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Dietary copper intake may be associated with cognitive decline and dementia. We used data from 10,269 participants of the Atherosclerosis Risks in Communities Study to study the associations of dietary copper intake with 20-year cognitive decline and incident dementia. Dietary copper intake from food and supplements was quantified using food frequency questionnaires. Cognition was assessed using 3 cognitive tests at study visits; dementia was ascertained at study visits and via surveillance. Multiple imputation by chained equations was applied to account for the missing information of cognitive function during follow-up. Survival analysis with parametric models and mixed-effect models were used to estimate the associations for incident dementia and cognitive decline, respectively. During 20 years of follow-up (1996-1998 to 2016-2017), 1,862 incident cases of dementia occurred. Higher intake of dietary copper from food was associated with higher risk of incident dementia among those with high intake of saturated fat (hazard ratio = 1.49, 95% confidence interval: 1.04, 1.95). Higher intake of dietary copper from food was associated with greater decline in language overall (beta = -0.12, 95% confidence interval: -0.23, -0.02). Therefore, a diet high in copper, particularly when combined with a diet high in saturated fat, may increase the risk of cognitive impairment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study., Design: Prospective cohort study., Setting: Four US communities., Participants: A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively., Measurements: We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable., Results: At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (-.34; 95% confidence interval = -.63 to -.04)., Conclusion: Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353-2361, 2019., (© 2019 The American Geriatrics Society.)

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., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Hypertension is a highly prevalent condition which has been established as a risk factor for cardiovascular and cerebrovascular disease. Although the understanding of the relationship between cardiocirculatory dysfunction and brain health has improved significantly over the last several decades, it is still unclear whether hypertension constitutes a potentially treatable risk factor for cognitive decline and dementia. While it is clear that hypertension can affect brain structure and function, recent findings suggest that the associations between blood pressure and brain health are complex and, in many cases, dependent on factors such as age, hypertension chronicity, and antihypertensive medication use. Whereas large epidemiological studies have demonstrated a consistent association between high midlife BP and late-life cognitive decline and incident dementia, associations between late-life blood pressure and cognition have been less consistent. Recent evidence suggests that hypertension may promote alterations in brain structure and function through a process of cerebral vessel remodeling, which can lead to disruptions in cerebral autoregulation, reductions in cerebral perfusion, and limit the brain's ability to clear potentially harmful proteins such as β-amyloid. The purpose of the current review is to synthesize recent findings from epidemiological, neuroimaging, physiological, genetic, and translational research to provide an overview of what is currently known about the association between blood pressure and cognitive function across the lifespan. In doing so, the current review also discusses the results of recent randomized controlled trials of antihypertensive therapy to reduce cognitive decline, highlights several methodological limitations, and provides recommendations for future clinical trial design.

Background: Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized., Methods: In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25., Results: Among men 51-98 at baseline, higher patella Pb concentration (IQR: 21μg/g) was associated with -0.13 lower baseline MMSE (95% CI: -0.25, -0.004) and faster longitudinal MMSE decline (-0.016 units/year, 95% CI: -0.032, -0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: -0.026, -0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: -0.027, -0.002). We found weaker associations with tibia Pb., Conclusions: Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging., Competing Interests: Description of conflicts of Interest The authors have no conflicts of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied., Methods: We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test., Results: An interquartile range (IQR:14.23μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: -0.11 to -0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: -0.97 to -0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: -0.11, 95%CI: -0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele., Conclusions: Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2016. Published by Elsevier Inc.)

