Wruck, Lisa

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.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by impairment in memory, behavioral changes, and gradual loss of autonomy. Since there is a long latent period prior to diagnosis, the aim of this study was to determine whether twenty single nucleotide polymorphisms identified in genome‐wide association analyses of AD are associated with cognitive change in 8,320 white and 2,039 African‐American middle‐aged adults enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), Digit Symbol Substitution Test (DSST; processing speed), and Word Fluency Test (WFT; executive function). General linear models were used to assess mean differences in 6‐year change in test scores among individuals categorized by genotype after adjusting for age, gender, and years of education. Addition of the minor allele for rs670139 (MS4A4E), rs9331896 (CLU), and rs12155159 (NME8) was nominally associated with change on the DWRT, DSST, and WFT, respectively, in whites. The ZCWPW1(rs1476679) andCDS33(rs3865444) variants were nominally associated with change on the DWRT and WFT in African‐Americans. For rs670139 and rs9331896 the association was only significant in individuals bearing at least oneAPOEϵ4 allele in stratified analyses. An unweighted genetic risk score aggregating the risk alleles for 15 polymorphisms was not associated with change in cognitive function. Although the AD‐associated genetic variants appear to have small effects on early cognitive change, replication will be required to establish whether there is a discernible influence on cognitive status in midlife. © 2016 Wiley Periodicals, Inc.

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.

AbstractIntroductionThe impact of blood pressure on brain volumes may be time‐dependent or pattern‐dependent.MethodsOf 1678 participants from the Atherosclerosis Risk in Communities Neurocognitive Study, we quantified the association between measures and patterns of blood pressure over three time points (∼24 or ∼15 years prior and concurrent with neuroimaging) with late life brain volumes.ResultsHigher diastolic blood pressure ∼24 years prior, higher systolic and pulse pressure ∼15 years prior, and consistently elevated or rising systolic blood pressure from ∼15 years prior to concurrent with neuroimaging, but not blood pressures measured concurrent with neuroimaging, were associated with smaller volumes. The pattern of hypertension ∼15 years prior and hypotension concurrent with neuroimaging was associated with smaller volumes in regions preferentially affected by Alzheimer's disease (e.g., hippocampus: −0.27 standard units, 95% CI: −0.51, −0.03).DiscussionHypertension 15 to 24 years prior is relevant to current brain volumes. Hypertension followed by hypotension appears particularly detrimental.

AbstractIntroductionWe examined prevalence of mild cognitive impairment (MCI) and dementia in the Atherosclerosis Risk in Communities (ARIC) Neurocognitive study.MethodsBeginning in June, 2011, we invited all surviving ARIC participants to undergo cognitive, neurologic, and brain imaging assessments to diagnose MCI or dementia and assign an etiology for the cognitive disorder.ResultsOf 10,713 surviving ARIC participants (age range, 69–88 years), we ascertained cognitive diagnoses in 6471 in person, 1966 by telephone interviews (participant or informant), and the remainder by medical record review. The prevalence of dementia was 9.0% and MCI 21%. Alzheimer's disease (AD) was the primary or secondary etiology in 76% of dementia and 75% of MCI participants. Cerebrovascular disease was the primary or secondary etiology in 46% of dementia and 32% of MCI participants.DiscussionMCI and dementia were common among survivors from the original ARIC cohort. Nearly 30% of the ARIC cohort received diagnoses of either dementia or MCI, and for the majority of these individuals, the etiologic basis was attributed to AD.

Background and Purpose— The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that the cerebral cortical volume mediated these relationships. Methods— Total of 1906 nondemented participants (59% women; 25% African–American; mean age, 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MRI for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined the associations of cognitive domain outcomes with cerebral volumes (hippocampus and separate groups of posterior and frontal cortical regions of interest) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated the associations between cerebrovascular imaging features and cognition. Results— In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function. In mediation analyses, WMH and infarct associations on psychomotor speed/executive function were significantly attenuated, but not abolished, by the inclusion of the posterior cortical regions of interest volume in the models, and the infarcts on psychomotor speed/executive function association were attenuated, but not abolished, by inclusion of the frontal cortical regions of interest volume. Conclusions— Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are 1 candidate for such a clinically covert process.

Background Atrial fibrillation ( AF ) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF ‐related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study. Methods and Results Participants with incident AF enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF , respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF , respectively. Most utilization among AF patients was attributable to non‐ AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95% CI : 3.41 to 6.16) for those with AF versus those without AF . The association between AF and healthcare utilization was similar among men and women and among white and black participants. Conclusions Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease –related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities.