Food resources and kitchen skills plus aerobic training (FoRKS+) for black adults with hypertension: A pilot trial protocol.

BACKGROUND: Midlife hypertension is associated with cognitive decline and Alzheimer's disease and related dementia (ADRD), suggesting that blood pressure control may be a therapeutic target for dementia prevention. Given excess hypertension in non-Hispanic Black (NHB) adults, blood pressure control may also reduce ADRD disparities. We describe a pilot randomized controlled trial (RCT) to evaluate the feasibility and preliminary efficacy of a multicomponent lifestyle-based intervention versus enhanced usual care on cognition among middle-aged NHB adults. METHODS AND STUDY DESIGN: The Food Resources and Kitchen Skills plus Aerobic Training (FoRKS+) study is a 2-arm, single-blinded trial that compares those receiving the FoRKS+ program (target N = 64) versus those receiving enhanced usual care (target N = 64) in local federally-qualified health centers. Key eligibility criteria include self-identified NHB adults between ages 35-75 with a mean systolic blood pressure ≥ 130 mm/Hg obtained from 24-h ambulatory blood pressure monitoring. The FoRKS+ program includes 5 weeks of hypertension self-management courses, 11 weeks of nutrition courses, and 12 weeks of aerobic training in dietitian and health coach-led virtual groups. We will collect data on primary cognitive outcomes, feasibility, hypothesized intervention mediators and moderators, and demographic and health covariates at baseline, near intervention weeks 16-, and 28 (primary outcome assessment), and week 52 follow-up. We will use mixed-effects modeling to examine intervention effects on cognition. DISCUSSION: This pilot RCT will examine the feasibility and preliminary effects of a multicomponent lifestyle intervention on cognitive function in NHB adults, which may have implications for reducing health disparities in ADRD.

Spatial transcriptomic patterns underlying amyloid-ß and tau pathology are associated with cognitive dysfunction in Alzheimer's disease.

Amyloid-ß (Aß) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aß and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aß (gene-to-Aß associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts. We identify AD susceptibility genes and gene modules in a gene co-expression network with expression profiles specifically related to regional vulnerability to Aß and tau pathologies in AD. In addition, we identify distinct biochemical pathways associated with the gene-to-Aß and the gene-to-tau associations. These findings may explain the discordance between regional Aß and tau pathologies. Finally, we propose an analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations.

Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective: To evaluate the efficacy of a post-intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants: This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention: A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures: The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results: In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, -1.06 to 4.29] for SF-36 PCS; -2.50 [95% CI, -5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance: Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03053245.

Multi-element Exposure and Cognitive Function in Rural Elderly Chinese.

To investigate the relationship between selenium (Se) based multi-element combined exposure and cognitive function in rural elderly individuals, a cross-sectional study was conducted. The study involved 416 older adults aged 60 and above, residing in four different areas of Enshi county, China, with varying soil Se levels. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to measure the concentrations of Se, copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), cadmium (Cd), arsenic (As), and lead (Pb) in whole blood. Nine standard cognitive tests were applied to assess cognitive function. Analysis of the least absolute shrinkage and selection operator regression (LASSO), covariance (ANCOVA), and generalized linear model (GLM) were utilized to investigate the relationship between element exposure and cognitive function. The results of LASSO revealed that Se, Cu, Fe, Zn, Ca, and Pb were independently identified to be associated with cognition. Both ANCOVA and GLM demonstrated that Se and Ca were correlated with cognitive function. The multi-element model showed higher composite Z scores of 0.32 (95% CI: 0.09 to 0.55) for log-transformed Se (P = 0.007), 0.75 (95% CI: 0.01 to 1.49) for log-transformed Cu (P = 0.048), and a lower score of - 0.67 (95% CI: - 1.26 to - 0.08) for log-transformed Ca (P = 0.025). Furthermore, there was evidence that Se could counteract the negative impact of Ca on cognitive function (P for interaction = 0.031). Our findings suggested that higher levels of Se and Cu were associated with better cognitive function in the elderly and Se can counteract the cognitive damage caused by Ca.

