Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

PURPOSE: There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort. METHODS: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003-2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression. RESULTS: Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10 years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models. CONCLUSION: Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment.

Hippocampal-subfield microstructures and their relation to plasma biomarkers in Alzheimer's disease.

Hippocampal subfields exhibit differential vulnerabilities to Alzheimer's disease-associated pathology including abnormal accumulation of amyloid-ß deposition and neurofibrillary tangles. These pathological processes extensively impact on the structural and functional interconnectivities of the subfields and may explain the association between hippocampal dysfunction and cognitive deficits. In this study, we investigated the degree of alterations in the microstructure of hippocampal subfields across the clinical continuum of Alzheimer's disease. We applied a grey matter-specific multi-compartment diffusion model (Cortical-Neurite orientation dispersion and density imaging) to understand the differential effects of Alzheimer's disease pathology on the hippocampal subfield microstructure. A total of 119 participants were included in this cross-sectional study. Participants were stratified into three categories, cognitively normal (n = 47), mild cognitive impairment (n = 52), and Alzheimer's disease (n = 19). Diffusion MRI, plasma biomarkers and neuropsychological test scores were used to determine the association between the microstructural integrity and Alzheimer's disease-associated molecular indicators and cognition. For Alzheimer's disease-related plasma biomarkers, we studied amyloid-ß, total tau and neurofilament light; for Alzheimer's disease-related neuropsychological tests, we included the Trail Making Test, Rey Auditory Verbal Learning Test, Digit Span and Montreal Cognitive Assessment. Comparisons between cognitively normal subjects and those with mild cognitive impairment showed significant microstructural alterations in the hippocampal cornu ammonis (CA) 4 and dentate gyrus region, whereas CA 1-3 was the most sensitive region for the later stages in the Alzheimer's disease clinical continuum. Among imaging metrics for microstructures, the volume fraction of isotropic diffusion for interstitial free water demonstrated the largest effect size in between-group comparisons. Regarding the plasma biomarkers, neurofilament light appeared to be the most sensitive biomarker for associations with microstructural imaging findings in CA4-dentate gyrus. CA 1-3 was the subfield which had stronger correlations between cognitive performance and microstructural metrics. Particularly, poor performance on the Rey Auditory Verbal Learning Test and Montreal Cognitive Assessment was associated with decreased intracellular volume fraction. Overall, our findings support the value of tissue-specific microstructural imaging for providing pathologically relevant information manifesting in the plasma biomarkers and neuropsychological outcomes across various stages of Alzheimer's disease.

Post-Processing Automatic Transcriptions with Machine Learning for Verbal Fluency Scoring.

Objective: To compare verbal fluency scores derived from manual transcriptions to those obtained using automatic speech recognition enhanced with machine learning classifiers. Methods: Using Amazon Web Services, we automatically transcribed verbal fluency recordings from 1400 individuals who performed both animal and letter F verbal fluency tasks. We manually adjusted timings and contents of the automatic transcriptions to obtain "gold standard" transcriptions. To make automatic scoring possible, we trained machine learning classifiers to discern between valid and invalid utterances. We then calculated and compared verbal fluency scores from the manual and automatic transcriptions. Results: For both animal and letter fluency tasks, we achieved good separation of valid versus invalid utterances. Verbal fluency scores calculated based on automatic transcriptions showed high correlation with those calculated after manual correction. Conclusion: Many techniques for scoring verbal fluency word lists require accurate transcriptions with word timings. We show that machine learning methods can be applied to improve off-the-shelf ASR for this purpose. These automatically derived scores may be satisfactory for some applications. Low correlations among some of the scores indicate the need for improvement in automatic speech recognition before a fully automatic approach can be reliably implemented.

Tau-related white-matter alterations along spatially selective pathways.

