Unhealthy white matter connectivity, cognition, and racialization in older adults.

INTRODUCTION: White matter hyperintensities (WMH) may promote clinical Alzheimer's disease (AD) disparities between Black American (BA) and non-Hispanic White (nHW) populations. Using a novel measurement, unhealthy white matter connectivity (UWMC), we interrogated racialized group differences in associations between WMH in AD pathology-affected regions and cognition. METHODS: UWMC is the proportion of white matter fibers that pass through WMH for every pair of brain regions. Individual regression models tested associations of UWMC in beta-amyloid (Aß) or tau pathology-affected regions with cognition overall, stratified by racialized group, and with a racialized group interaction. RESULTS: In 201 older adults ranging from cognitively unimpaired to AD, BA participants exhibited greater UWMC and worse cognition than nHW participants. UWMC was negatively associated with cognition in 17 and 5 Aß- and tau-affected regions, respectively. Racialization did not modify these relationships. DISCUSSION: Differential UWMC burden, not differential UWMC-and-cognition associations, may drive clinical AD disparities between racialized groups. HIGHLIGHTS: Unhealthy white matter connectivity (UWMC) in Alzheimer's disease (AD) pathology-affected brain regions is associated with cognition. Relationships between UWMC and cognition are similar between Black American (BA) and non-Hispanic White (nHW) individuals. More UWMC may partially drive higher clinical AD burden in BA versus nHW populations. UWMC risk factors, particularly social and environmental, should be identified.

Functional correlates of self-reported energy levels in the Health, Aging and Body Composition Study.

BACKGROUND: Effects of fatigue on health in older age are well studied, yet little is known about the clinical relevance of energy perception. AIMS: To explore cross-sectional associations of self-reported energy with physical and mental health metrics in the Health, Aging, and Body Composition Study. METHODS: Participants rated their energy from 0 to 10; the outcome was energy dichotomized at the median (≥ 7 = higher energy). Four domains were assessed: depressive symptoms (Center for Epidemiologic Studies Depression Scale); physical performance (function: usual and rapid gait speed; fitness: 400-m walk time); physical activity (casual walking, walking for exercise, and intense exercise); and cognitive function (Modified Mini-Mental State Examination and Digit Symbol Substitution Test). Covariates bivariately associated with energy entered a multivariable logistic regression model, adjusted for demographics, chronic conditions, and strength. RESULTS: Depressive symptoms, physical performance and activity, but not cognition, were bivariately associated with energy (p < 0.0005). Younger age, male sex, greater strength, and absence of chronic conditions predicted higher energy (p < 0.001). In a multivariable model, depressive symptoms [adjusted odds ratio (aOR) 95% CI 0.69 (0.62, 0.76)] and 400-m walk times [aOR = 0.81 (0.72, 0.91)] were inversely associated with energy; usual and rapid gait speed [aOR = 1.3 (1.2, 1.4); aOR = 1.2 (1.1-1.4)], and time spent in intense exercise [aOR = 1.4 (1.1-1.7)] were positively associated with energy. DISCUSSION: In this cohort with a range of chronic conditions and fatigue, perceiving higher energy levels may reflect better emotional and physical health. CONCLUSION: Energy should be considered in multidimensional clinical assessments of older age.

Analysis of eligibility criteria in Alzheimer's and related dementias clinical trials.

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.

Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates.

PURPOSE: Declining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time. METHODS: We examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities. RESULTS: Higher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant. CONCLUSIONS: In this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted.

Longitudinal Associations Between Higher Self-Reported Energy, Gait Speed, and Cognition in Older Adults With Fatigue.

BACKGROUND: Older adults reporting higher energy levels have better physical function. It is not known if these associations persist among older adults reporting fatigue or if higher energy is associated with cognitive function. We examined longitudinal associations between self-reported energy, gait speed, and cognition, stratified by fatigue, in 2 613 participants (aged 74.6 ±â€…2.87 years) in the Health, Aging and Body Composition Study. METHODS: Self-reported energy (0-10, dichotomized at median) and fatigue (present/absent) were measured at baseline. Usual and rapid-paced gait speed (m/s), modified Mini-Mental State Examination (3MS), and Digit Symbol Substitution Test (DSST) were measured at baseline and annually over 8 years. Linear mixed effect models compared changes in gait speed, 3MS, and DSST between higher and lower energy groups within fatigue strata. RESULTS: At baseline, 724 participants (27%) were fatigued; 240 (33%) coreported higher energy (9% of total). The remaining 1 889 participants were fatigue-free (73%); 1 221 (65%) coreported higher energy (47% of total). Those with fatigue and higher energy had average rapid gait declines of 0.007 m/s per year (p = .04) after adjustment for demographics, comorbidities, depressive symptoms, and exercise. DSST declines were found among only fatigue-free participants (ß = 0.17, p = .01). No statistically significant associations with energy were found for fatigue-free participants, or for usual gait or 3MS. CONCLUSIONS: Asking about older adults' energy levels as well as fatigue may identify a subgroup of older adults protected against physical and cognitive decline, even among those with fatigue.