Spatial transcriptomic patterns underlying regional vulnerability to amyloid-ß and tau pathologies and their relationships to cognitive dysfunction in Alzheimer's disease.

Amyloid-ß (Aß) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aß and tau pathologies than others, gene expression may play a role. We studied the association between brain-wide gene expression profiles and regional vulnerability to Aß (gene-to-Aß associations) and tau (gene-to-tau associations) pathologies leveraging two large independent cohorts (n = 715) of participants along the AD continuum. We identified several AD susceptibility genes and gene modules in a gene co-expression network with expression profiles related to regional vulnerability to Aß and tau pathologies in AD. In particular, we found that the positive APOE -to-tau association was only seen in the AD cohort, whereas patients with AD and frontotemporal dementia shared similar positive MAPT -to-tau association. Some AD candidate genes showed sex-dependent negative gene-to-Aß and gene-to-tau associations. In addition, we identified distinct biochemical pathways associated with the gene-to-Aß and the gene-to-tau associations. Finally, we proposed a novel analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations. Taken together, our study identified distinct gene expression profiles and biochemical pathways that may explain the discordance between regional Aß and tau pathologies, and filled the gap between gene-to-pathology associations and cognitive dysfunction in individual AD patients that may ultimately help identify novel personalized pathogenetic biomarkers and therapeutic targets. One Sentence Summary: We identified replicable cognition-related associations between regional gene expression profiles and selectively regional vulnerability to amyloid-ß and tau pathologies in AD.

Amyloid and tau pathology are associated with cerebral blood flow in a mixed sample of nondemented older adults with and without vascular risk factors for Alzheimer's disease.

Identification of biomarkers for the early stages of Alzheimer's disease (AD) is an imperative step in developing effective treatments. Cerebral blood flow (CBF) is a potential early biomarker for AD; generally, older adults with AD have decreased CBF compared to normally aging peers. CBF deviates as the disease process and symptoms progress. However, further characterization of the relationships between CBF and AD risk factors and pathologies is still needed. We assessed the relationships between CBF quantified by arterial spin-labeled magnetic resonance imaging, hypertension, APOEε4, and tau and amyloid positron emission tomography in 77 older adults: cognitively normal, subjective cognitive decline, and mild cognitive impairment. Tau and amyloid aggregation were related to altered CBF, and some of these relationships were dependent on hypertension or APOEε4 status. Our findings suggest a complex relationship between risk factors, AD pathologies, and CBF that warrants future studies of CBF as a potential early biomarker for AD.

Design and baseline characteristics of the Cognitive and Aerobic Resilience for the Brain (CARB) study.

BACKGROUND: Treatments that delay progression of cognitive impairment in older adults are of great public health significance. This manuscript outlines the protocol, recruitment, baseline characteristics, and retention for a randomized controlled trial of cognitive and aerobic physical training to improve cognition in individuals with subjective cognitive dysfunction, the "Cognitive and Aerobic Resilience for the Brain" (CARB) study. METHODS: Community-dwelling, older adults with self-reported memory loss were randomly assigned to receive either computer-based cognitive training, aerobic physical training, combined cognitive and physical training, or education control. Treatment was delivered 2- to 3-times per week in 45- to 90-min sessions for 12 weeks by trained facilitators videoconferencing into subject's home. Outcome assessments of were taken at the baseline, immediately following training, and 3-months after training. RESULTS: 191 subjects were randomized into the trial (mean age, 75.5 years; 68% female; 20% non-white; mean education, 15.1 years; 30% with 1+ APOE e4 allele). The sample was generally obese, hypertensive, and many were diabetic, while cognition, self-reported mood, and activities of daily living were in the normal range. There was excellent retention throughout the trial. Interventions were completed at high rates, participants found the treatments acceptable and enjoyable, and outcome assessments were completed at high rates. CONCLUSIONS: This study was designed to determine the feasibility of recruiting, intervening, and documenting response to treatment in a population at risk for progressive cognitive decline. Older adults with self-reported memory loss were enrolled in high numbers and were well engaged with the intervention and outcome assessments.

