Association of Brain Magnetic Resonance Imaging Signs With Cognitive Outcomes in Persons With Nonimpaired Cognition and Mild Cognitive Impairment.

Importance: Brain atrophy and vascular lesions contribute to dementia and mild cognitive impairment (MCI) in clinical referral populations. Prospective evidence in older general populations is limited.

Objective: To evaluate which magnetic resonance imaging (MRI) signs are independent risk factors for dementia and MCI.

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

ApoB, small-dense LDL-C, Lp(a), LpPLA activity, and cognitive change.

Objective: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change.

Methods: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A (LpPLA) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, ε4 status, and statin use.

Plasma Metabolites Associated with Brain MRI Measures of Neurodegeneration in Older Adults in the Atherosclerosis Risk in Communities⁻Neurocognitive Study (ARIC-NCS).

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults.

Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam.

Association of Head Injury with Brain Amyloid Deposition: The ARIC-PET Study.

Our objective was to examine associations of head injury with total and regional brain amyloid deposition. We performed cross-sectional analyses of 329 non-demented participants (81 with prior head injury) in the Atherosclerosis Risk in Communities-Positron Emission Tomography (ARIC-PET) Study who underwent florbetapir PET imaging in 2012-2014. A history of head injury was defined by self-report or emergency department/hospitalization International Classification of Diseases, Ninth Revision codes.

Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.

We have previously reported cognitive impairments in both young and old mice, particularly in female mice expressing mouse Arg-61 apoE, with a point mutation to mimic the domain interaction feature of human apoE4, as compared to the wildtype mouse (C57BL/6J) apoE. In this study, we further evaluated water maze performance in the female Arg-61 mice at an additional time point and then investigated related hippocampal cyto-architecture in these young female Arg-61 apoE mice vs. the wildtype mice.

Atrial Fibrillation and Brain Magnetic Resonance Imaging Abnormalities.

Background and Purpose- Atrial fibrillation (AF) is associated with dementia independent of clinical stroke. The mechanisms underlying this association remain unclear. In a community-based cohort, the ARIC study (Atherosclerosis Risk in Communities), we evaluated (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain magnetic resonance imaging (MRI) abnormalities.

Association of Atrial Fibrillation With White Matter Disease.

Background and Purpose- Evidence suggests that atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. White matter disease (WMD) is a potential mechanism linking AF to cognitive impairment. In this study, we explored the association between prevalent AF and WMD.

Cognitive Reserve in Midlife is not Associated with Amyloid-β Deposition in Late-Life.

We examined associations between cognitive reserve and late-life amyloid-β deposition using florbetapir positron emission tomography (PET). We used data from the Atherosclerosis Risk in Communities (ARIC) and ARIC-PET Study. 330 dementia-free participants underwent PET scans.

Longitudinal analysis of epigenome-wide DNA methylation reveals novel smoking-related loci in African Americans.

Changes in DNA methylation may be a potential mechanism that mediates the effects of smoking on physiological function and subsequent disease risk. Given the dynamic nature of the epigenome, longitudinal studies are indispensable for investigating smoking-induced methylation changes over time. Using blood samples collected approximately five years apart in 380 African Americans (mean age 60.

Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study.

Objective: To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline.

Methods: Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2.

Neural correlates of domain-specific cognitive decline: The ARIC-NCS Study.

Objective: To evaluate the association of cognitive declines in the domains of memory, language, and executive function with brain gray matter (GM) volume in old age.

Methods: This was a prospective study of 1,846 participants in the Atherosclerosis Risk in Communities (ARIC) Study who underwent 3T brain MRI scans in 2011 to 2013. Participants were categorized by cognitive domain performance trajectory over the prior 20 years (cut point to define decline: 20th percentile).

Differences in Cardiovascular Mortality Risk among African Americans in the Minnesota Heart Survey: 1985-2015 vs The Atherosclerosis Risk in Communities Study Cohort: 1987-2015.

Geographic differences in cardiovascular disease (CVD) mortality among African Americans (AAs) are well-established, but not well-characterized. Using the Minnesota Heart Survey (MHS) and Atherosclerosis Risk in Communities (ARIC) Study, we aimed to assess whether CVD risk factors drive geographic disparities in CVD mortality among AAs. ARIC risk factors were measured between1987-1989 from a population-based sample of AAs, aged 45 to 64 years, living in Jackson, MS and Forsyth County, NC.

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups.

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus.

Neuroimaging findings in midlife and risk of late-life dementia over 20 years of follow-up.

Objective: To examine the association between neuroimaging features in a predominantly middle-aged cohort and risk of late-life dementia.

Methods: Cerebral MRI was performed on 1,881 individuals with no history of stroke from the Atherosclerosis Risk in Communities Study cohort in 1993 to 1995. White matter hyperintensities (WMH), ventricular size, and sulcal size were graded on a semiquantitative scale, and presence of silent cerebral infarcts was identified.

Central Arterial Stiffness Is Associated With Structural Brain Damage and Poorer Cognitive Performance: The ARIC Study.

Background Central arterial stiffening and increased pulsatility, with consequent cerebral hypoperfusion, may result in structural brain damage and cognitive impairment. Methods and Results We analyzed a cross-sectional sample of ARIC - NCS (Atherosclerosis Risk in Communities-Neurocognitive Study) participants (aged 67-90 years, 60% women) with measures of cognition (n=3703) and brain magnetic resonance imaging (n=1255). Central arterial hemodynamics were assessed as carotid-femoral pulse wave velocity and pressure pulsatility (central pulse pressure).

ERβ agonist alters RNA splicing factor expression and has a longer window of antidepressant effectiveness than estradiol after long-term ovariectomy.

Background: Estrogen therapy (ET), an effective treatment for perimenopausal depression, often fails to ameliorate symptoms when initiated late after the onset of menopause. Our previous work has suggested that alternative splicing of RNA might mediate these differential effects of ET.

Methods: Female Sprague–Dawley rats were treated with estradiol (E2) or vehicle 6 days (early ET) or 180 days (late ET) after ovariectomy (OVX).

Associations of Echocardiography Markers and Vascular Brain Lesions: The ARIC Study.

Background Associations between subtle changes in cardiac and cerebral structure and function are not well understood, with some studies suggesting that subclinical cardiac changes may be associated with markers of vascular brain insult. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) Study (5th ARIC visit; 2011-2013; N=1974) were used to explore relationships between abnormalities of cardiac structure/function and subclinical brain disease and to test specific associations between those cardiac and vascular brain changes that share a common mechanism. In adjusted models white matter hyperintensities were 0.

Retinal signs and risk of incident dementia in the Atherosclerosis Risk in Communities study.

Introduction: The easily-imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia.

Methods: In a population-based study of 12,482 adults aged 50-73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993-1995) with incident all-cause dementia (1993-1995 to 2011-2013) and with etiologic subtype of dementia/mild cognitive impairment (2011-13).

Results: A total of 1259 (10%) participants developed dementia over a mean 15.

Impaired Lung Function, Lung Disease, and Risk of Incident Dementia.

Growing evidence suggests that compromised lung health may be linked to dementia and worsening cognitive ability. To test the hypothesis that impaired lung function or lung disease in midlife is associated with greater risk of incident dementia and mild cognitive impairment (MCI) later in life. A total of 14,184 Atherosclerosis Risk in Communities study participants who underwent spirometry and were asked about lung health (1987-1989) were followed.