Mild Parkinsonian Signs, Energy Decline, and Striatal Volume in Community-Dwelling Older Adults.

BACKGROUND: Mild parkinsonian signs (MPS), highly prevalent in older adults, predict disability. It is unknown whether energy decline, a predictor of mobility disability, is also associated with MPS. We hypothesized that those with MPS had greater decline in self-reported energy level (SEL) than those without MPS, and that SEL decline and MPS share neural substrates. METHOD: Using data from the Health, Aging and Body Composition Study, we analyzed 293 Parkinson's disease-free participants (83 ± 3 years old, 39% Black, 58% women) with neuroimaging data, MPS evaluation by Unified Parkinson Disease Rating Scale in 2006-2008, and ≥3 measures of SEL since 1999-2000. Individual SEL slopes were computed via linear mixed models. Associations of SEL slopes with MPS were tested using logistic regression models. Associations of SEL slope with volume of striatum, sensorimotor, and cognitive regions were examined using linear regression models adjusted for normalized total gray matter volume. Models were adjusted for baseline SEL, mobility, demographics, and comorbidities. RESULTS: Compared to those without MPS (n = 165), those with MPS (n = 128) had 37% greater SEL decline in the prior 8 years (p = .001). Greater SEL decline was associated with smaller right striatal volume (adjusted standardized ß = 0.126, p = .029). SEL decline was not associated with volumes in other regions. The association of SEL decline with MPS remained similar after adjustment for right striatal volume (adjusted odds ratio = 2.03, 95% CI: 1.16-3.54). CONCLUSION: SEL decline may be faster in those with MPS. Striatal atrophy may be important for declining energy but does not explain the association with MPS.

Declining energy predicts incident mobility disability and mortality risk in healthy older adults.

BACKGROUND: The purpose was to examine whether longitudinal changes in self-reported energy predict incident mobility disability and mortality. We further explored whether changes in energy-related behaviors (physical activity, appetite, or sleep quality) would explain these associations. METHODS: N = 2021 participants from the Health, Aging and Body Composition Study free from mobility disability and with at least three energy assessments from years 2 to 10. MEASUREMENTS: The outcomes were time to first self-reported inability to walk a quarter of a mile (mobility disability) and death. Self-reported energy level (SEL) was a single-item indicator over the prior month, ranging from 0 to 10; person-specific slopes measured whether individuals increased or decreased in SEL across the total follow-up time (mean 7.09 years, +1.72, range 2-8 years). Potential energy-related mediators were baseline and change in self-reported physical activity, appetite, and sleep quality. Covariates were baseline levels and change in demographics, health characteristics and behaviors, tiredness, cognition, mood, and gait speed. RESULTS: A total of 947 developed disability and 567 died over the study follow-up. A one-point change in SEL over the follow-up (or an average 0.125 points/year) was inversely associated with a 35% risk of incident mobility disability (hazard ratio = 0.65, 95% confidence interval [CI] = 0.55, 0.76, p < 0.001) and 33% risk of death (hazard ratio = 0.67, 95% CI = 0.42, 0.87, p = 0.003), independent of covariates. Potential energy-related mediators did not attenuate this association. CONCLUSIONS: In this longitudinal analysis of community-dwelling older adults, energy decline was common and a significant independent predictor of disability risk and mortality.

Geographic disparities in cancer screening and fatalism among a nationally representative sample of US adults.

