Frailty Among Breast Cancer Survivors: Evidence From Swedish Population Data.

Incidence and survival of breast cancer, the most common cancer among women, have been increasing, leaving survivors at risk of aging-related health conditions. In this matched cohort study, we examined frailty risk with the Hospital Frailty Risk Score among breast cancer survivors (n = 34,900) and age-matched comparison subjects (n = 290,063). Women born in 1935-1975, registered in the Swedish Total Population Register (1991-2015), were eligible for inclusion. Survivors had a first breast cancer diagnosis in 1991-2005 and survived ≥5 years after initial diagnosis. Death date was determined by linkage to the National Cause of Death Registry (through 2015). Cancer survivorship was weakly associated with frailty (subdistribution hazard ratio (SHR) = 1.04, 95% confidence interval (CI): 1.00, 1.07). In age-stratified models, those diagnosed at younger ages (<50 years) had higher risk of frailty (SHR = 1.12, 95% CI: 1.00, 1.24) than those diagnosed at ages 50-65 (SHR = 1.03, 95% CI: 0.98, 1.07) or >65 (SHR = 1.09, 95% CI: 1.02, 1.17) years. Additionally, there was increased risk of frailty for diagnoses in 2000 or later (SHR = 1.15, 95% CI: 1.09, 1.21) compared with before 2000 (SHR = 0.97, 95% CI: 0.93, 1.17). This supports work from smaller samples showing that breast cancer survivors have increased frailty risk, particularly when diagnosed at younger ages.

Comparison of two different frailty scales in the longitudinal Swedish Adoption/Twin Study of Aging (SATSA).

AIMS: Although up to 25% of older adults are frail, assessing frailty can be difficult, especially in registry data. This study evaluated the utility of a code-based frailty score in registry data by comparing it to a gold-standard frailty score to understand how frailty can be quantified in population data and perhaps better addressed in healthcare. METHODS: We compared the Hospital Frailty Risk Score (HFRS), a frailty measure based on 109 ICD codes, to a modified version of the Frailty Index (FI) Frailty Index (FI), a self-report frailty measure, and their associations with all-cause mortality both cross-sectionally and longitudinally (follow-up = 36 years) in a Swedish cohort study (n = 1368). RESULTS: The FI and HFRS were weakly correlated (rho = 0.11, p < 0.001). Twenty-two percent (n = 297) of participants were considered frail based on published cut-offs of either measure. Only 3% (n = 35) of participants were classified as frail by both measures; 4% (n = 60) of participants were considered frail by only the HFRS; and 15% (n = 202) of participants were considered frail based only on the FI. Frailty as measured by the HFRS showed greater variance and no clear increase or decrease with age, while frailty as measured by the FI increased steadily with age. In adjusted Cox proportional hazard models, baseline HFRS frailty (HR = 1.17, 95% CI 0.92, 1.49) was not statistically significantly associated with mortality, while FI frailty was (HR = 2.89, 95% CI 1.61, 2.23). These associations were modified by age and sex. CONCLUSIONS: The HFRS may not capture the full spectrum of frailty among community-dwelling individuals, particularly at younger ages, in Swedish registry data.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up.

INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.

A review of solitary fibrous tumor/hemangiopericytoma tumor and a comparison of risk factors for recurrence, metastases, and death among patients with spinal and intracranial tumors.

