Dataset Information

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults.

ABSTRACT: Serum GDF15 levels are correlated with multiple neurodegenerative diseases. Few studies have tested this marker's association with middle-aged cognitive performance over time, and whether race affects this association is unknown. We examined associations of initial serum GDF15 concentrations with longitudinal cognitive performance, spanning domains of global mental status, visual and verbal memory, attention, fluency, and executive function in a sub-sample of adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 776, Age_v1:30-66y, 45.6 % male, 57.0 % African American, 43.0 % below poverty). This analysis consisted of mixed-effects regression models applied to the total selected sample, while also stratifying the analyses by race in the main analyses and further stratifying by sex, age group and poverty status in an exploratory analysis. Our main findings, which passed multiple testing and covariate-adjustment, indicated that GDF15 was associated with poorer baseline performance on several cognitive tests, including animal fluency [overall sample: (Model 1: γ₀ ± SE: -0.664 ± 0.208, P < 0.001; Model 2, γ₀ ± SE: -0.498 ± 0.217, P < 0.05)]. Among White adults, GDF15 was linked to poorer performance on a brief test of attention (Model 1: γ₀ ± SE: -0.426 ± 0.126, P < 0.001; Model 2, γ₀ ± SE: -0.281 ± 0.139, P < 0.05); and Trailmaking test, part B (Model 1: γ₀ ± SE: +0.129 ± 0.040, P < 0.001; Model 2, γ₀ ± SE: +0.089 ± 0.041, P < 0.05), the latter being also linked to higher GDF15 among individuals living below poverty. Among women, GDF15 was associated with poor global mental status (Normalized MMSE: Model 1: γ₀ ± SE: -2.617 ± 0.746, P < 0.001; Model 2: γ₀ ± SE: -1.729 ± 0.709, P < 0.05). GDF15 was not associated with decline on any of the 11 cognitive test scores considered in ∼ 4 years of follow-up. In sum, we detected cross-sectional associations between GDF15 and cognition, although GDF15 did not predict rate of change in cognitive performance over time among a sample of middle-aged adults. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC10026559 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults.

Beydoun May A MA Noren Hooten Nicole N Weiss Jordan J Beydoun Hind A HA Georgescu Michael M Freeman David W DW Evans Michele K MK Zonderman Alan B AB

Brain, behavior, and immunity 20221219

Serum GDF15 levels are correlated with multiple neurodegenerative diseases. Few studies have tested this marker's association with middle-aged cognitive performance over time, and whether race affects this association is unknown. We examined associations of initial serum GDF15 concentrations with longitudinal cognitive performance, spanning domains of global mental status, visual and verbal memory, attention, fluency, and executive function in a sub-sample of adults participating in the Healthy ...[more]

PMID: 36549580

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Project description:BackgroundEpidemiological evidence suggests that both anemia and elevated red cell distribution width (RDW) are associated with cognitive impairment. However, the interplay between these 2 predictors has been understudied.ObjectivesWe examined sex- and anemia-specific associations between RDW and cognitive performance among urban adults in the United States.MethodsData from the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study (Baltimore, MD; participants aged 30-65 y at baseline, ∼59% African-American, 45% men) were used. Participants were selected based on the completion of 11 cognitive tasks at baseline (2004-2009) and follow-up (2009-2013) visits (mean time between visits: 4.64 ± 0.93 y) and availability of exposure and covariate data, yielding a sample of between 1526 and 1646 adults out of the initial 3720 adults recruited at baseline. Multiple linear mixed-effects regression models were conducted with RDW as the main exposure of interest and anemia/sex as the key effect modifiers.ResultsOverall, high RDWs were linked to poorer baseline performance on the California Verbal Learning Test (CVLT) List A (per 1 unit increase in RDW %, main effect: γ01 = -0.369 ± 0.114; P = 0.001) and to slower rates of decline on the CVLT Delayed Free Recall (per 1 unit increase in RDW %, RDW × time: γ11 = +0.036 ± 0.013; P = 0.007). Among nonanemic participants, RDWs were consistently associated with poorer baseline performance on the Trailmaking Test, Part A (γ01 = +3.11 ± 0.89; P < 0.001) and on the CVLT List A (γ01 = -0.560 ± 0.158; P < 0.001). Moreover, RDWs were associated with poorer baseline performance on the Brief Test of Attention in the total population (γ01 = -0.123 ± 0.039; P = 0.001) and among men (γ01 = -0.221 ± 0.068; P = 0.001). We did not detect an association between hemoglobin (Hb) and baseline cognitive performance or changes over time.ConclusionsElevated RDW had a consistent cross-sectional association with poor cognitive performance in the domains of verbal memory and attention among the nonanemic group in a sample of middle-aged, urban adults. Anemia and Hb concentrations were not associated with cognition. More longitudinal studies are needed to replicate our findings.

