Plasma proteins related to inflammatory diet predict future cognitive impairment.

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aß42/40) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

Pattern Recognition to Objectively Differentiate the Etiology of Cognitive Decline: Analysis of the Impact of Stroke and Alzheimer's Disease.

BACKGROUND: Undetected Alzheimer's disease (AD) and stroke neuropathology is believed to account for a large proportion of decline in cognitive performance that is attributed to normal aging. This study examined the amount of variance in age-related cognitive change that is accounted for by AD and stroke using a novel pattern recognition protocol. METHOD: Secondary analyses of data collected for the Health and Retirement Study (N = 17,579) were used to objectively characterize patterns of cognitive decline associated with AD and stroke. The rate of decline in episodic memory and orientation was the outcome of interest, while algorithms indicative of AD and stroke pathology were the predictors of interest. RESULTS: The average age of the sample was 67.54 ± 10.45 years at baseline, and they completed, on average, 14.20 ± 3.56 years of follow-up. After adjusting for demographics, AD and stroke accounted for approximately half of age-associated decline in cognition (51.07-55.6% for orientation and episodic memory, respectively) and explained variance attributed to random slopes in longitudinal multilevel models. DISCUSSION: The results of this study suggested that approximately half of the cognitive decline usually attributed to normal aging are more characteristic of AD and stroke.

Marital Status and Return to Work After Living Kidney Donation.

PURPOSE: Living kidney donation is safe and effective, but patients in need of a transplant continue to outnumber donors. Disincentives to living donation include lost income, risk of job loss, perioperative complications, and unreimbursed medical expenses. METHODS: This study uses US registry and follow-up data on living kidney donors from 2013 to 2015 to identify social predictors of return to work across gender following living kidney donation. RESULTS: Using logistic regression, we find that predictors of return to work following living kidney donation differ for women and men. Among women, age, education, smoking status, and procedure type are associated with return to work. Among men, education, procedure type, and hospital readmission within 6 weeks postdonation are associated with return to work. Notably, single and divorced men are less likely to return to work compared to married men (odds ratio [OR] for single men 0.51, 95% confidence interval [CI], 0.37-0.69, P < .001; OR for divorced men 0.51, 95% CI, 0.34-0.75, P = .006). Marital status is not associated with return to work for women. Single and divorced men's greater odds of not returning to work are robust to controls for relevant pre- and postdonation characteristics. CONCLUSIONS: Single and divorced men's lack of social support may present an obstacle to work resumption following living kidney donation.

Couples' employment after spousal kidney donation.

We used data from the United Network for Organ Sharing registry of living kidney donors and recipients to identify correlates of paid employment among couples following spousal living donation. Among such couples, post-transplant employment of both spouses (41%) was as common as employment of the donor only (41%). However, when the recipient was female, donor-only employment after transplant was more than twice as likely as compared to employment of both spouses (relative risk ratio = 2.57; p < .001). We conclude that traditional gender roles regarding paid workforce participation may be associated with the likelihood of employment after spousal kidney donation.

Obesity in Late-Life as a Protective Factor Against Dementia and Dementia-Related Mortality.

OBJECTIVE: We estimated the conversion from cognitively normal to mild cognitive impairment (MCI) to probable dementia and death for underweight, normal, overweight, and obese older adults, where the timing of examinations is associated with the severity of dementia. METHODS: We analyzed six waves of the National Health and Aging Trends Study (NHATS). Body mass (BMI) was computed from height and weight. Multi-state survival models (MSMs) examined misclassification probability, time-to-event ratios, and cognitive decline. RESULTS: Participants (n = 6078) were 77 years old, 62% had overweight and/or obese BMI. After adjusting for the effects of cardiometabolic factors, age, sex, and race, obesity was protective against developing dementia (aHR=.44; 95%CI [.29-.67]) and dementia-related mortality (aHR=.63; 95%CI [.42-.95]). DISCUSSION: We found a negative relationship between obesity and dementia and dementia-related mortality, a finding that has been underreported in the literature. The continuing obesity epidemic might complicate the diagnosis and treatment of dementia.

Glial suppression and post-traumatic stress disorder: A cross-sectional study of 1,520 world trade center responders.

