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Rationale and Objectives: This study examined the brain effects of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which are incompletely understood. Our objective was to ascertain within-person changes associated with mild coronavirus disease 2019 (COVID-19) in otherwise healthy adults., Materials and Methods: We leveraged existing pre-pandemic baseline neuroimaging and neurocognitive data, and collected follow-up data from uninfected controls and individuals with prior mild COVID-19, during December 2020 and January 2021, when vaccines were not yet available. We compared change during follow-up in patients (n = 5) versus controls (n = 15)., Results: We identified a decrease of intracellular volume fraction (ICVF), decrease of isotropic volume fraction (ISO) and decrease of orientation dispersion index (ODI) in multiple inferior frontal regions of interest in COVID-19 patients; this longitudinal change was significantly different from the control group which demonstrated increases in equivalent measures. This pattern suggests injury with neuronal loss and/or inflammation as underlying mechanisms. Neurocognitive studies identified a pattern of cognitive decline (processing speed, executive function, verbal learning, working memory) in patients, that did not reach significance., Conclusion: Our pilot data suggests that mild COVID-19 may result in brain pathology and impact neurocognitive function in younger adults in a manner parallel to prior findings in older individuals. Though findings may not generalize to other SARS-CoV-2 variants, larger longitudinal studies of mild COVID-19 should be undertaken to understand the potential clinical implications of these findings over the longer term., Competing Interests: The authors declare that they have no known completing financial interest of personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis. Enlarged PVS and infarcts appear to develop in the early 30s, while microbleeds, WMH, amyloid, and tau emerge in the mid to late 30s. Age-residualized WMH were higher in women, in individuals with dementia, and with lower body mass index. Participants with hypertension and APOE-ε4 had higher age-residualized PVS and microbleeds, respectively. Lifespan trajectories demonstrate a dramatic cerebrovascular profile in adults with Down syndrome that appears to evolve developmentally in parallel with AD pathophysiology approximately two decades prior to dementia symptoms., (© 2024. The Author(s).)

Study Objectives: Although sleep affects a range of waking behaviors, the majority of studies have focused on sleep loss with relatively little attention on sustained periods of adequate sleep. The goal of this study was to use an experimental design to examine the effect of both of these sleep patterns on cognitive performance in healthy adults., Methods: This study used a randomized crossover design. Participants who regularly slept 7-9 hours/night completed two 6-week intervention conditions, adequate sleep (maintenance of habitual bed/wake times) and insufficient sleep (reduction in sleep of 1.5 hours relative to adequate sleep), separated by a 2-6weeks (median=43days) washout period. Cognitive functioning was evaluated at baseline and endpoint of each intervention using the NIH Toolbox Cognition Battery. General linear models contrasted scores following each condition to the baseline of the first condition; the baseline of the second condition was included to evaluate practice effects., Results: Sixty-five participants (age 35.9 ± 4.9years, 89% women, 52% non-White race/ethnicity) completed study procedures. There was improvement in performance on the List Sorting Working Memory task after the adequate sleep condition that exceeded practice effects. Cognitive performance after insufficient sleep did not reach the level expected with practice and did not differ from baseline. A similar pattern was found on the Flanker Inhibitory Control and Attention task., Conclusions: These findings contribute to our understanding of the complex interplay between sleep and cognition and demonstrate that consistent, stable sleep of at least 7 hours/night improves working memory and response inhibition in healthy adults., Clinical Trial Registration: The manuscript reports on data from two clinical trials: Impact of Sleep Restriction on Performance in Adults (URL: https://clinicaltrials.gov/ct2/show/NCT02960776, ID Number: NCT02960776) and Impact of Sleep Restriction in Women (URL: https://clinicaltrials.gov/ct2/show/NCT02835261, ID Number: NCT02835261)., Competing Interests: Declaration of conflict of interest The authors have no conflicts of interest., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial., Methods: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status., Results: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status., Conclusion: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention., (© 2024. The Author(s).)

