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Andrea L.C. Schneider;
Di Zhao;
Pamela L. Lutsey;
Rebecca F. Gottesman;
A. Richey Sharrett;
Andreea M. Rawlings;
Alvaro Alonso;
David Knopman;
Thomas H. Mosley;
Elizabeth Selvin;
Erin D. Michos
Background/Aims: 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with cognitive decline and incident dementia in elderly populations; however, these relationships are susceptible to reverse causation. Less is known about the association of midlife 25(OH)D with long-term cognitive decline. Methods: This was a prospective cohort study of 13,044 participants (mean age 57 years at baseline) in the Atherosclerosis Risk in Communities Study. 25(OH)D was measured from serum collected at baseline (1990-1992) using liquid chromatography tandem high-sensitivity mass spectrometry. Cognition was assessed using 3 neuropsychological tests at 3 time points, which were combined into a composite cognitive Z-score. Multivariable-adjusted linear mixed-effects models with random intercepts and slopes were used to estimate associations between 25(OH)D and cognitive change over 20 years. Results: Compared to persons with sufficient 25(OH)D (≥30 ng/mL), those with deficient (< 20 ng/mL) and intermediate (20-< 30 ng/mL) 25(OH)D concentrations had similar cognitive decline in composite cognitive Z-scores (deficient versus sufficient: -0.035 [95% CI -0.104 to 0.033] and intermediate versus sufficient: -0.029 [95% CI -0.080 to 0.023]). Conclusions: Lower concentrations of 25(OH)D measured in midlife were not significantly associated with more rapid cognitive decline over a 20-year follow-up period. The results of this prospective study are less susceptible to reverse causation than prior studies.
Introduction: Diabetes is prospectively associated with cognitive decline. Whether lower cognitive function and worse brain structure are prospectively associated with incident diabetes is unclear. Methods: We analyzed data for 10,133 individuals with cognitive function testing (1990–1992) and 1212 individuals with brain magnetic resonance imaging (1993–1994) from the Atherosclerosis Risk in Communities cohort. We estimated hazard ratios for incident diabetes through 2014 after adjustment for traditional diabetes risk factors and cohort attrition. Results: Higher level of baseline cognitive function was associated with lower risk for diabetes (per 1 standard deviation, hazard ratio = 0.94; 95% confidence interval = 0.90, 0.98). This association did not persist after accounting for baseline glucose level, case ascertainment methods, and cohort attrition. No association was observed between any brain magnetic resonance imaging measure and incident diabetes. Discussion: This is one of the first studies to prospectively evaluate the association between both cognitive function and brain structure and the incidence of diabetes.
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Alvaro Alonso;
David S. Knopman;
Rebecca F. Gottesman;
Elsayad Z. Soliman;
Amit Shah;
Wesley T. O'Neal;
Faye L. Norby;
Thomas H. Mosley;
Lin Y. Chen
BACKGROUND: Atrial fibrillation (AF) has been associated with faster cognitive decline and increased dementia risk. Factors associated with dementia in patients with AF have been seldom studied. METHODS AND RESULTS: We studied 6432 individuals from the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). In 2011 to 2013, participants underwent a physical exam, echocardiography, detailed cognitive assessments, and a subset, brain magnetic resonance imaging. Dementia and mild cognitive impairment (MCI), as well as etiology of MCI/dementia, Alzheimer's disease-related or vascular, were adjudicated by an expert panel. AF was defined by study ECGs and past hospitalizations. We used logistic regression to estimate odds ratios and 95% CI of MCI/dementia by AF status and to assess cross-sectional correlates of MCI/dementia in patients with AF. Among 6432 participants, 611 (9.5%) had prevalent AF. AF was associated with increased odds of dementia and MCI (odds ratio, 95% CI, 2.25, 1.64-3.10, and 1.28, 1.04-1.56, respectively). Prevalence of Alzheimer's disease-related MCI/dementia and vascular MCI/dementia were higher in participants with AF than without AF (odds ratio, 95% CI, 1.29, 1.04-1.61, and 1.50, 0.99-2.25, respectively). In multivariable analyses, older age, lower body mass index, diabetes mellitus, stroke, and APOE genotype were associated with dementia prevalence in participants with AF. In models evaluating MCI/dementia subtypes, diabetes mellitus was associated with Alzheimer's disease-related MCI/dementia, whereas male sex and stroke were risk factors for vascular MCI/dementia. CONCLUSIONS: In a large, community-based study, AF was associated with higher prevalence of MCI and dementia. Controlling cardiometabolic risk factors is a potential target for prevention of adverse cognitive outcomes in AF patients.