Progressive accumulation of tau neurofibrillary tangles in the brain is a defining pathologic feature of Alzheimer's disease (AD). Tau pathology exhibits a predictable spatiotemporal spreading pattern, but the underlying mechanisms of this spread are poorly understood. Although AD is conventionally considered a disease of the gray matter, it is also associated with pronounced and progressive deterioration of the white matter (WM). A link between abnormal tau and WM degeneration is suggested by findings from both animal and postmortem studies, but few studies demonstrated their interplay in vivo. Recent advances in diffusion magnetic resonance imaging and the availability of tau positron emission tomography (PET) have made it possible to evaluate the association of tau and WM degeneration (tau-WM) in vivo. In this study, we explored the spatial pattern of tau-WM associations across the whole brain to evaluate the hypothesis that tau deposition is associated with WM microstructural alterations not only in isolated tracts, but in continuous structural connections in a stereotypic pattern. Sixty-two participants, including 22 cognitively normal subjects, 22 individuals with subjective cognitive decline, and 18 with mild cognitive impairment were included in the study. WM characteristics were inferred by classic diffusion tensor imaging (DTI) and a complementary diffusion compartment model - neurite orientation dispersion and density imaging (NODDI) that provides a proxy for axonal density. A data-driven iterative searching (DDIS) approach, coupled with whole-brain graph theory analyses, was developed to continuously track tau-WM association patterns. Without applying prior knowledge of the tau spread, we observed a distinct spatial pattern that resembled the typical propagation of tau pathology in AD. Such association pattern was not observed between diffusion and amyloid-ß PET signal. Tau-related WM degeneration is characterized by an increase in the mean diffusivity (with a dominant change in the radial direction) and a decrease in the intra-axonal volume fraction. These findings suggest that cortical tau deposition (as measured in tau PET) is associated with a lower axonal packing density and greater diffusion freedom. In conclusion, our in vivo findings using a data-driven method on cross-sectional data underline the important role of WM alterations in the AD pathological cascade with an association pattern similar to the postmortem Braak staging of AD. Future studies will focus on longitudinal analyses to provide in vivo evidence of tau pathology spreads along neuroanatomically connected brain areas.

Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study.

PURPOSE: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. METHODS: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. CONCLUSIONS: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.

The Prevalence of Cognitive Impairment Among Adults With Incident Heart Failure: The "Reasons for Geographic and Racial Differences in Stroke" (REGARDS) Study.

BACKGROUND: Cognitive impairment (CI) is estimated to be present in 25%-80% of heart failure (HF) patients, but its prevalence at diagnosis is unclear. To improve our understanding of cognition in HF, we determined the prevalence of CI among adults with incident HF in the REGARDS study. METHODS AND RESULTS: REGARDS is a longitudinal cohort study of adults ≥45 years of age recruited in the years 2003-2007. Incident HF was expert adjudicated. Cognitive function was assessed with the Six-Item Screener. The prevalence of CI among those with incident HF was compared with the prevalence of CI among an age-, sex-, and race-matched cohort without HF. The 436 participants with incident HF had a mean age of 70.3 years (SD 8.9), 47% were female, and 39% were black. Old age, black race, female sex, less education, and anticoagulation use were associated with CI. The prevalence of CI among participants with incident HF (14.9% [95% CI 11.7%-18.6%]) was similar to the non-HF matched cohort (13.4% [11.6%-15.4%]; P < .43). CONCLUSIONS: A total of 14.9% of the adults with incident HF had CI, suggesting that the majority of cognitive decline occurs after HF diagnosis. Increased awareness of CI among newly diagnosed patients and ways to mitigate it in the context of HF management are warranted.

Verbal fluency in a national sample: Telephone administration methods.

OBJECTIVES: Describe novel methods for ascertaining verbal fluency in a large national sample of adults, examine demographic factors influencing performance, and compare scores to studies using in-person assessment. METHODS/DESIGN: Participants were from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal study of stroke in adults aged 45 years and older. Letter and semantic fluency were gathered, using Letter "F" and Animal Naming, via a telephone-based assessment with computer-assisted scoring of digital recordings. RESULTS: Initial letter and semantic fluency scores were obtained on 18 505 and 18 072 participants, respectively. For both fluency tests, scores were normally distributed. Younger age and more years of education were associated with better performances (p < 0.0001). The mean and standard deviation for matched subgroups, based on age, gender, and education, were quite comparable with scores reported out of samples using an in-person administration format. Telephone-based assessment also allowed for a level of quality control not available via in-person measurement. CONCLUSIONS: Telephone-based assessment of verbal fluency and computer-assisted scoring programs designed for this study facilitated large-scale data acquisition, storage, and scoring of protocols. The resulting scores have similar characteristics to those obtained by traditional methods. These findings extend validation of cognitive assessment methods, using survey research staff and computer-assisted technology for test administration.