Introduction: This study describes changes in the mental health, financial security, and physical activity levels of women in North Carolina during the COVID-19 pandemic., Methods: Data were collected from women aged 20-40 years receiving primary care at 2 health centers in North Carolina during 2020-2022. Surveys (N=127) evaluated changes in mental health, financial security, and physical activity during the COVID-19 pandemic. These outcomes were analyzed both descriptively and for association with sociodemographic factors using logistic regression. A subset of participants ( n =46) participated in semistructured interviews. Interview transcripts were reviewed and evaluated for recurring themes by primary and secondary coders using a rapid-coding technique. Analysis was conducted in 2022., Results: Women surveyed were 28.4% non-Hispanic White, 38.6% non-Hispanic Black, and 33.1% Hispanic/Latina. Compared with reports before the pandemic, participants reported increased frustration or boredom (69.1%), loneliness (51.6%), anxiety (64.3%), depression (52.4%), and changed sleep patterns (68.3%). Increased alcohol and other recreational substance use were associated with race and ethnicity ( p <0.05) after adjustment for other sociodemographic factors. Participants reported difficulty in paying for basic expenses (44.0%). Financial difficulties during COVID-19 were associated with non-Hispanic Black race and ethnicity, less education, and lower prepandemic household income. Data showed pandemic-associated reductions in mild (32.8%), moderate (39.5%), and strenuous (43.3%) exercise, with a correlation between increased depression and reduced mild exercise. Interviews identified themes including reduced activity while working remotely, lack of gym access, and reduced motivation for exercise., Conclusions: This mixed-methods study is one of the first to evaluate the mental health, financial security, and physical activity challenges women aged between 20 and 40 years in the southern U.S. faced during the COVID-19 pandemic., (© 2023 The Authors.)

Study Objectives: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity., Methods: We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ± 1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ± 1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis., Results: We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ± 0.02 ml vs. 0.18 ± 0.02 ml, β = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002)., Conclusions: Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players., Methods: The sample included 276 active amateur soccer players (196 male and 81 female) aged 18-53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under., Results: We found that soccer players who began heading at age 10 or younger performed better on tests of working memory ( p = 0.03) and verbal learning ( p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups., Discussion: The findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety., Competing Interests: RL reports receiving research support from the NIH, FDA as well as the National Headache Foundation and the Marx Foundation, and receives research support from Allergan/Abbvie, Amgen, Eli Lilly and Electrocore, and receives personal fees as a consultant or advisor from Allergan/Abbvie, Amgen, Biohaven Holdings, Dr. Reddy's, GlaxoSmithKline, Grifols, Lundbeck, Merck, Novartis and Teva Pharmaceuticals, he holds stock or options in Biohaven Holdings and CtrlM Health. In addition, he receives royalties for Wolff's Headache 7th and 8th Edition. ML reports receiving research support from the NIH and Dana Foundation. WS was employed by Medcurio Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Charney, Ye, Fleysher, DeMessie, Stewart, Zimmerman, Kim, Lipton and Lipton.)

Objectives: To determine the impact of 12-month heading exposure on short-term learning., Design: A total of 105 active amateur soccer players, 45 women and 60 men, were administered an EMA-based test of working memory, a version of the two-back, once daily for 14 days., Methods: Heading exposure of the participants was assessed using "HeadCount", a validated structured questionnaire at the baseline visits. The short-term rate of learning of each individual is quantified by first fitting a quadratic model to the daily performance on the two-back test over a two-week period, then taking the instantaneous rate of the quadratic function at the 7th test. A linear regression model was used to test the association of heading exposure with rates of learning, including age, sex, years of education and history of concussion as covariates, as well as variables describing soccer play and heading within the two-week period. Sensitivity analyses were performed using different methods for quantifying the learning effects and different transformations on 12-month heading exposure., Results: Greater 12-month heading was associated with lower rates of learning among women (p = 0.008) but not among men (p = 0.74)., Conclusions: We have identified evidence for an adverse, albeit subclinical, effect of soccer heading on brain function among young adult players, which selectively affects women in our sample., (Copyright © 2022 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objective Progressive word-finding difficulty is a primary cognitive complaint among healthy older adults and a symptom of pathological aging. Classic measures of visual confrontation naming, however, show ceiling effects among healthy older adults. To address the need for a naming test that is sensitive to subtle, age-related word-finding decline, we developed the Rapid Naming Test (RNT), a computerized, one-minute, speeded visual naming test. Method Functionally intact older ( n  = 145) and younger ( n  = 69) adults completed the RNT. Subsets of older adults also completed neuropsychological tests, a self-report scale of functional decline, amyloid-β PET imaging, and repeat RNT administration to determine test-retest reliability. Results RNT scores were normally distributed and exhibited good test-retest reliability. Younger adults performed better than older adults. Within older adults, lower scores were associated with older age. Higher scores correlated with measures of language, processing speed, and episodic learning and memory. Scores were not correlated with visuospatial or working memory tests. Worse performance was related to subjective language decline, even after controlling for a classic naming test and speed. The RNT was also negatively associated with amyloid-β burden. Conclusions The RNT appears to be a reliable test that is sensitive to subtle, age-related word-finding decline. Convergent and divergent validity are supported by its specific associations with measures relying on visual naming processes. Ecological validity is supported by its relationship with subjective real-world language difficulties. Lastly, worse performance was related to amyloid-β deposition, an Alzheimer's disease biomarker. This study represents a key step toward validating a novel, sensitive naming test in typically aging adults.

Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimer's disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimer's disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination., (© 2022 the Alzheimer's Association.)