by
Melinda C. Power;
Andreea Rawlings;
A. Richey Sharrett;
Karen Bandeen-Roche;
Josef Coresh;
Christie Ballantyne;
Yashashwi Pokharel;
Erin D. Michos;
Alan Penman;
Alvaro Alonso;
David Knopman;
Thomas H. Mosley;
Rebecca F. Gottesman
Introduction Existing studies predominantly consider the association of late-life lipid levels and subsequent cognitive change. However, midlife rather than late-life risk factors are often most relevant to cognitive health. Methods We quantified the association between measured serum lipids in midlife and subsequent 20-year change in performance on three cognitive tests in 13,997 participants of the Atherosclerosis Risk in Communities study. Results Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides were associated with greater 20-year decline on a test of executive function, sustained attention, and processing speed. Higher total cholesterol and triglycerides were also associated with greater 20-year decline in memory scores and a measure summarizing performance on all three tests. High-density lipoprotein cholesterol was not associated with cognitive change. Results were materially unchanged in sensitivity analyses addressing informative missingness. Discussion Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides in midlife were associated with greater 20-year cognitive decline.
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Pamela L. Lutsey;
Jeffrey R. Misialek;
Thomas H. Mosley;
Rebecca F. Gottesman;
Naresh M. Punjabi;
Eyal Shahar;
Richard MacLehose;
Rachel P. Ogilvie;
David Knopman;
Alvaro Alonso
Introduction This study tested the hypotheses that late-midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia over 15 years of follow-up. Methods A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in-home polysomnography (1996–1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996–2012) and (2) a comprehensive neurocognitive examination (2011–2013) with adjudication. Results OSA and sleep duration were not associated with risk of incident dementia. When using adjudicated outcomes, severe OSA (≥30 vs. <5 apnea-hypopnea events/hour) was associated with higher risk of all-cause dementia (risk ratio [95% confidence interval], 2.35 [1.06–5.18]) and Alzheimer's disease dementia (1.66 [1.03–2.68]); associations were attenuated with cardiovascular risk factor adjustment. Sleeping <7 versus 8 to ≤9 hours was associated with higher risk of all-cause dementia (2.00 [1.03–3.86]). Discussion When adjudicated outcome definitions were used, late-midlife OSA and short sleep duration were associated with all-cause and Alzheimer's disease dementia in later life.
by
Pamela L. Lutsey;
Faye L. Norby;
Rebecca F. Gottesman;
Thomas Mosley;
Richard F. MacLehose;
Naresh M. Punjabi;
Eyal Shahar;
Clifford R. Jack, Jr.;
Alvaro Alonso
Background A growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation. Objective We tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54-73 years, would be associated with adverse brain morphology at ages 67-89 years. Methods Included in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996-1998 and brain MRI scans about 15 years later (2012-2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/ severe (≥15.0 events/hour), mild (5.0-14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to ≥8, 8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer's disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias. Results At the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes. Conclusions In this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer's disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations.
by
Hector M. Gonzalez;
Wassim Tarraf;
Kimystian Harrison;
B. Gwen Windham;
Jonathan Tingle;
Alvaro Alonso;
Michael Griswold;
Gerardo Heiss;
David Knopman;
Thomas H. Mosley
Introduction: The aim was to examine associations between midlife cardiovascular health (CVH) and 20-year cognitive decline among blacks and whites.
Methods: Midlife CVH metrics (American Heart Association's Life's Simple 7) were calculated and examined in relation to midlife and 20-year change in cognitive function among 13,270 whites and blacks from the Atherosclerosis Risk in Communities Cohort Study. We used linear mixed models to estimate adjusted associations of midlife CVH with midlife cognitive status and change. Results: Higher midlife (Life's Simple 7) scores and individual metrics, particularly blood pressure and glucose, were associated with better midlife cognition and reduced 20-year decline. Midlife CVH 20-year neuroprotection was more pronounced among whites than blacks.
Discussion: Better midlife CVH was associated with higher midlife and reduced decline in cognitive function 20 years later. However, the benefits of midlife CVH on cognition were stronger for whites than for blacks. Our findings suggest that improved midlife CVH may promote enduring cognitive health.