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. METHODS: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. RESULTS: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. CONCLUSIONS: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

Risk Factors for Poststroke Cognitive Decline: The REGARDS Study (Reasons for Geographic and Racial Differences in Stroke).

BACKGROUND AND PURPOSE: Poststroke cognitive decline causes disability. Risk factors for poststroke cognitive decline independent of survivors' prestroke cognitive trajectories are uncertain. METHODS: Among 22 875 participants aged ≥45 years without baseline cognitive impairment from the REGARDS cohort (Reasons for Geographic and Racial Differences in Stroke), enrolled from 2003 to 2007 and followed through September 2015, we measured the effect of incident stroke (n=694) on changes in cognitive functions and cognitive impairment (Six-Item Screener score <5) and tested whether patient factors modified the effect. Median follow-up was 8.2 years. RESULTS: Incident stroke was associated with acute declines in global cognition, new learning, verbal memory, and executive function. Acute declines in global cognition after stroke were greater in survivors who were black (P=0.04), men (P=0.04), and had cardioembolic (P=0.001) or large artery stroke (P=0.001). Acute declines in executive function after stroke were greater in survivors who had

Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study.

BACKGROUND: African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN: Prospective cohort. PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES: Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications.

Self-perceived Difficulties in Everyday Function Precede Cognitive Decline among Older Adults in the ACTIVE Study.

OBJECTIVES: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. METHODS: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. RESULTS: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. CONCLUSIONS: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104-112).

Changes of glucose levels precede dementia in African-Americans with diabetes but not in Caucasians.

INTRODUCTION: Changes in glucose levels may represent a powerful metabolic indicator of dementia in African-Americans with diabetes. It is unclear whether these changes also occur in Caucasians. METHODS: A secondary data analysis using electronic medical records from 5228 African-Americans and Caucasians aged ≥65 years was carried out. Mixed effects models with repeated serum glucose measurements were used to compare changes in glucose levels between African-Americans and Caucasian patients with and without incident dementia. RESULTS: African-Americans and Caucasians with diabetes had significantly different changes in glucose levels by dementia status (P < .0001). African-Americans experienced a significant decline in glucose levels before the dementia diagnosis (estimated glucose decline 1.3421 mg/dL per year, P < .0001) than those who did not develop dementia. Caucasians with and without dementia showed stable glucose levels over time (P = .3071). DISCUSSION: Significant changes in glucose levels precede dementia in African-American patients with diabetes but not in Caucasians.

Glucose level decline precedes dementia in elderly African Americans with diabetes.

INTRODUCTION: High blood glucose levels may be responsible for the increased risk for dementia in diabetic patients. METHODS: A secondary data analysis merging electronic medical records (EMRs) with data collected from the Indianapolis-Ibadan Dementia project (IIDP). Of the enrolled 4105 African Americans, 3778 were identified in the EMR. Study endpoints were dementia, mild cognitive impairment (MCI), or normal cognition. Repeated serum glucose measurements were used as the outcome variables. RESULTS: Diabetic participants who developed incident dementia had a significant decrease in serum glucose levels in the years preceding the diagnosis compared to the participants with normal cognition (P = .0002). They also had significantly higher glucose levels up to 9 years before the dementia diagnosis (P = .0367). DISCUSSION: High glucose levels followed by a decline occurring years before diagnosis in African American participants with diabetes may represent a powerful presymptomatic metabolic indicator of dementia.

Does targeted cognitive training reduce educational disparities in cognitive function among cognitively normal older adults?