Background: Dementia is a devastating condition typically preceded by a long prodromal phase characterized by accumulation of neuropathology and accelerated cognitive decline. A growing number of epidemiologic studies have explored the relation between air pollution exposure and dementia-related outcomes., Methods: We undertook a systematic review, including quality assessment, to interpret the collective findings and describe methodological challenges that may limit study validity. Articles, which were identified according to a registered protocol, had to quantify the association of an air pollution exposure with cognitive function, cognitive decline, a dementia-related neuroimaging feature, or dementia., Results: We identified 18 eligible published articles. The quality of most studies was adequate to exemplary. Almost all reported an adverse association between at least one pollutant and one dementia-related outcome. However, relatively few studies considered outcomes that provide the strongest evidence for a causal effect, such as within-person cognitive or pathologic changes. Reassuringly, differential selection would likely bias toward a protective association in most studies, making it unlikely to account for observed adverse associations. Likewise, using a formal sensitivity analysis, we found that unmeasured confounding is also unlikely to explain reported adverse associations., Discussion: We also identified several common challenges. First, most studies of incident dementia identified cases from health system records. As dementia in the community is underdiagnosed, this could generate either non-differential or differential misclassification bias. Second, almost all studies used recent air pollution exposures as surrogate measures of long-term exposure. Although this approach may be reasonable if the measured and etiologic exposure windows are separated by a few years, its validity is unknown over longer intervals. Third, comparing the magnitude of associations may not clearly pinpoint which, if any, pollutants are the probable causal agents, because the degree of exposure misclassification differs across pollutants. The epidemiologic evidence, alongside evidence from other lines of research, provides support for a relation of air pollution exposure to dementia. Future studies with improved design, analysis and reporting would fill key evidentiary gaps and provide a solid foundation for recommendations and possible interventions., Competing Interests: The authors declare they have no actual or potential competing financial interests., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The way a construct is measured can differ across cohort study visits, complicating longitudinal comparisons. We demonstrated the use of factor analysis to link differing cognitive test batteries over visits to common metrics representing general cognitive performance, memory, executive functioning, and language., Methods: We used data from three visits (over 26 years) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 14,252). We allowed individual tests to contribute information differentially by race, an important factor to consider in cognitive aging. Using generalized estimating equations, we compared associations of diabetes with cognitive change using general and domain-specific factor scores versus averages of equally weighted standardized test scores., Results: Factor scores provided stronger associations with diabetes at the expense of greater variability around estimates (e.g., for general cognitive performance, -0.064 standard deviation units/year, standard error = 0.015, vs. -0.041 standard deviation units/year, standard error = 0.014), which is consistent with the notion that factor scores more explicitly address error in measuring assessed traits than averages of standardized tests., Conclusions: Factor analysis facilitates use of all available data when measures change over time, and further, it allows objective evaluation and correction for differential item functioning.

Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential.

Importance: Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age., Objective: To evaluate the association between midlife (48-67 years of age) hypertension and the 20-year change in cognitive performance., Design, Setting, and Participants: The 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., Exposures: Hypertension, 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 Measures: Prespecified 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., Results: During 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 Relevance: Midlife 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.

Background: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution., Methods: We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995-2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant's address., Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups., Conclusions: The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects.

Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.

Background: Higher long-term cumulative lead exposure predicts faster cognitive decline in older men, but evidence of an association in women is lacking., Objective: To determine if there is an association between lead exposure and cognitive decline in women., Methods: This study considers a sample of 584 women from the Nurses' Health Study who live in or near Boston, Massachusetts. We quantified lead exposure using biomarkers of lead exposure assessed in 1993-2004 and evaluated cognitive decline by repeated performance on a telephone battery of cognitive tests primarily assessing learning, memory, executive function, and attention completed in 1995-2008. All cognitive test scores were z-transformed for use in analyses. We used linear mixed models with random effects to quantify the association between each lead biomarker and change in cognition overall and on each individual test., Results: Consideration of individual tests showed greater cognitive decline with increased tibia lead concentrations, a measure of long-term cumulative exposure, for story memory and category fluency. The estimated excess annual decline in overall cognitive test z-score per SD increase in tibia bone lead concentration was suggestive, although the confidence intervals included the null (0.024 standard units, 95% confidence interval: -0.053, 0.004 - an additional decline in function equivalent to being 0.33 years older). We found little support for associations between cognitive decline and patella or blood lead, which provide integrated measures of exposure over shorter timeframes., Conclusions: Long-term cumulative lead exposure may be weakly associated with faster cognitive decline in community-dwelling women, at least in some cognitive domains., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background/aims: Our limited understanding of how polyfluoroalkyl chemicals (PFCs) may impact on human health suggests the potential for a protective impact on brain health. This study was designed to explore the association between PFCs and cognitive ability in older adults., Methods: We assessed the association between four PFCs, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS), and self-reported limitation due to difficulty remembering or periods of confusion using data from participants aged 60-85 years from the 1999-2000 and 2003-2008 National Health and Nutrition Examination Surveys. We also considered whether diabetic status or diabetic medication use modifies this association in light of in vitro evidence that PFCs may act on the same receptors as some diabetic medications., Results: In multivariable adjusted models, point estimates suggest a protective association between PFCs and self-reported cognitive limitation (odds ratio, OR; 95% confidence interval, CI) for a doubling in PFC concentration: PFOS (OR, 0.90; 95% CI, 0.78, 1.03), PFOA (OR, 0.92; 95% CI, 0.78, 1.09), PFNA (OR, 0.91; 95% CI, 0.79, 1.04) and PFHxS (OR, 0.93; 95% CI, 0.82, 1.06). The protective association was concentrated in diabetics, with strong, significant protective associations in nonmedicated diabetics., Conclusions: This cross-sectional study suggests that there may be a protective association between exposure to PFCs and cognition in older adults, particularly diabetics., (Copyright © 2012 S. Karger AG, Basel.)