Background: There are no agreed-upon variables for predicting progression from unimpaired cognition to amnestic mild cognitive impairment (aMCI), or from aMCI to Alzheimer's disease (AD). Objective: Use ADNI data to develop a 'Framingham-like' prediction model for a 4-year period. Methods: We developed models using the strongest baseline predictors from six domains (demographics, neuroimaging, CSF biomarkers, genetics, cognitive tests, and functional ability). We chose the best predictor from each domain, which was dichotomized into more versus less harmful. Results: There were 224 unimpaired individuals and 424 aMCI subjects with baseline data on all predictors, of whom 37 (17%) and 150 (35%) converted to aMCI and AD, respectively, during 4 years of follow-up. For the unimpaired, CSF tau/Aβ ratio, hippocampal volume, and a memory score predicted progression. For those aMCI at baseline, the same predictors plus APOE4 status and functional ability predicted progression. Demographics and family history were not important predictors for progression for either group. The fit statistic was good for the unimpaired-aMCI model (C-statistic 0.80) and very good for the aMCI-AD model (C-statistic 0.91). Among the unimpaired, those with no harmful risk factors had a 4-year predicted 2% risk of progression, while those with the most harmful risk factors had a predicted 35% risk. The aMCI subjects with no harmful risk factors had a predicted 1% risk of progression those with all six harmful risk factors had a predicted 90% risk. Conclusion: Our parsimonious model accurately predicted progression from unimpaired to aMCI with three variables, and from aMCI to AD with five variables.
by
Iris Yuefan Shao;
Melinda C. Power;
Thomas Mosley;
Clifford Jack;
Rebecca F. Gottesman;
Lin Y. Chen;
Faye L. Norby;
Elsayed Z. Soliman;
Alvaro Alonso
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.
Methods:
We performed a cross-sectional analysis of participants attending the ARIC-NCS (Atherosclerosis Risk in Communities-Neurocognitive Study) in 2011 to 2013 who underwent brain magnetic resonance imaging. AF was ascertained from study visit electrocardiograms or prior hospitalization codes. Extent of WMD was defined by measures of white matter (WM) microstructural integrity and WM hyperintensity volume. Multivariable linear regression models were used to assess the association between AF and WMD.
Results:
Among 1899 participants (mean age, 76 years; 28% black; 60% women), 133 (7%) had prevalent AF. After multivariable adjustment, differences between participants with and without AF were -0.001 (95% CI, -0.006 to 0.004) for global WM fractional anisotropy, 0.031×10-4 mm2/s (95% CI, -0.075 to 0.137) for global WM mean diffusivity, and 0.08 mm3 (95% CI, -0.14 to 0.30) for WM hyperintensity volume.
Conclusions:
The results suggest that there is no association between prevalent AF and WMD.
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, we evaluated: (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain MRI abnormalities.
METHODS
The longitudinal analysis included 963 participants (mean age, 73±4.4 years, 62% women, 51% black) without prevalent stroke or AF who underwent a brain MRI in 1993–1995 and a second MRI in 2004–2006 (mean, 10.6±0.8 years). Outcomes included subclinical cerebral infarctions (SCI), sulcal size, ventricular size, and, for the cross-sectional analysis, white matter hyperintensity (WMH) volume and total brain volume (TBV).
RESULTS
In the longitudinal analysis, 29 (3.0%) participants developed AF after the first brain MRI. Those who developed AF had higher odds of increase in SCIs (OR, 3.08; 95% CI, 1.39–6.83), worsening sulcal grade (OR, 3.56; 95% CI, 1.04–12.2), and worsening ventricular grade (OR, 9.34; 95% CI 1.24–70.2). In cross-sectional analysis, of 969 participants, 35 (3.6%) had prevalent AF at the time of the 2004–2006 MRI scan. Those with AF had greater odds of higher sulcal (OR, 3.9; 95% CI, 1.7–9.1) and ventricular grade (OR, 2.4; 95% CI, 1.0–5.7) after multivariable adjustment, and no difference in WMH or TBV.
CONCLUSION
AF is independently associated with increase in SCI and worsening sulcal and ventricular grade—morphological changes associated with aging and dementia. More research is needed to define the mechanisms underlying AF-related neurodegeneration.