Nonalcoholic fatty liver disease and cognitive impairment: A prospective cohort study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase). METHODS: In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples. RESULTS: NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age. CONCLUSIONS: A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health.

Effectiveness of a Single Prolonged Aerobic Exercise Session on Executive Function Task Performance in Physically Active Adults (21-70 Years of Age).

We sought to examine the effectiveness of an acute prolonged exercise session on post-exercise executive function in physically active adults and to assess if age or pre-exercise cognitive performance was predictive of the magnitude of change in executive task performance. Self-registered cyclists were recruited prior to participating in a 161-km mass-participation cycling event. Cyclists were excluded if they had not previously participated in a similar endurance event, were young (<18 y), or were cognitively impaired (Mini CogTM < 3 units). Immediately after completing the exercise session, the time taken to complete Trail Making Test Part A and Part B (TMT A + B) was assessed. A faster time to complete the TMT A + B was observed after exercise (+8.5%; p = 0.0003; n = 62; age range = 21-70 y). The magnitude of change in TMT A + B performance (pre vs. post) was influenced by pre-exercise TMT A + B performance (r2 = 0.23, p < 0.0001), not age (r2 =0.002; p = 0.75). Prolonged exercise had a small-to-moderate effect on post-exercise compared to pre-exercise executive function task performance (Cohen's d = 0.38-0.49). These results support the effectiveness of a single prolonged exercise bout to augment executive function in physically active adults, irrespective of age.

Blood Selenium and Serum Glutathione Peroxidase Levels Were Associated with Serum ß-Amyloid in Older Adults.

BACKGROUND: Studies have established the association between blood ß-amyloid (Aß) levels and Alzheimer's disease, but population-based studies concerning the association between selenium (Se) and Aß levels in blood samples are very limited. Therefore, we explored the association in an elderly population with Se status and serum Aß measures. METHODS: A cross-sectional study on 469 elderly individuals from four rural counties with diverse soil Se levels was carried out. Fasting blood Se, serum selenoprotein P (SELENOP), and glutathione peroxidase (GPX), serum Aß42, and Aß40 were measured. Quantile regression models were used to determine the associations of blood Se, serum GPX, and SELENOP with Aß levels. RESULTS: Significant negative associations were observed between blood Se and serum Aß42 and Aß40 levels at all percentiles (P < 0.05). The associations were generally stronger at higher Aß42 and Aß40 percentiles than lower Aß42 and Aß40 percentiles. Blood Se was positively associated with serum Aß42/Aß40 ratio at 25th, 50th, and 75th percentiles. Significant positive associations were observed between serum GPX and Aß42 and Aß40 levels at all percentiles (P < 0.05). The positive associations were generally stronger at higher Aß42 and Aß40 percentiles than at lower percentiles. Serum GPX was negatively associated with Aß42/Aß40 ratio at 25th, 50th, 75th, and 95th percentiles. No associations with serum SELENOP and Aß levels were observed. CONCLUSIONS: Our results suggest that higher Se levels are associated with lower serum Aß42 and Aß40 levels and with higher Aß42/Aß40 ratio, and the results are specific for different selenoproteins.

Higher blood selenium level is associated with lower risk of hyperhomocysteinemia in the elderly.

BACKGROUND AND AIMS: Earlier studies have reported inconsistent association between selenium (Se) and homocysteine (Hcy) levels, while no evidence could be found from Chinese population. To fill this gap, we investigated the association between blood Se and hyperhomocysteinemia (HHcy) of rural elderly population in China. METHODS: A cross-sectional study on 1823 participants aged 65 and older from four Chinese rural counties was carried out in this study. Whole blood Se and serum Hcy concentrations were measured in fasting blood samples. Analysis of covariance and restricted cubic spline models were used to examine the association between Se and Hcy levels. Logistic regression models were used to evaluate the risk of prevalent HHcy among four Se quartile groups after adjusting for covariates. RESULTS: For this sample, the mean blood Se concentration was 156.34 (74.65) µg/L and the mean serum Hcy concentration was 17.25 (8.42) µmol/L. A significant non-linear relationship was found between blood Se and serum Hcy, the association was inverse when blood Se was less than 97.404 µg/L and greater than 156.919 µg/L. Participants in the top three blood Se quartile groups had significantly lower risk of prevalent HHcy compared with the lowest quartile group. When defined as Hcy> 10 µmol/L, the odds ratios and 95% confidence interval of HHcy were 0.600 (0.390, 0.924), 0.616 (0.398, 0.951) and 0.479 (0.314, 0.732) for Q2, Q3, and Q4 Se quartile groups compared with the Q1 group, respectively. When defined as Hcy≥ 15 µmol/L, the odds ratios and 95% confidence interval of HHcy were 0.833 (0.633, 1.098) and 0.827 (0.626, 1.092), 0.647 (0.489, 0.857) for Q2, Q3, and Q4 Se quartile groups compared with Q1 group. CONCLUSIONS: Our findings suggest that higher blood Se level could be a protective factor for HHcy in the elderly.