Background: Chronically re-experiencing the memory of a traumatic event might cause a glial response. This study examined whether glial activation would be associated with PTSD in a study of responders present after the 9/11 World Trade Center attacks without comorbid cerebrovascular disease. Methods: Plasma was retrieved from 1,520 WTC responders and stored for a cross-sectional sample of responders of varying levels of exposure and PTSD. Plasma levels (pg/ml) of glial fibrillary acidic protein (GFAP) were assayed. Because stroke and other cerebrovascular diseases cause distributional shifts in GFAP levels, multivariable-adjusted finite mixture models analyzed GFAP distributions in responders with and without possible cerebrovascular disease. Results: Responders were aged 56.3 years and primarily male; 11.07% (n = 154) had chronic PTSD. Older age was associated with increased GFAP, whereas higher body mass was associated with decreased GFAP. Multivariable-adjusted finite mixture models revealed that severe re-experiencing trauma from 9/11 was associated with lower GFAP (B = -0.558, p = 0.003). Conclusion: This study presents evidence of reduced plasma GFAP levels among WTC responders with PTSD. Results suggest re-experiencing traumatic events might cause glial suppression.

Association of Later-Life Weight Changes With Survival to Ages 90, 95, and 100: The Women's Health Initiative.

BACKGROUND: Associations of weight changes and intentionality of weight loss with longevity are not well described. METHODS: Using longitudinal data from the Women's Health Initiative (N = 54 437; 61-81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured at baseline, year 3, and year 10, and participants were classified as having weight loss (≥5% decrease from baseline), weight gain (≥5% increase from baseline), or stable weight (<5% change from baseline). Participants reported intentionality of weight loss at year 3. RESULTS: A total of 30 647 (56.3%) women survived to ≥90 years. After adjustment for relevant covariates, 3-year weight loss of ≥5% vs stable weight was associated with lower odds of survival to ages 90 (OR, 0.67; 95% CI, 0.64-0.71), 95 (OR, 0.65; 95% CI, 0.60-0.71), and 100 (OR, 0.62; 95% CI, 0.49-0.78). Compared to intentional weight loss, unintentional weight loss was more strongly associated with lower odds of survival to age 90 (OR, 0.83; 95% CI, 0.74-0.94 and OR, 0.49; 95% CI, 0.44-0.55, respectively). Three-year weight gain of ≥5% vs stable weight was not associated with survival to age 90, 95, or 100. The pattern of results was similar among normal weight, overweight, and obese women in body mass index (BMI)-stratified analyses. CONCLUSIONS: Weight loss of ≥5% vs stable weight was associated with lower odds of longevity, more strongly for unintentional weight loss than for intentional weight loss. Potential inaccuracy of self-reported intentionality of weight loss and residual confounding were limitations.

Elevated C-Reactive Protein in Alzheimer's Disease Without Depression in Older Adults: Findings From the Health and Retirement Study.

We examined the association between differential diagnoses of major stroke and probable Alzheimer's disease (AD) and mixed AD on C-reactive protein (CRP) in older adults with and without depression. Secondary data analyses examined associations between blood-based measures of probable peripheral inflammation using CRP collected from dried blood spots in the Health and Retirement Study, a nationally representative sample of individuals aged 50 and older. A validated pattern-recognition algorithm was utilized to identify cognitive decline indicative of probable AD, mixed AD, and major stroke. Negative binomial regressions were utilized to model concentrations of serologic CRP. On average, participants (N = 4 601) were 70 years old, female, and non-Hispanic White. Mixed AD participants had a 0.26 mg/dL increase in CRP compared to unimpaired participants, controlling for demographics, health behaviors, and comorbidities. Those with mixed AD had 2.14 times increased odds of having high CRP (odds ratio = 2.14 [1.19-3.85]). In analyses stratified by depression, adults with mixed AD and without depression had an additional 0.37 mg/dL increase in CRP (SE = 0.06; p < .001) compared to unimpaired adults. Those with AD without depression had a 0.20 mg/dL increase in CRP (SE = 0.07; p < .01). Age was not associated with increased CRP in nondepressed older adults. Depressed adults with major stroke had a -0.26 mg/dL decrease in CRP (SE = 0.11; p = .02), controlling for hypertension, alcoholic drinks/beverages per week, and smoking status. Concentration modeling revealed that participants with major stroke, probable AD, and probable mixed AD without depression had significantly higher CRP concentrations when compared to unimpaired older adults.

Ventricular Assist Device Technology and Black-White Disparities on the Heart Transplant Wait List.

