Serum total tau, neurofilament light, and glial fibrillary acidic protein are associated with mortality in a population study.

BACKGROUND: Total tau (t-tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that may indicate greater risk of poor outcomes in age-related conditions, including mortality. Health disparities experienced by some racial minority subgroups may influence biomarker expression and effects on longevity. We aimed to examine (a) associations of serum t-tau, NfL, and GFAP with overall and cardiovascular mortality and (b) differences in associations by racial background. METHODS: Data came from 1327 older participants from the Chicago Health and Aging Project (CHAP), a longitudinal population-based study. Cox proportional hazards regression models were used to examine associations between concentrations of serum t-tau, NfL, and GFAP biomarker(s) and mortality (overall/cardiovascular mortality based on age at death). Interaction terms were used to examine differences between African-American and European-American participants. Models were adjusted for age, sex, education, the APOE-ε4 allele, body mass index, chronic health conditions, and cognitive and physical functioning. RESULTS: Models showed that fivefold higher concentrations of t-tau (HR = 1.46, 95% CI: 1.27, 1.68), NfL (HR = 2.13, 95% CI: 1.76, 2.58), and GFAP (HR = 1.43, 95% CI: 1.08, 1.90) were separately associated with increased risk of overall mortality, with higher risk in African Americans in t-tau or NfL. In models with all biomarkers, NfL (HR = 2.17, 95% CI: 1.65, 2.85) was associated with risk of overall mortality, with racial differences in t-tau. Higher concentrations of t-tau (HR = 1.32, 95% CI: 1.02, 1.70), NfL (HR = 1.95, 95% CI: 1.40, 2.72), and GFAP (HR = 1.87, 95% CI: 1.18, 2.98) were separately associated with risk of cardiovascular mortality, with racial differences in t-tau, NfL, or GFAP. In combined models, NfL (HR = 1.73, 95% CI: 1.08, 2.78) was associated with cardiovascular mortality. CONCLUSIONS: Serum t-tau, NfL, and GFAP may be early indicators for mortality outcomes among older adults, with racial differences among associations.

Population estimate of people with clinical Alzheimer's disease and mild cognitive impairment in the United States (2020-2060).

INTRODUCTION: The estimate of people with clinical Alzheimer's disease (AD) and mild cognitive impairment provides an understanding of the disease burden. METHODS: We estimated people with cognitive impairment using a quasibinomial regression model in 10,342 participants with cognitive test scores. RESULTS: The 2020 US Census-adjusted prevalence of clinical AD was 11.3% (95% confidence interval [CI] = 10.7-11.9): 10.0% among non-Hispanic Whites, 14.0% among Hispanics, and 18.6% among non-Hispanic Blacks. We estimate that in 2020, 6.07 (95% CI = 5.75-6.38) million people were living with clinical AD, which increases to 13.85 (95% CI = 12.98-14.74) million in 2060, 423% higher among Hispanics, 192% higher among Blacks, and 63% higher among Whites. However, there are predicted to be more significant increases in later years among those over 85 and women compared to men. DISCUSSION: The number of people with clinical AD will increase as the "baby boom" generation reaches older ages, exerting a strong upward influence on disease burden.

Impact of Femoroacetabular Impingement Morphology on Gait Assessment in Symptomatic Patients.