BACKGROUND: Cancer screening in the USA is suboptimal, particularly for individuals living in vulnerable communities. This study aimed to understand how rurality and racial segregation are independently and interactively associated with cancer screening and cancer fatalism. METHODS: We used data from a nationally representative sample of adults (n=17 736) from National Cancer Institute's Health Information National Trends Survey, 2011-2017, including cancer screening (colorectal, breast, cervical, prostate) among eligible participants and cancer fatalism. These data were linked to county-level metropolitan status/rurality (US Department of Agriculture) and racial segregation (US Census). We conducted multivariable analyses of associations of geographic variables with screening and fatalism. RESULTS: Breast cancer screening was lower in rural (92%, SE=1.5%) than urban counties (96%, SE=0.5%) (adjusted OR (aOR)=0.52, 95% CI 0.31 to 0.87). Colorectal cancer screening was higher in highly segregated (70%, SE=1.0%) than less segregated counties (65%, SE=1.7%) (aOR=1.28, 95% CI 1.04 to 1.58). Remaining outcomes did not vary by rurality or segregation, and these variables did not interact in their associations with screening or fatalism. CONCLUSION: Similar to previous studies, breast cancer screening was less common in rural areas. Contrary to expectations, colorectal cancer screening was higher in highly segregated counties. More research is needed on the influence of geography on cancer screening and beliefs, and how access to facilities or information may mediate these relationships.

Quality Assessment of Tumor Size Data Collection for Pancreatic and Breast Cancer in SEER.

BACKGROUND AND OBJECTIVES: In 2017, the Surveillance, Epidemiology, and End Results (SEER) program piloted a reactive quality audit plan (r-QAP) to analyze Collaborative Stage (CS) tumor size in breast and pancreatic cancer. Preevaluation objectives were to establish procedures and analytic scope for SEER quality audits, cutoffs for data completeness/accuracy, and key decision checkpoints. METHODS: Tumor size data between 2004-2014 were selected from SEER registries for pancreatic and breast cancers, and initially assessed by site and registry for completeness. Further exploration was undertaken via cross tabulation in SEER with the American Joint Committee on Cancer (AJCC) 6th edition derived T data item to evaluate discrepancies between these closely related variables. RESULTS: For both cancer sites, completeness improved between 2004 and 2014, with the proportion of known tumor size values increasing from 60.6% to 79.2% in pancreatic cancer and from 94.0% to 95.9% in breast cancer. Tumor size plausibility categories were established wherein any tumor over 100 mm for pancreatic cancer or over 200 mm for breast cancer were considered highly unlikely. Only 2% of pancreas tumors and 0.1% of breast tumors were implausibly large per site-specific cutoffs. Less than 2% of all tumor size values were potentially discrepant in cross-tabulation with AJCC 6th edition derived T for each site. CONCLUSIONS: Most tumor size values appear to fall within acceptable ranges based on r-QAP activities, and implausibly large tumor size values are rare. Different natural histories and clinical presentation for pancreatic and breast cancer illustrate the need for site-specific cutoffs. Our results indicate that there are no major quality issues in the SEER research database for the CS tumor size data item in either pancreatic or breast cancer.

Gait Characteristics of Age-Related Macular Degeneration Patients.

PURPOSE: To identify potential differences between age-related macular degeneration (AMD) patients and controls in fall-relevant gait characteristics. METHODS: Spatiotemporal gait characteristics using the GAITRite walkway were collected from 29 AMD patients and 20 controls, aged 60 to 90 years, at the Wilmer Eye Institute. Multiple linear regressions, controlling for age, sex, body mass index (BMI), and comorbidities were used to assess associations between gait characteristics and AMD. RESULTS: Study participants were predominantly white (86%) and female (55%). Mean age of the full study population was 73.51 (SD: 8.14) years, and mean BMI was 27.80 (SD: 5.44) kg/m2. Median better-eye acuity (logMAR) was 0.23 (interquartile range [IQR] = 0.18, 0.36) and -0.02 (IQR = -0.08, 0.02), while median binocular log contrast sensitivity was 1.44 (IQR = 1.32, 1.56) and 1.76 (IQR = 1.76, 1.80) for the AMD and control groups, respectively. In multivariable regression models, AMD patients had significantly slower walking speeds (ß = -0.118 m/sec [95% confidence interval (CI): -0.229, -0.007], P = 0.038) and stride velocities (ß = -0.119 m/sec [95% CI: -0.232, -0.007], P = 0.038), and greater double support time (ß = 3.381% of the walk cycle, 95% CI = 1.006, 5.757, P = 0.006) than controls. There were no group differences in base of support, step length, stride length, or gait variability measures. CONCLUSION: AMD patients exhibited many fall-relevant gait characteristics. TRANSLATIONAL RELEVANCE: The finding of fall-relevant gait characteristics suggests that AMD patients may be at a greater risk of falls during ambulation than those without AMD.

Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015.

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world. OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden. METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75. CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.