Publications by authors named "Mosley T"

Introduction: Few studies have characterized the association of olfaction with dementia in detail across diverse sociodemographic subgroups.

Methods: We examined the association of one-time-point olfactory status with incident dementia overall and by age, race, sex, and apolipoprotein E (APOE) ε4 status (n = 4470, mean age: 75 ± 5 years, 21% Black), and 5-year olfactory change with incident dementia (n = 2658) in the community-based Atherosclerosis Risk in Communities (ARIC) study.

Results: Compared to good olfaction, moderate olfaction (hazard ratio [HR]: 1.

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This study investigated the relationship between olfactory impairment and frailty among 5,231 (mean age 75.3 (SD 5.0), 59% women, 22% Black) participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort located in the U.

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Objective: Traumatic Brain Injury (TBI) may contribute additional complexity to the clinical picture of mild behavioral impairment (MBI). MBI, a behavioral analog to mild cognitive impairment (MCI), is comprised of five neuropsychiatric domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. We investigated (1) if cross-sectional associations of cognitive status with MBI symptoms differ by TBI status and (2) if prospective associations of MBI domain positivity with incident dementia risk differ by TBI status.

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Background: Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

Methods: We included 5799 older adults with no history of stroke at baseline from 2011 to 2013 (75.

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Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.

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Background: Since older adults spend significant time in their neighborhood environment, environmental factors such as neighborhood socioeconomic disadvantage, high racial segregation, low healthy food availability, low access to recreation, and minimal social engagement may have adverse effects on cognitive function and increase susceptibility to dementia. DNA methylation, which is associated with neighborhood characteristics as well as cognitive function and white matter hyperintensity (WMH), may act as a mediator between neighborhood characteristics and neurocognitive outcomes.

Methods: In this study, we examined whether DNA methylation in peripheral blood leukocytes mediates the relationship between neighborhood characteristics and cognitive function (N = 542) or WMH (N = 466) in older African American (AA) participants without preliminary evidence of dementia from the Genetic Epidemiology Network of Arteriopathy (GENOA).

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Objective: To examine associations of traumatic brain injury (TBI) with self-reported and clinical measures of hearing function.

Setting: Four US communities.

Participants: A total of 3176 Atherosclerosis Risk in Communities Study participants who attended the sixth study visit in 2016-2017, when hearing was assessed.

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Aim: Create an ECG-based model to predict dementia and compare its performance with the existing Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) model.

Methods And Results: Participants without prevalent dementia in the Atherosclerosis Risk in Communities study were studied. Visit 4 (V4) (1996-98, mean age, 62 years) and V5 (2011-13, mean age, 75 years) were used as baselines.

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Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).

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Background And Purpose: Lower left atrial (LA) function is associated with higher dementia risk and may be mechanistically linked through vascular brain injury, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities study, we assessed the cross-sectional association between LA function and brain magnetic resonance imaging (MRI) markers of vascular brain injury.

Methods: We included 1488 participants who were free of prevalent dementia, stroke, or atrial fibrillation and who underwent a two-dimensional echocardiogram and brain MRI in 2011-2013 (mean [± standard deviation] age 76 [± 5] years, 60% female, 27% Black).

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Background: White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low-cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI-only screening design in a hypothetical clinical trial.

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Background And Objectives: Race and ethnicity are proxy measures of sociocultural factors that influence cognitive test performance. Our objective was to compare different regression-based cognitive normative models adjusting for demographics and different combinations of easily accessible/commonly used social determinants of health (SDoH) factors, which may help describe cognitive performance variability historically captured by ethnoracial differences.

Methods: We performed cross-sectional analyses on data from Black and White participants without mild cognitive impairment/dementia in the Atherosclerosis Risk in Communities Study who attended visit 5 in 2011-2013.

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Article Synopsis
  • - White matter hyperintensities indicate damage in the brain's white matter, which can lead to brain shrinkage and is linked to dementia; a study of over 51,000 people found that larger volumes of these hyperintensities correspond to thinner brain cortex.
  • - Researchers identified 20 significant genetic loci related to white matter hyperintensities that affect genes involved in brain cell types known to support vascular health and neuronal function; some of these genes play roles in processes like axonal structure and transport within the brain.
  • - The genetic traits tied to white matter issues were linked to cardiovascular health, neurodegeneration markers, and poorer cognitive performance, with a polygenic risk score effectively predicting dementia risk in a separate large
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Article Synopsis
  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort.

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Article Synopsis
  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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Background: Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized.

Methods: Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines.

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Background: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Study was designed to determine the effects of a best-practice hearing intervention on cognitive decline among community-dwelling older adults. Here, we conducted a secondary analysis of the ACHIEVE Study to investigate the effect of hearing intervention on self-reported communicative function.

Methods: The ACHIEVE Study is a parallel-group, unmasked, randomized controlled trial of adults aged 70-84 years with untreated mild-to-moderate hearing loss and without substantial cognitive impairment.

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Article Synopsis
  • Neurofilament light chain (NfL) levels serve as a key biomarker for neuro-axonal damage in neurodegenerative disorders, and understanding the genetics behind these levels can reveal important molecular mechanisms.
  • A meta-analysis of genome-wide association studies identified significant genetic loci associated with blood NfL levels in both European and African American populations, highlighting two key regions.
  • The study also indicated that a higher polygenic risk score for NfL correlates with increased levels of other neurodegenerative biomarkers and suggests lower kidney function may lead to elevated NfL levels in the blood.
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  • The study investigates how mid-life social relationships influence the link between cerebral small vessel disease (CSVD) markers seen in MRI scans and the risk of developing dementia in older adults.
  • Researchers evaluated participants from the ARIC Study, examining their social support and isolation, and then later assessed CSVD measures and dementia cases over time.
  • Results indicated that poor social relationships intensified the association between white matter hyperintensity volume and dementia risk, with a notably higher hazard ratio for those with weak social ties compared to those with strong relationships.
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Article Synopsis
  • Olfactory dysfunction is an early indicator of neurodegenerative diseases and is linked to higher mortality in older adults, but its genetic causes are not well understood.
  • A genome-wide association study (GWMA) involving over 22,000 participants of European ancestry and additional individuals of African ancestry identified a significant genetic locus associated with olfactory dysfunction.
  • The study found that variations in genes related to olfactory receptors also correlate with various health conditions, including kidney function and cardiovascular disease, suggesting that smell loss may have broader health implications.
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Background: Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort.

Methods: We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities.

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Article Synopsis
  • Plasma biomarkers may help identify Alzheimer’s disease and the need for further research across diverse populations and age groups.
  • The study involved 1,525 participants from the Atherosclerosis Risk in Communities (ARIC) study, measuring biomarkers in midlife and late life to assess changes and associations with dementia.
  • Results showed a decline in the Aβ42:Aβ40 ratio and increases in p-tau181, neurofilament light (NfL), and GFAP, indicating a link between these changes and the development of dementia in the participants.
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Introduction: There is limited evidence regarding the rate of long-term cognitive decline after traumatic brain injury (TBI) among older adults.

Methods: In this prospective cohort study, time-varying TBI was defined by self-report and International Classification of Disease diagnostic codes. Cognitive testing was performed at five visits over 30 years and scores were combined into a global cognition factor score.

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