OBJECTIVE: The aim of this study was to investigate educational differences in treatment responses to memory, reasoning, and speed of processing cognitive training relative to no-contact control. METHODS: Secondary analyses of the Advanced Cognitive Training for Independent and Vital Elderly trial were conducted. Two thousand eight hundred older adults were randomized to memory, reasoning, or speed of processing training or no-contact control. A repeated-measures mixed-effects model was used to investigate immediate post-training and 1-year outcomes with sensitivity analyses out to 10 years. Outcomes were as follows: (1) memory composite of Hopkins Verbal Learning Test, Rey Auditory Verbal Learning Test, and Rivermead Behavioral Memory Test; (2) reasoning composite of letter series, letter sets, and word series; and (3) speed of processing measured using three trials of useful field of view and the digit symbol substitution test. RESULTS: The effects of reasoning and memory training did not differ by educational attainment. The effect of speed of processing training did. Those with fewer than 12 years of education experienced a 50% greater effect on the useful field of view test compared with those with 16 or more years of education. The training advantage for those with fewer than 12 years of education was maintained to 3 years post-training. CONCLUSION: Older adults with less than a secondary education are at elevated risk of dementia, including Alzheimer's disease. The analyses here indicate that speed of processing training is effective in older adults with low educational attainment.

Nail Selenium Level and Diabetes in Older People in Rural China.

This cross-sectional study aimed to examine the association between selenium levels and diabetes in an older population with life-long natural exposure to selenium in rural China. A total of 1856 subjects aged 65 years or older from four Chinese rural counties with different environmental selenium levels were evaluated. Analysis of covariance models and logistic regression models were used to examine the relationship between nail selenium levels and serum glucose, serum insulin, insulin resistance [using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)], and the risk of diabetes. The mean nail selenium level was 0.461 µg/g and the prevalence rate of diabetes was 8.3% in this population. The mean nail selenium level was significantly higher in the group with diabetes than in the group without diabetes (P<0.0001). The adjusted odds ratios for diabetes were 2.65 (95% CI: 1.48 to 4.73), 2.47 (95% CI: 1.37 to 4.45), and 3.30 (95% CI: 1.85 to 5.88) from the second selenium quartile to the fourth quartile, respectively, compared with the first quartile group. The mean serum glucose and HOMA-IR in the higher selenium quartile groups were significantly higher than those of the lowest quartile group. However, no significant differences in insulin were observed among the four quartile groups. A long-term, higher level of exposure to selenium may be associated with a higher risk of diabetes. Future studies are needed to elucidate the association between selenium and insulin resistance.

Dementia incidence declined in African-Americans but not in Yoruba.

INTRODUCTION: To compare dementia incidence of African-American and Yoruba cohorts aged ≥70 years enrolled in 1992 and 2001. METHODS: African-Americans residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years until 2009. The cohorts consist of 1440 African-Americans, 1774 Yoruba in 1992 and 1835 African-Americans and 1895 Yoruba in the 2001 cohorts aged ≥70 years. RESULTS: In African-Americans, dementia and Alzheimer's disease (AD) incidence rates were significantly lower in 2001 than 1992 for all age groups except the oldest group. The overall standardized annual dementia incidence rates were 3.6% (95% confidence interval [CI], 3.2%-4.1%) in the 1992 cohort and 1.4% (95% CI, 1.2%-1.7%) in the 2001 cohort. There was no significant difference in dementia or AD incidence between the Yoruba cohorts. DISCUSSION: Future research is needed to explore the reasons for the differential changes in incidence rates in these two populations.

Adherence to a Mediterranean diet and prediction of incident stroke.

BACKGROUND AND PURPOSE: There are limited data on the potential association of adherence to Mediterranean diet (MeD) with incident stroke. We sought to assess the longitudinal association between greater adherence to MeD and risk of incident stroke. METHODS: We prospectively evaluated a population-based cohort of 30 239 individuals enrolled in REasons for Geographic and Racial Differences in Stroke (REGARDS) study, after excluding participants with stroke history, missing demographic data or food frequency questionnaires, and unavailable follow-up information. Adherence to MeD was categorized using MeD score. Incident stroke was adjudicated by expert panel review of medical records during a mean follow-up period of 6.5 years. RESULTS: Incident stroke was identified in 565 participants (2.8%; 497 and 68 cases of ischemic stroke [IS] and hemorrhagic stroke, respectively) of 20 197 individuals fulfilling the inclusion criteria. High adherence to MeD (MeD score, 5-9) was associated with lower risk of incident IS in unadjusted analyses (hazard ratio, 0.83; 95% confidence interval, 0.70-1.00; P=0.046). The former association retained its significance (hazard ratio, 0.79; 95% confidence interval, 0.65-0.96; P=0.016) after adjustment for demographics, vascular risk factors, blood pressure levels, and antihypertensive medications. When MeD was evaluated as a continuous variable, a 1-point increase in MeD score was independently associated with a 5% reduction in the risk of incident IS (95% confidence interval, 0-11%). We documented no association of adherence to MeD with incident hemorrhagic stroke. There was no interaction of race (P=0.37) on the association of adherence to MeD with incident IS. CONCLUSIONS: High adherence to MeD seems to be associated with a lower risk of incident IS independent of potential confounders. Adherence to MeD is not related to the risk of incident hemorrhagic stroke.