Study Objectives: Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized that OSA in children reorganizes and alters cortical structure, which can cause changes in cortical thickness correlation between brain regions across subjects., Methods: We constructed cortical structure networks based on cortical thickness measurements from 41 controls (age 15.54 ± 1.66 years, male 19) and 50 children with OSA (age 15.32 ± 1.65 years, male 29). The global (clustering coefficient [CC], path length, and small-worldness) and regional (nodal betweenness centrality, NBC) network properties and hub region distributions were examined between groups., Results: We found increased CCs in OSA compared to controls across a wide range of network densities (p-value < .05) and lower NBC area under the curve in left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral gyri (p-value < .05). In addition, while most of the hub regions were the same between groups, the OSA group had fewer hub regions and a different hub distribution compared to controls., Conclusions: Our findings suggest that children with OSA exhibit altered global and regional network characteristics compared to healthy controls. Our approach to the investigation of cortical structure in children with OSA could prove useful in understanding the etiology of OSA-related brain functional disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We determined the extent to which obstructive sleep apnea (OSA) is associated with increased cerebrovascular disease and amyloid burden, and the relation of the two processes across clinical Alzheimer's disease (AD) diagnostic groups in adults with Down syndrome (DS). Adults with DS from the Biomarkers of Alzheimer's Disease in Down Syndrome (ADDS) study were included given available research MRI ( n = 116; 50 ± 8 years; 42% women) and amyloid PET scans ( n = 71; 50 ± 7 years; 39% women) at the time of analysis. Participants were characterized as cognitively stable (CS; 64%), with mild cognitive impairment-DS (MCI-DS; 23%), with possible AD dementia (5%), or with definite AD dementia (8%). OSA was determined via medical records and interviews. Models tested the effect of OSA on MRI-derived cerebrovascular biomarkers and PET-derived amyloid burden, and the moderating effect of OSA and AD diagnosis on biomarkers. OSA was reported in 39% of participants, which did not differ by clinical AD diagnostic group. OSA was not associated with cerebrovascular biomarkers but was associated with greater cortical amyloid burden. White matter hyperintensity (WMH) volume (primarily in the parietal lobe), enlarged perivascular spaces, and cortical and striatal amyloid burden were greater across clinical AD diagnostic groups (CS

Background: Coronary CT angiography (CCTA) and contrast-enhanced thoracic CT (CECT) are distinctly different diagnostic procedures that involve intravenous contrast-enhanced CT of the chest. The technical component of these procedures is reimbursed at the same rate by the Centers for Medicare and Medicaid Services (CMS). This study tests the hypothesis that the direct costs of performing these exams are significantly different., Methods: Direct costs for both procedures were measured using a time-driven activity-based costing (TDABC) model. The exams were segmented into four phases: preparation, scanning, post-scan monitoring, and image processing. Room occupancy and direct labor times were collected for scans of 54 patients (28 CCTA and 26 CECT studies), in seven medical facilities within the USA and used to impute labor and equipment cost. Contrast material costs were measured directly. Cost differences between the exams were analyzed for significance and variability., Results: Mean CCTA duration was 3.2 times longer than CECT (121 and 37 ​min, respectively. p ​< ​0.01). Mean CCTA direct costs were 3.4 times those of CECT ($189.52 and $55.28, respectively, p ​< ​0.01). Both labor and capital equipment costs for CCTA were significantly more expensive (6.5 and 1.8-fold greater, respectively, p ​< ​0.001). Segmented by procedural phase, CCTA was both longer and more expensive for each (p ​< ​0.01). Mean direct costs for CCTA exceeded the standard CMS technical reimbursement of $182.25 without accounting for indirect or overhead costs., Conclusion: The direct cost of performing CCTA is significantly higher than CECT, and thus reimbursement schedules that treat these procedures similarly undervalue the resources required to perform CCTA and possibly decrease access to the procedure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:G.D.R. is an advisor to HeartFlow, outside the submitted work. C. B. gave a lecture in 2019 for HeartFlow, outside the submitted work. B.B.G. is supported by institutional grants to his institution from Siemens Healthineers and the NIH, outside the submitted work. No interests or disclosures declared for M.E.Z., J.C.B., M.G.R., R.B., G.E.W., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The majority of research on sleep and cognition has focused on mean markers of sleep across multiple nights; however, variable sleep patterns have become increasingly common in the modern era. The purpose of this study was to examine whether objective intraindividual variability in sleep quantity and quality are related to verbal and visuospatial learning and memory functioning in young adults., Methods: A total of 218 young adult college students were recruited from a university in the Eastern United States, among which 187 participants (70.6% female; mean age = 20.5, SD = 1.5) had complete actigraphy and cognitive performance data. Objective intraindividual means and variabilities of sleep quantity (total sleep time) and sleep quality (percent wake after sleep onset) were measured over a 1- to 2-week timeframe using wrist actigraphy. Verbal and visuospatial learning and memory were assessed using the International Shopping List and Groton Maze Learning tests of the Cogstate computerized test battery., Results: Greater intraindividual variability in actigraphy-derived sleep quality was associated with poorer visuospatial learning and memory performance after controlling for mean sleep quality and visuomotor attention and processing speed (ps < 0.05). Actigraphic measures of sleep quantity were not related to any learning and memory measures., Conclusion: In young adults, intraindividual variability in objective sleep quality was significantly related to visuospatial learning and memory, over and above mean sleep quality. Given these associations, future studies should aim to identify modifiable lifestyle and environmental factors contributing to variable sleep quality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The benefits of athletic activity may be attenuated by sport-related head impacts, including soccer-related concussion and subconcussive events. The purpose of this study is to characterize the specific effects of soccer heading on white matter microstructure and cognitive function, independent of concussion, relative to non-athlete controls and relative to active athletes who are not involved in collision sports. 246 amateur soccer players, 72 non-contact/non-collision sports athletes and 110 healthy,non-athlete controls were included in the study, and underwent cognitive testing and 3T diffusion tensor imaging (DTI). Voxelwise linear regression, comparing soccer players and non-contact/non-collision sports athletes healthy,non-athlete controls, identified regions of abnormally low and high fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in athlete participants. Generalized estimating equations were used to examine the effects of 2 week and 1 year heading exposure quartile on cognitive performance and on the volume of each high and each low DTI parameter. Athletes with no or lower exposure to repetitive heading exhibited greater expression of low RD, greater expression of high FA and better performance on tasks of attention, processing speed, verbal memory, and working memory compared to non-athletes. Soccer players with the highest exposure to repetitive head impacts, however, did not differ significantly from healthy, non-athletes on either micro-structural features or cognitive performance, findings not explained by concussion history or demographic factors. These results are consistent with the notion that beneficial effects of athletic conditioning or training on brain structure and function may be attenuated by exposure to repeated subconcussive head impacts.