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) had been combined into a single classification until 2016. Recurrence and metastases rates are still understudied, especially for spinal SFT/HPCs. Here, we describe CNS SFT/HPCs and predictors for recurrence, metastases, and death, in spinal and intracranial SFT/HPCs, separately. We collected data from studies with patient-level data available on primary SFT/HPCs from multiple online databases. Clinico-demographic data, surgical outcomes, recurrence, metastases, and death rates were abstracted. We used logistic and Cox regression models to identify predictors for recurrence, metastases, and death for spinal and intracranial SFT/HPCs. Twenty-nine studies (368 patients) were included. Higher histological grade and subtotal resection were associated with recurrence (p values < 0.05), while higher histological grade and recurrence (p values < 0.005) were associated with metastases formation. Time to recurrence (p < 0.005) and metastases (p < 0.001) formation were shorter for spinal SFT/HPCs. Death rates were higher among intracranial SFT/HPC patients (p value = 0.001). Among patients with higher histological grade, rates of metastases formation were different between intracranial and spinal SFT/HPCs. Risk of metastases was higher in the first 5 years from surgery for both intracranial and spinal SFT/HPCs. Meningeal SFT/HPCs patients have high rates of recurrence and metastasis, which occur mostly within the first 5 years after diagnosis. Spinal and intracranial SFT/HPCs show similar behavior, but spinal SFT/HPCs tend to develop metastases and recurrences in a shorter interval of time. Careful follow-up for spinal SFT/HPCs should be considered because spinal cases seem to be slightly more aggressive and require more attention.

Urology in the Time of Coronavirus: Reduced Access to Urgent and Emergent Urological Care during the Coronavirus Disease 2019 Outbreak in Italy.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has put a substantial burden on the Italian healthcare system, resulting in the restructuring of hospitals to care for COVID-19 patients. However, this has likely impacted access to care for patients experiencing other conditions. We aimed to quantify the impact of COVID-19 on access to care for patients with urgent/emergent urological conditions throughout Italy. MATERIALS AND METHODS: A questionnaire was sent to 33 urological units in the AGILE consortium, asking clinicians to report on the number of urgent/emergent urological patients seen and/or undergoing surgery over a 3-week period during the peak of the COVID-19 outbreak and a reference week prior to the outbreak. ANOVA and linear regression models were used to quantify these changes. RESULTS: Data from 27 urological centres in Italy showed a decrease from 956 patients/week seen just prior to the outbreak to 291 patients/week seen by the end of the study period. There was a difference in the number of patients with urgent/emergent urological disease seen within/during the different weeks (all p values < 0.05). A significant decrease in the number of patients presenting with haematuria, urinary retention, urinary tract infection, scrotal pain, renal colic, or trauma and urgent/emergent cases that required surgery was reported (all p values < 0.05). CONCLUSION: In Italy, during the COVID-19 outbreak there has been a decrease in patients seeking help for urgent/emergent urological conditions. Restructuring of hospitals and clinics is mandatory to cope with the COVID-19 pandemic; however, the healthcare system should continue to provide adequate levels of care also to patients with other conditions.

Napping characteristics and cognitive performance in older adults.

OBJECTIVES: To determine the association of napping intention, frequency, and duration with cognition in a nationally-representative sample of US older adults. METHODS: We performed a cross-sectional analysis of community-dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013-2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past-month napping intention (intentional/unintentional), napping frequency (rarely/never [non-nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31-60 minutes [moderate]; and > 60 minutes [long]). Cognitive outcomes were performance on immediate and delayed word recall tests (IWR and DWR, respectively), the Clock Drawing Test (CDT), and self-rated memory (score: 1[excellent]-5[very poor]). RESULTS: After adjustment for potential confounders, unintentional nappers had poorer immediate word recall test performance than non-nappers (B = -0.23, P < 0.01) and intentional nappers (B = -0.26, P < 0.01). After further adjustment for daytime sleepiness, frequent nappers reported poorer self-rated memory than non-nappers (B = 0.14, P < 0.05). Compared with short nappers, long nappers had poorer IWR (B = -0.26, P < 0.05) and CDT scores (B = -0.17, P < 0.05). Except for the association of nap duration with IWR and CDT, these associations remained after excluding participants with dementia and/or proxy respondents. Among participants undiagnosed with dementia or proxies, moderate-duration naps were associated with better DWR than short naps (B = 0.24, P < 0.05). Neither napping intentionality nor frequency was associated with CDT performance. CONCLUSIONS: Among older adults, distinct aspects of napping are associated with cognitive performance. Prospective research, with objective measures of napping, is needed to elucidate the link between napping and cognitive trajectories.

Stressful life events and cognitive decline: Sex differences in the Baltimore Epidemiologic Catchment Area Follow-Up Study.