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans.

OBJECTIVE: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. DESIGN: Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. SETTING: Indianapolis, Indiana. PARTICIPANTS: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. MAIN OUTCOME MEASURES: Incident dementia and incident AD. RESULTS: After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. CONCLUSIONS: Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.

Trajectory of Cognitive Decline After Incident Stroke.

IMPORTANCE: Cognitive decline is a major cause of disability in stroke survivors. The magnitude of survivors' cognitive changes after stroke is uncertain. OBJECTIVE: To measure changes in cognitive function among survivors of incident stroke, controlling for their prestroke cognitive trajectories. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 23,572 participants 45 years or older without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, residing in the continental United States, enrolled 2003-2007 and followed up through March 31, 2013. Over a median follow-up of 6.1 years (interquartile range, 5.0-7.1 years), 515 participants survived expert-adjudicated incident stroke and 23,057 remained stroke free. EXPOSURE: Time-dependent incident stroke. MAIN OUTCOMES AND MEASURES: The primary outcome was change in global cognition (Six-Item Screener [SIS], range, 0-6). Secondary outcomes were change in new learning (Consortium to Establish a Registry for Alzheimer Disease Word-List Learning; range, 0-30), verbal memory (Word-List Delayed Recall; range, 0-10), and executive function (Animal Fluency Test; range, ≥0), and cognitive impairment (SIS score <5 [impaired] vs ≥5 [unimpaired]). For all tests, higher scores indicate better performance. RESULTS: Stroke was associated with acute decline in global cognition (0.10 points [95% CI, 0.04 to 0.17]), new learning (1.80 points [95% CI, 0.73 to 2.86]), and verbal memory (0.60 points [95% CI, 0.13 to 1.07]). Participants with stroke, compared with those without stroke, demonstrated faster declines in global cognition (0.06 points per year faster [95% CI, 0.03 to 0.08]) and executive function (0.63 points per year faster [95% CI, 0.12 to 1.15]), but not in new learning and verbal memory, compared with prestroke slopes. Among survivors, the difference in risk of cognitive impairment acutely after stroke, compared with immediately before stroke, was not statistically significant (odds ratio, 1.32 [95% CI, 0.95 to 1.83]; P = .10); however, there was a significantly faster poststroke rate of incident cognitive impairment compared with the prestroke rate (odds ratio, 1.23 per year [95% CI, 1.10 to 1.38]; P < .001). For a 70-year-old black woman with average values for all covariates at baseline, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference of 4.0% (95% CI, -1.2% to 9.2%) at year 3 and 12.4% (95% CI, 7.7% to 17.1%) at year 6. CONCLUSIONS AND RELEVANCE: Incident stroke was associated with an acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years.

Comparison of younger and older breast cancer survivors and age-matched controls on specific and overall quality of life domains.

BACKGROUND: Younger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). This study sought to determine the effect of breast cancer and age at diagnosis on quality of life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 years or before, 2) OS diagnosed between 55 and 70, and 3) for the YSs, age-matched controls (AC) of women not diagnosed with breast cancer. METHODS: Using a large Eastern Cooperative Oncology Group (ECOG) database, 505 YS were recruited who were aged 45 years or younger when diagnosed and 622 OS diagnosed at 55 to 70 years of age. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables. RESULTS: Compared to both AC and to OS, YS reported more depressive symptoms (P = .005) and fatigue (P < .001), poorer self-reported attention function (P < .001), and poorer sexual function (P < .001) than either comparison group. However, YS also reported a greater sense of personal growth (P < .001) and perceived less social constraint (P < .001) from their partner than AC. CONCLUSIONS: YS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long-term QoL problems than survivors diagnosed at a later age.