendly Communities.

Background: The benefits of engaging in outdoor physical activity are numerous for older adults. However, previous work on outdoor monitoring of physical activities did not sufficiently identify how older adults characterize and respond to diverse elements of urban built environments, including structural characteristics, safety attributes, and aesthetics. Objective: To synthesize emerging multidisciplinary trends on the use of connected technologies to assess environmental barriers and stressors among older adults and for persons with disability. Methods: A multidisciplinary overview and literature synthesis. Results: First, we review measurement and monitoring of outdoor physical activity in community environments and during transport using wearable sensing technologies, their contextualization and using smartphone-based applications. We describe physiological responses (e.g., gait patterns, electrodermal activity, brain activity, and heart rate), stressors and physical barriers during outdoor physical activity. Second, we review the use of visual data (e.g., Google street images, Street score) and machine learning algorithms to assess physical (e.g., walkability) and emotional stressors (e.g., stress) in community environments and their impact on human perception. Third, we synthesize the challenges and limitations of using real-time smartphone-based data on driving behavior, incompatibility with software data platforms, and the potential for such data to be confounded by environmental signals in older adults. Lastly, we summarize alternative modes of transport for older adults and for persons with disability. Conclusion: Environmental design for connected technologies, interventions to promote independence and mobility, and to reduce barriers and stressors, likely requires smart connected age and disability-friendly communities and cities.