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Association of midlife lipids with 20-year cognitive change: A cohort study.

ABSTRACT: 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.

SUBMITTER: Power MC

PROVIDER: S-EPMC5803364 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Association of midlife lipids with 20-year cognitive change: A cohort study.

Power Melinda C MC Rawlings Andreea A Sharrett A Richey AR Bandeen-Roche Karen K Coresh Josef J Ballantyne Christie M CM Pokharel Yashashwi Y Michos Erin D ED Penman Alan A Alonso Alvaro A Knopman David D Mosley Thomas H TH Gottesman Rebecca F RF

Alzheimer's & dementia : the journal of the Alzheimer's Association 20170912 2

<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Elevated total choleste ...[more]

PMID: 28916238

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Project description:ImportanceHypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age.ObjectiveTo evaluate the association between midlife (48-67 years of age) hypertension and the 20-year change in cognitive performance.Design, setting, and participantsThe Atherosclerosis Risk in Communities cohort (1990-1992 through 2011-2013) underwent evaluation at field centers in Washington County, Maryland, Forsyth County, North Carolina, Jackson, Mississippi, and the Minneapolis, Minnesota, suburbs. Of 13 476 African American and white participants with baseline cognitive data, 58.0% of living participants completed the 20-year cognitive follow-up.ExposuresHypertension, prehypertension, or normal blood pressure (BP) at visit 2 (1990-1992) constituted the primary exposure. Systolic BP at visit 2 or 5 (2011-2013) and indication for treatment at visit 2 based on the Eighth Joint National Committee (JNC-8) hypertension guidelines constituted the secondary exposures.Main outcomes and measuresPrespecified outcomes included the 20-year change in scores on the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test and in global cognition.ResultsDuring 20 years, baseline hypertension was associated with an additional decline of 0.056 global z score points (95% CI, -0.100 to -0.012) and prehypertension was associated nonsignificantly with 0.040 more global z score points of decline (95% CI, -0.085 to 0.005) compared with normal BP. Individuals with hypertension who used antihypertensives had less decline during the 20 years than untreated individuals with hypertension (-0.050 [95% CI, -0.003 to -0.097] vs -0.079 [95% CI, -0.156 to -0.002] global z score points). Having a JNC-8-specified indication for initiating antihypertensive treatment at baseline was associated with a greater 20-year decline (-0.044 [95% CI, -0.085 to -0.003] global z score points) than not having an indication. We observed effect modification by race for the continuous systolic BP analyses (P = .01), with each 20-mm Hg increment at baseline associated with an additional decline of 0.048 (95% CI, -0.074 to -0.022) points in global cognitive z score in whites but not in African Americans (decline, -0.020 [95% CI, -0.026 to 0.066] points). Systolic BP at the end of follow-up was not associated with the preceding 20 years of cognitive change in either group. Methods to account for bias owing to attrition strengthened the magnitude of some associations.Conclusions and relevanceMidlife hypertension and elevated midlife but not late-life systolic BP was associated with more cognitive decline during the 20 years of the study. Greater decline is found with higher midlife BP in whites than in African Americans.

Project description:Background:Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. Objective:To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Design:Longitudinal cohort study. Setting:Two ARIC (Atherosclerosis Risk in Communities) study sites with magnetic resonance imaging data (1993 to 1995) and up to 5 cognitive assessments over 20 years. Participants:Stroke-free participants aged 50 years or older. Measurements:Infarctions were categorized as none, smaller only, larger only (3 to 20 mm), or both smaller and larger. Global cognitive Z scores were derived from 3 cognitive tests administered up to 5 times. Mixed-effects models estimated adjusted associations between infarctions and cognitive decline. Results are the average difference in standardized cognitive decline associated with infarctions versus no infarctions. Results:Among 1884 participants (mean age, 62 years; 60% women; 50% black), 1611 (86%) had no infarctions, 50 (3%) had smaller infarctions only, 185 (10%) had larger infarctions only, and 35 (2%) had both. Participants with both smaller and larger infarctions had steeper cognitive decline by more than half an SD (difference, -0.57 SD [95% CI, -0.89 to -0.26 SD]) compared with those who had no infarctions. Amounts of cognitive decline associated with only smaller infarctions and only larger infarctions were similar and were not statistically different from that associated with no infarctions. Limitation:Few participants had only smaller infarctions or both smaller and larger infarctions, and the data lacked counts of smaller infarctions and volumes of white matter hyperintensities. Conclusion:The substantial cognitive decline from middle age associated with having both smaller and larger infarctions, but not larger infarctions alone, suggests that the combination of smaller and larger infarctions may escalate risk for cognitive decline later in life in stroke-free persons. Primary Funding Source:National Institutes of Health.

Project description:BACKGROUND:There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer's disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging. METHODS:We included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (?1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity). FINDINGS:Younger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without. CONCLUSIONS:Resilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms.

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Association of midlife lipids with 20-year cognitive change: A cohort study.

Publications

Association of midlife lipids with 20-year cognitive change: A cohort study.

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