Sensitivity of memory subtests and learning slopes from the ADAS-Cog to distinguish along the continuum of the NIA-AA Research Framework for Alzheimer's Disease.

Despite extensive use of the Alzheimer's Disease (AD) Assessment Scale - Cognitive Subscale (ADAS-Cog) in AD research, exploration of memory subtests or process scores from the measure has been limited. The current study sought to establish validity for the ADAS-Cog Word Recall Immediate and Delayed Memory subtests and learning slope scores by showing that they are sensitive to AD biomarker status. Word Recall subtest and learning slope scores were calculated for 441 participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 90). All participants were categorized using the NIA-AA Research Framework - based on PET-imaging of ß-amyloid (A) and tau (T) deposition - as Normal AD Biomarkers (A-T-), Alzheimer's Pathologic Change (A + T-), or Alzheimer's disease (A + T+). Memory subtest and learning slope performances were compared between biomarker status groups, and with regard to how well they discriminated samples with (A + T+) and without (A-T-) biomarkers. Lower Word Recall memory subtest scores - and scores for a particular learning slope calculation, the Learning Ratio - were observed for the AD (A + T+) group than the other biomarker groups. Memory subtest and Learning Ratio scores further displayed fair to good receiver operator characteristics when differentiating those with and without AD biomarkers. When comparing across learning slopes, the Learning Ratio metric consistently outperformed others. ADAS-Cog memory subtests and the Learning Ratio score are sensitive to AD biomarker status along the continuum of the NIA-AA Research Framework, and the results offer criterion validity for use of these subtests and process scores as unique markers of memory capacity.

Assessing and validating reliable change across ADNI protocols.

OBJECTIVE: Reliable change methods can aid in determining whether changes in cognitive performance over time are meaningful. The current study sought to develop and cross-validate 12-month standardized regression-based (SRB) equations for the neuropsychological measures commonly administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI) longitudinal study. METHOD: Prediction algorithms were developed using baseline score, retest interval, the presence/absence of a 6-month evaluation, age, education, sex, and ethnicity in two different samples (n = 192 each) of robustly cognitively intact community-dwelling older adults from ADNI - matched for demographic and testing factors. The developed formulae for each sample were then applied to one of the samples to determine goodness-of-fit and appropriateness of combining samples for a single set of SRB equations. RESULTS: Minimal differences were seen between Observed 12-month and Predicted 12-month scores on most neuropsychological tests from ADNI, and when compared across samples the resultant Predicted 12-month scores were highly correlated. As a result, samples were combined and SRB prediction equations were successfully developed for each of the measures. CONCLUSIONS: Establishing cross-validation for these SRB prediction equations provides initial support of their use to detect meaningful change in the ADNI sample, and provides the basis for future research with clinical samples to evaluate potential clinical utility. While some caution should be considered for measuring true cognitive change over time - particularly in clinical samples - when using these prediction equations given the relatively lower coefficients of stability observed, use of these SRBs reflects an improvement over current practice in ADNI.

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.

Cognitive dysfunction prevalence and associated factors in older breast cancer survivors.

