Alonso, Álvaro

AbstractIntroductionExisting 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.MethodsWe 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.ResultsElevated 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.DiscussionElevated total cholesterol, low‐density lipoprotein cholesterol, and triglycerides in midlife were associated with greater 20‐year cognitive decline.

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.

Abstract 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.

Objective To assess the risk of liver injury hospitalisation in patients with atrial fibrillation (AF) after initiation of direct oral anticoagulants (DOACs) or warfarin and to determine predictors of liver injury hospitalisation in this population. Methods We studied 113 717 patients (mean age 70, 39% women) with AF included in the MarketScan Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after 4 November 2011, followed through 31 December 2014. Of these, 56 879 initiated warfarin, 17 286 initiated dabigatran, 30 347 initiated rivaroxaban and 9205 initiated apixaban. Liver injury hospitalisation and comorbidities were identified from healthcare claims. Results During a median follow-up of 12 months, 960 hospitalisations with liver injury were identified. Rates of liver injury hospitalisation (per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban) and 5.6 (apixaban). After multivariable adjustment, liver injury hospitalisation rates were lower in initiators of DOACs compared with warfarin: HR (95% CI) of 0.57 (0.46 to 0.71), 0.88 (0.75 to 1.03) and 0.70 (0.50 to 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (vs. warfarin). Compared with dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalisation (HR 1.56, 95% CI 1.22 to 1.99). In addition to type of anticoagulant, prior liver, gallbladder and kidney disease, cancer, anaemia, heart failure and alcoholism significantly predicted liver injury hospitalisation. A predictive model including these variables had adequate discriminative ability (C-statistic 0.67, 95% CI 0.64 to 0.70). Conclusions Among patients with non-valvular AF, DOACs were associated with lower risk of liver injury hospitalisation compared with warfarin, with dabigatran showing the lowest risk.

AbstractIntroductionThe objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a mostly African‐American cohort.MethodsWe repeatedly measured 188 phospholipids/metabolites in plasma samples of 221 participants of the Atherosclerosis Risk in Communities study, 97% African American, who were followed between 2004–2006 and 2011–2013.ResultsAfter a mean follow‐up of 7.3 years, 77 were classified as having MCI and 18 as having dementia. Our study failed to replicate previous findings in this mostly African American cohort, in that the 10 phospholipids/metabolites only achieved a C statistic/AUC of 0.609 in predicting development of MCI or dementia (compared to 0.96) and 0.607 in distinguishing normal from MCI or dementia at the follow‐up visit.ConclusionA panel of 10 phospholipids/metabolites previously associated with incident dementia was not predictive of MCI or dementia in an independent cohort.

Background While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce. Methods and Results Olmsted County, MN residents with incident atrial fibrillation or atrial flutter (collectively referred to as AF ) from 2000 to 2010 were identified. Cox regression determined associations of year of AF diagnosis with ischemic stroke and transient ischemic attack ( TIA ) occurring through 2013. Among 3247 AF patients, 321 (10%) had an ischemic stroke/ TIA over a mean of 4.6 years (incidence rate [95% CI ] per 100 person‐years: 2.14 [1.91–2.38]). Two hundred thirty‐nine (7%) of 3265 AF patients experienced an ischemic stroke (incidence rate: 1.54 [1.35–1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95% CI ] per year of AF diagnosis: 1.00 [0.96–1.04] for ischemic stroke/ TIA ; 1.01 [0.96–1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after AF diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95% CI ] per year of AF diagnosis: 1.06 [0.97–1.15] for ischemic stroke/ TIA ; 1.08 [0.98–1.20] for ischemic stroke only). Conclusions Strokes/ TIA s are frequent after AF , occurring in 10% of patients after 5 years of follow‐up. The occurrence of stroke/ TIA did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications.

AbstractIntroductionPhospholipids are altered in brains of patients with dementia and some studies suggest their plasma levels may be useful in the detection of mild cognitive impairment (MCI) and dementia.MethodsWe measured 188 plasma metabolites in participants who underwent a detailed neuropsychological assessment and classified as normal (n = 153), MCI (n = 145), or dementia (n = 143) by expert adjudication.ResultsAmong 10 phospholipids recently implicated as altered in dementia, higher concentration of PC aa C36:6 was significantly associated with decreased prevalence of dementia (odds ratio = 0.71, 95% confidence interval = 0.50–1.00 per 1−SD increase). Adding these phospholipids to a model including multiple predictors of dementia led to only minimal improvement in detection (C statistic changed from 0.702 to 0.71).DiscussionSome phospholipids and metabolites were altered in MCI and dementia but cross‐sectional association was relatively weak and did not improve detection of MCI and dementia beyond information provided by clinical variables.