INTRODUCTION: The reasons why women are at higher risk than men for developing dementia are unclear. Although studies implicate sex differences in the effect of stress on cognitive functioning, whether stressful life events are associated with subsequent cognitive decline has received scant research attention. METHODS: In Wave 3 (1993-1996) of the Baltimore Epidemiologic Catchment Area study, 337 men and 572 women (mean age = 47 years) reported recent (within the last year) and remote (from 1981 until 1 year ago) traumatic events (eg, combat) and stressful life events (eg, divorce/separation). At Waves 3 and 4 (2004-2005), they completed the Mini Mental State Examination (MMSE) and a word-list memory test. Multivariable models were used to examine the association between traumatic and stressful life events at Wave 3 and cognitive change by Wave 4. RESULTS: A greater number of recent stressful life events at Wave 3, but not of more remote stressful events, was associated with greater verbal memory decline by Wave 4 in women but not in men. Stressful events were not associated with change in MMSE, and there were no associations between traumatic events occurring at any time and subsequent memory or MMSE decline in either sex. CONCLUSIONS: Unlike men, middle-aged women with a greater number of recent stressful life events demonstrate memory decline over a decade later. Sex differences in cognitive vulnerability to stressful life events may underlie women's increased risk of memory impairment in late life, suggesting that stress reduction interventions may help prevent cognitive decline in women.

Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging.

OBJECTIVE: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. METHODS: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. RESULTS: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P < .001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P = .009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P = .014) use were also associated with risk of MCI diagnosis. CONCLUSIONS: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

Association between Various Brain Pathologies and Gait Disturbance.

BACKGROUND: Approximately 30% of older adults have disrupted gait. It is associated with increased risk of cognitive decline, disability, dementia, and death. Additionally, most older adults present with 1 or more neuropathologies at autopsy. Recently, there has been an effort to investigate the association between subclinical neuropathology and gait. SUMMARY: We reviewed studies that investigated the association between gait and neuropathologies. Although all pathologies reviewed were associated with gait, grey matter atrophy was most consistently linked with poorer gait performance. Studies investigating the association between white matter and gait focused primarily on total white matter. Future research using more parsed regional analysis will provide more insight into this relationship. Evidence from studies investigating neuronal activity and gait suggests that gait disruption is associated with both under- and overactivation. Additional research is needed to delineate these conflicting results. Lastly, early evidence suggests that both amyloid and tau aggregation negatively impact multiple gait parameters, but additional studies are warranted. Overall, there was substantial methodological heterogeneity and a paucity of longitudinal studies. Key Messages: Longitudinal studies mapping changes in different types of neuropathology as they relate to changes in multiple gait parameters are needed to better understand trajectories of pathology and gait.

Family history and TOMM40 '523 interactive associations with memory in middle-aged and Alzheimer's disease cohorts.

INTRODUCTION: Family history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa (TOMM40) rs10524523 ('523) poly-T length on memory decline. METHODS: For 912 nonapolipoprotein ε4 middle-aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 '523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal fluid mitochondrial function biomarker was also assessed. RESULTS: For FH negative participants, gene-dose preservation of memory and global cognition was seen for "very long" versus "short" carriers. For FH positive, an opposite gene-dose decline was seen for very long versus short carriers. Maternal FH was a stronger predictor in aged, but not middle-aged, participants. Similar gene-dose effects were seen for the mitochondrial biomarker aspartate aminotransferase. DISCUSSION: These results may clarify conflicting findings on TOMM40 poly-T length and AD-related decline.

Racial/Ethnic Differences in Insomnia Trajectories Among U.S. Older Adults.