OBJECTIVES: The purpose of this study was to examine the prevalence and factors associated with objective and subjective cognitive dysfunction in older breast cancer survivors (BCS). MATERIALS AND METHODS: This cross-sectional descriptive study leveraged previously collected data from older BCS (n = 335). Separate linear regression models were used to determine relationships between demographic factors (age, education), medical factors (comorbidities), disease factors (time since diagnosis, cancer stage), cancer-related symptoms (depressive symptoms, anxiety, fatigue, sleep disturbance) and cognitive dysfunction measures, including objective learning, delayed recall, attention, executive function-working memory, verbal fluency and subjective attentional function. RESULTS: Cognitive dysfunction was prevalent with up to 18.6% of older BCS experiencing mild-moderate dysfunction (1.5 standard deviations below mean of non-cancer controls) in at least one cognitive domain. Poor to moderate subjective attentional function was reported by 26% of older BCS. More depressive symptoms were significantly related to poorer cognitive function including learning (p < .01), delayed recall (p < .05), verbal fluency (p < .001), and subjective attentional function (p < .001) but not attention and executive function-working memory. Age, education, anxiety, and fatigue were also negatively associated with cognitive function in some models (p < .05-0.001). CONCLUSION: Cognitive dysfunction is common among older BCS and depressive symptoms, anxiety, and fatigue are related factors. Importantly, depressive symptoms were not only related to self-report, but also to cognitive performance. Healthcare providers should be aware of and assess for related factors and cognitive dysfunction itself in older BCS even years after diagnosis and treatment thorough geriatric assessment. Future longitudinal research is needed to discern these relationships.

Association of cognitive impairment and breast cancer survivorship on quality of life in younger breast cancer survivors.

PURPOSE: Younger breast cancer survivors (BCS) often report cognitive impairment and poor quality of life (QoL), which could be interrelated. The purpose of this study was to examine the association of cognitive impairment and breast cancer status (BCS versus healthy control (HC)), with QoL, which included psychological (depressive symptoms, well-being, perceived stress, and personal growth) and physical well-being (physical functioning and fatigue). METHODS: Four hundred ninety-eight BCS (≤45 years at diagnosis) who were 3 to 8 years post-chemotherapy treatment and 394 HC completed subjective questionnaires and a one-time neuropsychological assessment, including tests of attention, memory, processing speed, and verbal fluency. For each test, cognitive impairment was defined as scoring 1.5 and 2.0 standard deviations below the mean of the HC group. Separate linear regression models for each outcome were ran controlling for known covariates. RESULTS: BCS reported significantly more memory problems than HC (p < 0.0001), with up to 23% having significant impairment. Cognitive performance did not differ significantly between BCS and HCs. BCS vs. HCs had greater depression and fatigue, yet more personal growth. Objective and subjective cognitive impairment were significantly related to greater depressive symptoms and perceived stress and lower well-being and physical functioning; whereas, objective impairment was related to less personal growth and subjective impairment was related to greater fatigue. CONCLUSIONS: Younger BCS report significant cognitive impairment years after treatment which may relate to greater decrements in QoL. IMPLICATIONS TO CANCER SURVIVORS: Assessment and interventions to address cognitive concerns may also influence QoL outcomes in younger BCS.

Relation of Atrial Fibrillation to Cognitive Decline (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study).

The association of atrial fibrillation (AF) with cognitive function remains unclear, especially among racially/geographically diverse populations. This analysis included 25,980 black and white adults, aged 48+, from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, free from cognitive impairment and stroke at baseline. Baseline AF was identified by self-reported medical history or electrocardiogram (ECG). Cognitive testing was conducted yearly with the Six Item Screener (SIS) to define impairment and at 2-year intervals to assess decline on: animal naming and letter fluency, Montreal Cognitive Assessment (MoCA), Word List Learning (WLL) and Delayed Recall tasks (WLD). Multivariable regression models estimated the relationships between AF and baseline impairment and time to cognitive impairment. Models were adjusted sequentially for age, sex, race, geographic region, and education, then cardiovascular risk factors and finally incident stroke. AF was present in 2,168 (8.3%) participants at baseline. AF was associated with poorer baseline performance on measures of: semantic fluency (p<0.01); global cognitive performance (MoCA, p<0.01); and WLD (p<0.01). During a mean follow-up of 8.06 years, steeper declines in list learning were observed among participants with AF (p<0.03) which remained significant after adjusting for cardiovascular risk factors (p<0.04) and incident stroke (p<0.03). Effect modification by race, sex and incident stroke on AF and cognitive decline were also detected. In conclusion, AF was associated with poorer baseline cognitive performance across multiple domains and incident cognitive impairment in this bi-racial cohort. Additional adjustment for cardiovascular risk factors attenuated these relations with the exception of learning.