Background: In stroke patients with insulin resistance (IR), post-stroke cognitive impairment (PSCI) is associated with higher risk of recurrent stroke, but the effect of pioglitazone on that risk has not been explored. The goal of this study was to compare the secondary stroke prevention effect of pioglitazone against placebo in patients with versus without PSCI. Methods: We studied patients enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial with a post-stroke modified Mini-Mental State Examination (3MS) cognitive assessment (mean time of assessment: 79 days post-stroke). We considered a baseline score of ⩽ 88 on the 3MS to indicate global PSCI, and domain-specific summary scores in the lowest quartile to indicate attention, language, memory, orientation, and visuospatial impairments. Results: In n = 3338 patients with IR, the effect of pioglitazone versus placebo on secondary stroke significantly differed by initial post-stroke global (interaction p = 0.0127) and memory impairment status (interaction p = 0.0003). Hazard ratios (HRs) were time-dependent such that, among those with either global or memory impairment, pioglitazone has an increasingly stronger protective effect at later timepoints. There was no statistically significant effect of pioglitazone among those without either global or memory impairment. The effect of pioglitazone versus placebo on myocardial infarction (MI) also significantly differed by global impairment status (interaction p = 0.030). Pioglitazone was protective among those with global impairment (HR = 0.23 [95% CI: 0.08, 0.71]) but not among those without (HR = 0.88 [95% CI: 0.59, 1.31]). Conclusion: These data indicate that pioglitazone treatment may be more effective at reducing risk of recurrent stroke and MI in stroke patients with PSCI. Simple cognitive testing 2–3 months post-stroke may identify patients for whom treatment would be most beneficial. [ABSTRACT FROM AUTHOR]

Background: Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. Objective: Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias in an autopsy study. Methods: Coronary arteries were collected, and the largest luminal stenosis was measured. Sociodemographic, clinical, and cognitive information were reported by a reliable next-of-kin. The association was tested using logistic and linear regressions adjusted for sociodemographic and clinical variables. We restricted the sample to individuals that were born in 1935 or earlier and stratified the analysis by cause of death to investigate the role of selection bias. Results: In 253 participants (mean age = 78.0±8.5 years old, 48% male), stenosis was not associated with cognitive impairment (OR = 0.85, 95% CI = 0.69; 1.06, p = 0.15). In individuals who were born before 1936 in the absence of cardiovascular disease as the cause of death, greater stenosis was associated with cognitive impairment (OR = 4.02, 95% CI = 1.39; 11.6, p = 0.01). On the other hand, this association was not present among those born in 1935 or earlier who died of cardiovascular diseases (OR = 0.83, 95% CI = 0.60; 1.16, p = 0.28). Conclusion: We found that higher coronary stenosis was associated with cognitive impairment only in individuals born in 1935 or earlier and who had not died from cardiovascular diseases. Selection bias may be an important issue when investigating risk factors for chronic degenerative diseases in older individuals using autopsy samples. [ABSTRACT FROM AUTHOR]

Introduction As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear. Materials and Methods We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC. Results Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): −0.042 (−0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer's disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness. Conclusions Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults. [ABSTRACT FROM AUTHOR]

Dietary copper intake may be associated with cognitive decline and dementia. We used data from 10,269 participants of the Atherosclerosis Risks in Communities Study to study the associations of dietary copper intake with 20-year cognitive decline and incident dementia. Dietary copper intake from food and supplements was quantified using food frequency questionnaires. Cognition was assessed using 3 cognitive tests at study visits; dementia was ascertained at study visits and via surveillance. Multiple imputation by chained equations was applied to account for the missing information of cognitive function during follow-up. Survival analysis with parametric models and mixed-effect models were used to estimate the associations for incident dementia and cognitive decline, respectively. During 20 years of follow-up (1996–1998 to 2016–2017), 1,862 incident cases of dementia occurred. Higher intake of dietary copper from food was associated with higher risk of incident dementia among those with high intake of saturated fat (hazard ratio = 1.49, 95% confidence interval: 1.04, 1.95). Higher intake of dietary copper from food was associated with greater decline in language overall (beta = −0.12, 95% confidence interval: −0.23, −0.02). Therefore, a diet high in copper, particularly when combined with a diet high in saturated fat, may increase the risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. Methods: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14–180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. Results: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04–2.09) and death (hazard ratio, 1.87; 95% CI: 1.25–2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06–2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14–2.67) were associated with an increased risk of death. Discussion/Conclusion: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death. [ABSTRACT FROM AUTHOR]