OBJECTIVES: Insomnia is reported to be more prevalent in minority racial/ethnic groups. Little is known, however, about racial/ethnic differences in changes in insomnia severity over time, particularly among older adults. We examined racial/ethnic differences in trajectories of insomnia severity among middle-aged and older adults. DESIGN: Data were drawn from five waves of the Health and Retirement Study (2002-2010), a nationally representative longitudinal biennial survey of adults aged > 50 years. SETTING: Population-based. PARTICIPANTS: 22,252 participants from non-Hispanic white, non-Hispanic black, Hispanic, and other racial/ethnic groups. MEASUREMENTS: Participants reported the severity of four insomnia symptoms; summed scores ranged from 4 (no insomnia) to 12 (severe insomnia). We assessed change in insomnia across the five waves as a function of race/ethnicity. RESULTS: Across all participants, insomnia severity scores increased 0.19 points (95% CI: 0.14-0.24; t = 7.52; design df = 56; p < 0.001) over time after adjustment for sex, race/ethnicity, education, and baseline age. After adjusting for the number of accumulated health conditions and body mass index, this trend decreased substantially and even changed direction (B = -0.24; 95% CI: -0.29 to -0.19; t = -9.22; design df = 56; p < 0.001). The increasing trajectory was significantly more pronounced in Hispanics compared with non-Hispanic whites, even after adjustment for number of accumulated health conditions, body mass index, and number of depressive symptoms. CONCLUSIONS: Although insomnia severity increases with age-largely due to the accumulation of health conditions-this trend appears more pronounced among Hispanic older adults than in non-Hispanic whites. Further research is needed to determine the reasons for a different insomnia trajectory among Hispanics.

Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort.

INTRODUCTION: Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimer's disease (AD)-related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals. METHODS: Participants included 378 cognitively normal (CN) and 161 mild cognitive impairment (MCI) individuals enrolled in the Mayo Clinic Study of Aging with concurrent neuropsychological measures and amyloid PET, fluorodeoxyglucose PET, and MRI. Baseline plasma tau levels were measured using the Quanterix Simoa-HD1 tau assay. RESULTS: Plasma tau levels were higher in MCI compared with CN (4.34 vs. 4.14 pg/mL, P = .078). In regression models adjusted for age, gender, education, and APOE, higher plasma tau was associated with worse memory performance (b = -0.30, P = .02) and abnormal cortical thickness in an AD signature region (odds ratio = 1.80, P = .018). DISCUSSION: Plasma tau is associated with cortical thickness and memory performance. Longitudinal studies will better elucidate the associations between plasma tau, neurodegeneration, and cognition.

Neighborhood physical disorder, social cohesion, and insomnia: results from participants over age 50 in the Health and Retirement Study.

ABSTRACT Background: We determined the association between neighborhood socio-environmental factors and insomnia symptoms in a nationally representative sample of US adults aged >50 years. Methods: Data were analyzed from two waves (2006 and 2010) of the Health and Retirement Study using 7,231 community-dwelling participants (3,054 men and 4,177 women) in the United States. Primary predictors were neighborhood physical disorder (e.g. vandalism/graffiti, feeling safe alone after dark, and cleanliness) and social cohesion (e.g. friendliness of people, availability of help when needed, etc.); outcomes were insomnia symptoms (trouble falling asleep, night awakenings, waking too early, and feeling unrested). Results: After adjustment for age, income, race, education, sex, chronic diseases, body mass index, depressive symptoms, smoking, and alcohol consumption, each one-unit increase in neighborhood physical disorder was associated with a greater odds of trouble falling asleep (odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.04-1.14), waking too early (OR = 1.05, 95% CI: 1.00-1.10), and, in adults aged ≥69 years (adjusting for all variables above except age), feeling unrested in the morning (OR = 1.11, 95% CI: 1.02-1.22 in 2006). Each one-unit increase in lower social cohesion was associated with a greater odds of trouble falling asleep (OR = 1.06, 95% CI: 1.01-1.11) and feeling unrested (OR = 1.09, 95% CI: 1.04-1.15). Conclusions: Neighborhood-level factors of physical disorder and social cohesion are associated with insomnia symptoms in middle-aged and older adults. Neighborhood-level factors may affect sleep, and consequently health, in our aging population.

Diabetes and cognitive outcomes in a nationally representative sample: the National Health and Aging Trends Study.