The relationship of cognitive change over time to the self-reported Ascertain Dementia 8-item Questionnaire in a general population.

OBJECTIVE: The aim of the study was to examine the relationship between longitudinally assessed cognitive functioning and self-reported dementia status using the Ascertain Dementia 8-item questionnaire (AD8) in a national population-based sample. METHODS: The analysis included 14,453 participants from the REasons for Geographic and Racial Differences in Stroke study. A validated cutoff of ≥2 symptoms endorsed on the AD8 (administered 10 years after enrollment) represented positive AD8 status. Incident cognitive impairment was defined as change from intact to impaired status in the Six-Item Screener score, and cognitive decline was defined by trajectories of Letter "F" Fluency from the Montreal Cognitive Assessment, and Animal Fluency, Word List Learning, and Word List Delayed recall, all from the Consortium to Establish a Registry for Alzheimer's Disease battery. Logistic regression models controlled for demographics, health variables, and depressive symptoms. RESULTS: Sensitivity and specificity of the AD8 to detect incident cognitive impairment were 45.2% and 78.4%, respectively. Incident cognitive impairment and a one-word decline in WLL increased the odds of self-reported positive AD8 by 96% (95% CI: 1.68-2.28) and 27% (95% CI: 1.17-1.37), respectively. There was a strong association between high depression risk and self-reported positive AD8 in sensitivity analyses. CONCLUSIONS: Incident cognitive impairment and high depression risk were the strongest predictors of self-reported positive AD8 in this population-based sample. Our results inform the utility of the AD8 as a self-report measure in a large, national sample that avoids selection biases inherent in clinic-based studies. The AD8 is screening measure and should not be used to diagnose dementia clinically.

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.

Higher blood cadmium level is associated with greater cognitive decline in rural Chinese adults aged 65 or older.

Cadmium (Cd) exposure has been reported to have neurotoxic effects in animal studies and associated with increased Alzheimer's Disease mortality and lower cognitive function in cross-sectional and case-control studies. However, no results from longitudinal studies on Cd and cognitive decline are available. In this prospective cohort study, we recruited 1867 participants aged 65 years or older from rural areas in China, blood Cd and cognitive function were measured at baseline (2010-2012), and 1554 participants completed cognitive function tests during a 3-year follow-up (2013-2015). Cognitive function was evaluated using nine standardized cognitive tests: The Community Screening Instrument for Dementia, the CERAD Word List Learning, Word list recall, IU Story Recall, Animal Fluency Test, Boston Naming Test, Stick Design, Delayed Stick Design and the IU Token Test. Analysis of covariance models and logistic regression models were used to determine the association between Cd and standardized cognitive decline adjusting for covariates. The median blood Cd concentration of this study population was 2.12 µg/L, and the interquartile range was 1.42-4.64 µg/L. Significant association of higher Cd levels with lower cognitive scores were observed in five individual cognitive tests (Delayed Stick Design Test, Boston Naming Test, CERAD Word List Learning Test, Word List Recall Test and IU Story Recall Test) and the composite cognitive score adjusting for multi-covariates at baseline. Higher Cd levels were significantly associated with greater 3-year cognitive decline in Delayed Stick Design Test, Boston Naming Test, IU Token Test, Word List Recall Test and Composite cognitive score. For these cognitive tests, participants in the top two Cd quartile groups had significantly greater decline than those in the lowest Cd quartile group, while the two lowest Cd quartile groups were not significantly different. Our findings suggest that higher Cd exposure is associated with greater cognitive decline in older Chinese adults.