Late-life measures of white matter (WM) microstructural integrity may predict cognitive status, cognitive decline, and incident mild cognitive impairment (MCI) or dementia. We considered participants of the Atherosclerosis Risk in Communities study who underwent cognitive assessment and neuroimaging in 2011–2013 and were followed through 2016–2017 (n = 1775 for analyses of prevalent MCI and dementia, baseline cognitive performance, and longitudinal cognitive change and n = 889 for analyses of incident MCI, dementia, or death). Cross-sectionally, both overall WM fractional anisotropy and overall WM mean diffusivity were strongly associated with baseline cognitive performance and risk of prevalent MCI or dementia. Longitudinally, greater overall WM mean diffusivity was associated with accelerated cognitive decline, as well as incident MCI, incident dementia, and mortality, but WM fractional anisotropy was not robustly associated with cognitive change or incident cognitive impairment. Both cross-sectional and longitudinal associations were attenuated after additionally adjusting for likely downstream pathologic changes. Increased WM mean diffusivity may provide an early indication of dementia pathogenesis. • White matter microstructural integrity is associated with cognition. • Cross-sectional and longitudinal associations differ. • White matter mean diffusivity predicts cognitive decline and incident dementia. • Associations appear partially mediated by other brain-based changes. • Poor white matter microstructural integrity may signify dementia pathogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increasing evidence links higher particulate matter (PM) air pollution exposure to late-life cognitive impairment. However, few studies have considered associations between direct estimates of long-term past exposures and brain MRI findings indicative of neurodegeneration or cerebrovascular disease. OBJECTIVE: Our objective was to quantify the association between brain MRI findings and PM exposures approximately 5 to 20 y prior to MRI in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: ARIC is based in four U.S. sites: Washington County, Maryland; Minneapolis suburbs, Minnesota; Forsyth County, North Carolina; and Jackson, Mississippi. A subset of ARIC participants underwent 3T brain MRI in 2011-2013 (n = 1,753). We estimated mean exposures to PM with an aerodynamic diameter less than 10 or 2.5 µm (PM10 and PM2.5) in 1990-1998, 1999-2007, and 1990-2007 at the residential addresses of eligible participants with MRI data. We estimated site-specific associations between PM and brain MRI findings and used random-effect, inverse variance-weighted meta-analysis to combine them. RESULTS: In pooled analyses, higher mean PM2.5 and PM10 exposure in all time periods were associated with smaller deep-gray brain volumes, but not other MRI markers. Higher PM2.5 exposures were consistently associated with smaller total and regional brain volumes in Minnesota, but not elsewhere. CONCLUSIONS: Long-term past PM exposure in was not associated with markers of cerebrovascular disease. Higher long-term past PM exposures were associated with smaller deep-gray volumes overall, and higher PM2.5 exposures were associated with smaller brain volumes in the Minnesota site. Further work is needed to understand the sources of heterogeneity across sites. [ABSTRACT FROM AUTHOR]

Background: Traffic-related particles induce oxidative stress and may exert adverse effects on central nervous system function, which could manifest as cognitive impairment. Objective: We assessed the association between black carbon (BC), a marker of traffic-related air pollution, and cognition in older men. Methods: A total of 680 men (mean ± SD, 71 ± 7 years of age) from the U.S. Department of Veterans Affairs Normative Aging Study completed a battery of seven cognitive tests at least once between 1996 and 2007. We assessed long-term exposure to traffic-related air pollution using a validated spatiotemporal land-use regression model for BC. Results: The association between BC and cognition was nonlinear, and we log-transformed BC estimates for all analyses [ln(BC)]. In a multivariable-adjusted model, for each doubling in BC on the natural scale, the odds of having a Mini-Mental State Examination (MMSE) score ≤ 25 was 1.3.times higher [95% confidence interval (CI), 1.1 to 1.6]. In a multivariable-adjusted model for global cognitive function, which combined scores from the remaining six tests, a doubling of BC was associated with a 0.054 SD lower test score (95% CI, --0.103 to --0.006), an effect size similar to that observed with a difference in age of 1.9 years in our data. We found no evidence of heterogeneity by cognitive test. In sensitivity analyses adjusting for past lead exposure, the association with MMSE scores was similar (odds ratio = 1.3; 95% CI, 1.1 to 1.7), but the association with global cognition was somewhat attenuated (--0.038 per doubling in BC; 95% CI, --0.089 to 0.012). Conclusions: Ambient traffic-related air pollution was associated with decreased cognitive function in older men. [ABSTRACT FROM AUTHOR]

Background: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution.Methods: We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995-2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant's address.Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups.Conclusions: The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects. [ABSTRACT FROM AUTHOR]