BACKGROUND: The prevalence of both type II diabetes mellitus (DM) and cognitive impairment is high and increasing in older adults. We examined the extent to which DM diagnosis was associated with poorer cognitive performance and dementia diagnosis in a population-based cohort of US older adults. METHODS: We studied 7,606 participants in the National Health and Aging Trends Study, a nationally representative cohort of Medicare beneficiaries aged 65 years and older. DM and dementia diagnosis were based on self-report from participants or proxy respondents, and participants completed a word-list memory test, the Clock Drawing Test, and gave a subjective assessment of their own memory. RESULTS: In unadjusted analyses, self-reported DM diagnosis was associated with poorer immediate and delayed word recall, worse performance on the Clock Drawing Test, and poorer self-rated memory. After adjusting for demographic characteristics, body mass index, depression and anxiety symptoms, and medical conditions, DM was associated with poorer immediate and delayed word recall and poorer self-rated memory, but not with the Clock Drawing Test performance or self-reported dementia diagnosis. After excluding participants with a history of stroke, DM diagnosis was associated with poorer immediate and delayed word recall and the Clock Drawing Test performance, and poorer self-rated memory, but not with self-reported dementia diagnosis. CONCLUSIONS: In this recent representative sample of older Medicare enrollees, self-reported DM was associated with poorer cognitive test performance. Findings provide further support for DM as a potential risk factor for poor cognitive outcomes. Studies are needed that investigate whether DM treatment prevents cognitive decline.

Characterizing the Individuals Who Regain or Maintain Walking Ability after a Hip Fracture: Insights Into Physical Resilience.

OBJECTIVES: Maintaining walking ability is key to healthy aging. Hip fractures often lead to declined walking ability. This study investigated characteristics of individuals who regained walking ability after a hip fracture, an expression of physical resilience. DESIGN: Register-based cohort study. SETTING AND PARTICIPANTS: A total of 55,467 Swedish residents aged ≥60 years with a first hip fracture (71% women, mean age = 82.3 ± 8) included in the Swedish Hip Fracture Register. METHODS: Information about diseases, medications, and socioeconomic (SES) factors came from registers. Individuals were classified by prefracture walking ability (independent or assisted walking) and whether their walking ability 4 months post-fracture was maintained (physical resilience or nonresilience). Cluster analyses were conducted among individuals who maintained their walking ability to assess different physical resilience profiles. RESULTS: At baseline, 38,493 individuals walked independently (69%), and 16,982 were assisted walkers. Half of the independent walkers maintained their walking ability 4 months post-fracture. Among them, 3 clusters were identified: a "Low SES, Low Disease" cluster (n = 8580, mean age 81.1 ± 7.5); a "High SES, Low Disease" cluster (n = 7778, mean age 76.7 ± 7.4); and a third "High SES, High Disease" cluster (n = 4320, mean age 77.7 ± 7.4). Sixty percent of the pre-assisted walkers maintained their level of assisted walking ability. Also among them, 3 clusters were identified: a "Low SES-Independent Living" cluster (n = 3077, mean age 85.5 ± 7.1); a second "Care Home" cluster (n = 2912, mean age 87.0 ± 6.5) with a high proportion with dementia diagnosis; and a last "High SES" cluster (n = 4044, mean age 83.0 ± 7.0) with the largest proportion of men. CONCLUSIONS AND IMPLICATIONS: Physical resilience is not characterized by one typical healthy profile, and it is possible to regain walking ability after a hip fracture despite unfavorable prerequisites in 1 domain. A favorable status in one domain may compensate for an unfavorable status in another, for example, a high disease burden in combination with high SES.

Trends in Frailty Between 1990 and 2020 in Sweden Among 75-, 85-, and 95-Year-Old Women and Men: A Nationwide Study from Sweden.