INTRODUCTION: Heart transplantation is the definitive treatment for end-stage heart failure. Left ventricular assist devices (LVADs) are a continually improving technology that extends life for some candidates on the heart transplant waiting list. Research Questions: Our objective is to compare Black-White differences in LVAD implantation and heart transplant outcomes during a period of technological innovation when the pulsatile flow LVAD was largely replaced by the continuous flow LVAD between 1999-2014. DESIGN: We used transplant registry data from the United Network for Organ Sharing (N = 5,550) to identify Black and White patients with heart failure who used an LVAD as a bridge-to-transplant (BTT). Using logistic regression, we compared Black-White differences in access to newer LVAD technology and timing of implantation relative to wait listing for heart transplantation. We used competing-risks event history models to predict transplant outcomes across race, LVAD type, and timing of LVAD implantation. RESULTS: Black and White candidates were equally likely to receive newer continuous flow LVADs, but Black candidates received LVADs later in the disease course (i.e. after transplant listing). This later timing of technological intervention contributed to poorer wait list outcomes among black transplant candidates, including lower likelihood of receiving a heart transplant and greater likelihood of being removed from the wait list due to worsening health. DISCUSSION: Delayed LVAD implantation is more common among Black patients and is associated with poorer transplant outcomes.

The Characteristics of Social Network Structure in Later Life in Relation to Incidence of Mild Cognitive Impairment and Conversion to Probable Dementia.

BACKGROUND: Larger, more active social networks are estimated to be associated with lower risks of cognitive decline. However, roles of various social relationships in a broad social network in protecting against cognitive decline remain to be elucidated. OBJECTIVE: We aimed to investigate how social roles within a social network and number of social network members are associated with cognitive decline. METHODS: Six waves of National Health and Aging Trends Study (2011-2016, NHATS) were utilized to examine the development of mild cognitive impairment (MCI) and probable dementia determined using validated criteria. Multivariable-adjusted multi-state survival models were used to model incidences and transitions, jointly with misclassification errors. RESULTS: A total of 6,078 eligible NHATS participants were included (average age: 77.49±7.79 years; female: 58.42%; non-Hispanic white: 68.99%). Multivariable-adjusted analyses revealed that having more social network members was associated with lower hazards of conversion from MCI to probable dementia (adjusted Hazard Ratio; aHR = 0.82; 95%confidence intervals; 95%CI = [0.67-0.99]), meanwhile having at least one college-educated family member within a social network was associated with lower incidence of probable dementia (aHR = 0.37 [0.26-0.51]). Having at least one friend within a social network was associated with a lower hazard of incidence of probable dementia (aHR = 0.48 [0.33-0.71]), but a higher risk of mortality in the MCI group (aHR = 2.58 [1.47-4.51]). CONCLUSION: Having more social network members, having at least one friend, and having at least one college-educated family member within a social network, were associated with lower risks of incidence of dementia or conversion from MCI to dementia.

Incidence of Mild Cognitive Impairment, Conversion to Probable Dementia, and Mortality.

BACKGROUND: Few studies have jointly estimated incidence of MCI, conversion to probable dementia, and mortality in a nationally representatie sample. METHODS: We used data from six waves of the National Health and Aging Trends Study (2011-2016). Multivariable-adjusted multi-state survival models (MSMs) were used to model incidence upon accounting for misclassification. RESULTS: A total of 6,078 eligible NHATS participants were included (average age: 77.49 ± 7.79 years; 58.42% females; 68.99% non-Hispanic white). The incidence of MCI was estimated to be 41.0 [35.5, 47.3]/1,000 person-years (PY). Participants converted to probable dementia at a high rate of 241.3 [189.6, 307.0]/1,000 PY, though a small number also reverted from MCI to cognitively normal. Education was associated with lower incidence of MCI and conversion to probable dementia, but increased mortality in those with MCI. There were also substantial racial and ethnic disparities in the incidence of MCI and dementia. CONCLUSIONS: Our results underscore the relatively common incidence of and conversions between MCI and dementia in community-dwelling older Americans and uncover the beneficial impact of education to withstand cognitive impairment before death.

Socioeconomic inequalities in the spread of coronavirus-19 in the United States: A examination of the emergence of social inequalities.

OBJECTIVES: To quantify the contribution variation in socioeconomic status in predicting the distribution of COVID-19 cases and deaths. METHODS: Analyses used incidence data on daily COVID + case counts from all counties from the initial wave of infections, merged with data from the U.S. census data to measure county-level SES and confounders. Multivariable analyses relied on survival analyses and Poisson regression to examine timing of county-level index cases and of COVID-19 incidence and mortality in infected counties to examine the spread and severity of COVID-19 while adjusting for adjusted for Black race, Hispanic ethnicity, age, gender, and urbanicity. Effect moderation by social distancing parameters was examined. RESULTS: Results indicate that higher SES was associated with earlier incidence of index cases, but that as social distancing took place inequalities in SES inverted so that growth in incidence was slower in higher SES counties, where case-fatality rates were lower. CONCLUSIONS: This study is the first to date to show what happens when an opportunistic disease that could affect anyone meets the American system of inequality and is powerfully shaped by it.