BACKGROUND: Gait is abnormal in patients with femoroacetabular impingement (FAI). To date, studies have not correlated radiographic FAI morphology with gait abnormalities. HYPOTHESIS: Gait abnormalities in FAI patients will be associated with radiographic FAI morphology. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: Patients with symptomatic FAI (n = 20) underwent radiographic and gait analysis. Exclusion criteria included previous injuries or surgeries to the lower extremities or lumbar spine as well as bilateral symptomatic FAI. The alpha angle (AA) and center-edge angle (CEA) were measured on anteroposterior (AP) pelvis, Dunn lateral, and false-profile radiographs, and inter- and intraobserver variability was determined. Motion analysis techniques were used to obtain gait data including 3-dimensional kinematic and kinetic data. Descriptive analysis was performed using Spearman correlations for morphologic measurements. A stepwise regression model was used to examine the association of gait measures with AA and CEA. RESULTS: Intraobserver agreement for the AA and CEA was 0.92 (CI, 0.80-0.97) and 0.90 (CI, 0.76-0.96), while interobserver agreement for the angles was 0.96 (CI, 0.89-0.98) and 0.96 (CI, 0.90-0.98), respectively. Descriptive analysis suggested correlations between AA and peak external hip and knee external rotation moments, maximum ankle flexion angle, and ankle range of motion (range, -0.51 to 0.42; P < 0.0001). The CEA correlated with stride, peak external ankle eversion and inversion moments, peak external knee extension moment, and peak external hip flexion moment (range, -0.44 to 0.51; P < 0.0001). We found that gait variables accounted for a large amount of variation in AA (8 variables accounted for 87% variation) and in CEA (7 variables accounted for 82% variation). CONCLUSION: Lower extremity gait parameters correlate highly with radiographic FAI morphology in symptomatic FAI patients. CLINICAL RELEVANCE: Gait abnormalities are present in FAI patients and may be a useful measure in outcome studies.

Association of cognitive functioning, incident stroke, and mortality in older adults.

BACKGROUND AND PURPOSE: Stroke increases the risk of dementia; however, bidirectional association of incident stroke and cognitive decline below dementia threshold is not well established. Also, both cognitive decline and stroke increase mortality risk. METHODS: A longitudinal population-based cohort of 7217 older adults without a history of stroke from a biracial community was interviewed at 3-year intervals. Cognitive function was assessed using a standardized global cognitive score. Stroke was determined by linkage with Medicare claims, and mortality was ascertained via the National Death Index. We used a Cox model to assess the risk of incident stroke, a joint model with a piecewise linear mixed model with incident stroke as a change point for cognitive decline process, and a time-dependent relative risk regression model for mortality risk. RESULTS: During follow-up, 1187 (16%) subjects had incident stroke. After adjusting for known confounders, lower baseline cognitive function was associated with a higher risk of incident stroke (hazard ratio, 1.61; 95% confidence interval, 1.46-1.77). Cognitive function declined by 0.064 U per year before incident stroke occurrence and 0.122 U per year after stroke, a nearly 1.9-fold increase in cognitive decline (95% confidence interval, 1.78-2.03). Both stroke (hazard ratio, 1.17; 95% confidence interval, 1.08-1.26) and cognitive decline (hazard ratio, 1.90; 95% confidence interval, 1.81-1.98) increased mortality risk. CONCLUSIONS: Baseline cognitive function was associated with incident stroke. Cognitive decline increased significantly after stroke relative to before stroke. Cognitive decline increased mortality risk independent of the risk attributable to stroke and should be followed as a marker for both stroke and mortality.

Racial differences on association of depressive symptoms with combined basic and instrumental activities of daily living.

BACKGROUND: Depressive symptoms are predictive of multiple degenerative diseases in older age adults. However, the association of depressive symptoms with onset and progression of disability have not been studied. METHODS: In a cohort of community-dwelling, older black and white adults, 5,446 initially nondisabled subjects were followed annually for disability between 2000 and 2008. Depressive symptoms were assessed at baseline using a summary measure of 10-item version of the Center for Epidemiologic Survey-Depressive symptoms scale. The disability outcome was based on a summary measure of 13 basic and instrumental activities of daily living, and analyzed using a two-part regression model for onset and progression of disability. RESULTS: During follow-up, 44% of blacks and 35% of whites reported onset of disability. After adjusting for confounders, depressive symptoms were associated with increased odds of disability onset in blacks (odds ratio = 1.12, 95% confidence interval, 1.07-1.18) and whites (odds ratio = 1.21, 95% confidence interval, 1.08-1.36). The odds of disability onset associated with depressive symptoms also increased significantly over time in whites (odds ratio = 1.06, 95% confidence interval, 1.04-1.09), but not in blacks. In addition, depressive symptoms were associated with an increasing rate of progression of disability in whites (rate ratio = 1.08, 95% confidence interval, 1.06-1.09), but not in blacks. CONCLUSIONS: Depressive symptoms increased the risk of onset of disability in blacks and whites. This risk tended to increase over time only among whites. A similar race-specific pattern was observed for time-dependent changes due to depressive symptoms in the rate of progression in disability after onset.