BACKGROUND: Aging is the primary risk factor for frailty, which is defined as an inability to respond to acute or chronic stressors. Individuals are living longer with greater multimorbidity, but there is a paucity of evidence examining frailty across birth cohorts and ages. METHODS: We investigated frailty prevalence and its association with mortality at ages 75, 85, and 95 in the 1895-1945 birth cohorts in Sweden with data from population registries. Frailty was assessed with the Hospital Frailty Risk Score (HFRS). RESULTS: We observed that frailty increased with increasing age and that it has become more common in more recent birth cohorts. At age 75, the percent frail in the Total Population Register increased from 1.1% to 4.6% from birth cohorts 1915-1945, corresponding to calendar years 1990-2020. At age 85, the percentage of frail increased from 3.5% to 11.5% from birth cohorts 1905-1935, and at age 95 from birth cohorts 1895-1925, from 4.7% to 18.7%. Our results show that the increase was primarily driven by an increase in the distribution of individuals with scores in the highest quartile of HFRS, while the bottom 3 quartiles remained relatively stable across birth cohorts. Women accounted for a greater distribution of the overall population and frail population, though these disparities decreased over time. Despite increasing levels of frailty, the relationship between frailty and mortality did not change over time, nor did it differ by sex. CONCLUSION: Increased frailty with improved survival points to a chronic condition that could be intervened upon.

How both positive and burdensome caregiver experiences are associated with care recipient cognitive performance: Evidence from the National Health and Aging Trends Study and National Study of Caregiving.

Introduction: Being an informal caregiver to a person with chronic disease, including persons living with dementia (PLWD), is a big role to take on and many caregivers experience both substantial burden and emotional reward related to caregiving. Care recipient factors (e.g., behavioral symptoms) are associated with caregiver experience. However, the relationship between caregiver and care recipient is bidirectional, so it is likely that caregiver factors impact the care recipient, though few studies have investigated this. Methods: In the 2017 round of the National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC), we studied 1,210 care dyads--170 PLWD dyads and 1,040 without dementia dyads. Care recipients completed immediate and delayed word list memory tasks, the Clock Drawing Test, and a self-rated memory rating, while caregivers were interviewed about their caregiving experiences using a 34-item questionnaire. Using principal component analysis, we created a caregiver experience score with three components-Practical Care Burden, Positive Care Experiences, and Emotional Care Burden. We then investigated the cross-sectional association between caregiver experience components and care recipient cognitive test performance using linear regression models adjusted for age, sex, education, race, and depressive and anxiety symptoms. Results: Among PLWD dyads, a higher caregiver Positive Care Experiences score was associated with better care recipient performance on the delayed word recall (B = 0.20, 95% CI 0.05, 0.36) and Clock Draw (B = 0.12, 95% CI 0.01, 0.24) tests while higher Emotional Care Burden score was associated with worse self-rated memory score (B = -0.19, 95% CI -0.39, -0.003). Among participants without dementia, higher Practical Care Burden score was associated with poorer care recipient performance on the immediate (B = -0.07, 95% CI -0.12, -0.01) and delayed (B = -0.10, 95% CI -0.16, -0.05) word recall tests. Discussion: These findings support the concept that caregiving is bidirectional within the dyad and that positive variables can positively impact both members of the dyad. This suggests that caregiving interventions should target the caregiver and recipient both individually and as a unit, with the goal of holistically improving outcomes for both.

The pollutome-connectome axis: a putative mechanism to explain pollution effects on neurodegeneration.

The study of pollutant effects is extremely important to address the epochal challenges we are facing, where world populations are increasingly moving from rural to urban centers, revolutionizing our world into an urban world. These transformations will exacerbate pollution, thus highlighting the necessity to unravel its effect on human health. Epidemiological studies have reported that pollution increases the risk of neurological diseases, with growing evidence on the risk of neurodegenerative disorders. Air pollution and water pollutants are the main chemicals driving this risk. These chemicals can promote inflammation, acting in synergy with genotype vulnerability. However, the biological underpinnings of this association are unknown. In this review, we focus on the link between pollution and brain network connectivity at the macro-scale level. We provide an updated overview of epidemiological findings and studies investigating brain network changes associated with pollution exposure, and discuss the mechanistic insights of pollution-induced brain changes through neural networks. We explain, in detail, the pollutome-connectome axis that might provide the functional substrate for pollution-induced processes leading to cognitive impairment and neurodegeneration. We describe this model within the framework of two pollutants, air pollution, a widely recognized threat, and polyfluoroalkyl substances, a large class of synthetic chemicals which are currently emerging as new neurotoxic source.