Project description:BackgroundChronic systemic inflammation has been positively associated with structural and functional brain changes representing early markers of Alzheimer's Disease (AD) and cognitive decline. The current study examined associations between systemic inflammation and cognitive performance among African-Americans and Whites urban adults.MethodsParticipants were selected from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (2004-2013, baseline age: 30-64 y, mean ± SD follow-up time of 4.64 ± 0.93 y, N = 189-222, k = 1.5-1.7 observations/participant). Cytokines known to be positively linked to AD incidence among others were tested against cross-sectional and longitudinal cognitive function, stratifying by age group (≤50 y vs. >50 y), sex and race. A series of mixed-effects regression models were conducted, adjusting for key confounders.ResultsAmong key findings, IL1β was positively associated with a faster rate of decline on a test of executive functioning, among older adults (age >50 y, γ11 = +2.49 ± 0.89, p = 0.005), while in the total population, IL-6 was linked to a faster decline on a test of verbal memory (γ11 = -0.011 ± 0.004, p = 0.009). Among younger participants, IL-18 was linked to a poorer performance on a test of attention at baseline (age ≤50 y, γ01 = -0.007 ± 0.0025, p = 0.004) though a slower rate of decline with higher IL-18 was detected for a test of psychomotor speed in older adults (age >50 y, γ11 = +0.0010 ± 0.0004, p = 0.008). Finally, among Whites, unlike among African-Americans, IL-6 was associated with a better baseline performance on two tests of verbal and working memory.ConclusionsCytokines were shown to be associated with age-related cognitive decline among middle-aged and older urban adults in an age group and race-specific manner. Further longitudinal studies are needed to replicate our findings and mediation through relevant biological and psychosocial factors need to be studied as well.

Project description:Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race. Patients/Methods: Among 1,555-1,719 White and African-American urban adults [Agebase: 30-64y, 2004-2013, mean±SD follow-up time(y): 4.64 ± 0.93y], conducted linear mixed-effects regression models were conducted to test associations of inflammatory markers [C-reactive protein, Erythrocyte Sedimentation Rate (ESR), albumin, iron, and an inflammation composite score (ICS)] with longitudinal cognitive performance. Results: Among key findings, CRP was linked to poorer baseline mental status among younger women (≤50y, γ01 = -0.03 ± 0.01, p = 0.002) and poorer attention in older women (>50y, γ01 = -0.024 ± 0.007, p < 0.004) and African-Americans (γ01 = -0.029 ± 0.008, p < 0.001). ESR was related to faster decline on verbal memory among older men (>50y, γ11 = -0.008 ± 0.003, P = 0.009); with poorer performance on attention tests overall (γ01 = -0.010 ± 0.003, P = 0.003) and among African-Americans (γ01 = -0.013 ± 0.004, P = 0.002); on verbal fluency among older women (>50y,γ01 = -0.037 ± 0.013, P = 0.004) and on executive function: overall (γ01 = +0.62 ± 0.21, P = 0.004), older men (>50y, γ01 = +1.69 ± 0.53, P = 0.001) and African-Americans (γ01 = +0.84 ± 0.28, P = 0.002). Albumin was linked to slower attention decline among older men (>50y, γ11 = +0.329 ± 0.103, P = 0.009), over-time improvement in executive function overall (γ11 = -6.00 ± 2.26, P = 0.008), and better baseline psychomotor speed among African-Americans (γ01 = +0.56 ± 0.19, P = 0.003). Finally, ICS predicted faster decline on visual memory/visuo-constructive abilities among older men (>50y, γ11 = +0.17 ± 0.06, p = 0.003). Conclusion: In sum, strong associations between systemic inflammation and longitudinal cognitive performance were detected, largely among older individuals (>50y) and African-Americans. Randomized trials targeting inflammation are warranted.

Dataset Information

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults.

Publications

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults.

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