Mutations and variants in the glucocerebrosidase ( GBA ) gene are among the most common genetic risk factors for the development of Parkinson's disease (PD). Yet, penetrance is markedly reduced, and less is known about the burden of carrying a single mutation among those without diagnosed PD. Motor, cognitive, psychiatric, and olfactory functioning were assessed in 30 heterozygous GBA mutation carriers without PD (the majority of whom had mild GBA mutations) and 49 non-carriers without PD. Study focus was on domains affected in GBA mutation carriers with PD, as well as those previously shown to be abnormal in GBA mutation carriers without PD. GBA mutation carriers showed poorer performance on the Stroop interference measure of executive functioning when controlling for age. There were no group differences in verbal memory, Montreal Cognitive Assessment (MoCA), overall motor score, or presence of REM sleep behavior disorder or depression. Although total olfaction scores did not differ, GBA mutation carriers with hyposmia had lower global cognition scores than those without hyposmia. As anticipated by the low penetrance of GBA mutations, these findings suggest that pre-manifest non-motor or motor features of PD may not present in most GBA mutation carriers. However, there is support that there may be a subtle difference in executive functioning among some non-manifesting heterozygous GBA mutation carriers, and, combined with olfaction, this may warrant additional scrutiny as a potential biomarker for pre-manifest and pre-clinical GBA related PD., Competing Interests: SB and RS-P have received consulting fees from Denali Therapeutics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Moran, Bressman, Ortega, Raymond, Nichols, Palmese, Elango, Swan, Shanker, Perera, Wang, Zimmerman and Saunders-Pullman.)

Introduction: There is an urgent need to validate telephone versions of widely used general cognitive measures, such as the Montreal Cognitive Assessment (T-MoCA), for remote assessments., Methods: In the Einstein Aging Study, a diverse community cohort (n = 428; mean age = 78.1; 66% female; 54% non-White), equivalence testing was used to examine concordance between the T-MoCA and the corresponding in-person MoCA assessment. Receiver operating characteristic analyses examined the diagnostic ability to discriminate between mild cognitive impairment and normal cognition. Conversion methods from T-MoCA to the MoCA are presented., Results: Education, race/ethnicity, gender, age, self-reported cognitive concerns, and telephone administration difficulties were associated with both modes of administration; however, when examining the difference between modalities, these factors were not significant. Sensitivity and specificity for the T-MoCA (using Youden's index optimal cut) were 72% and 59%, respectively., Discussion: The T-MoCA demonstrated sufficient psychometric properties to be useful for screening of MCI, especially when clinic visits are not feasible., Competing Interests: The authors report no competing interests., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Objective: In soccer, unintentional and intentional (heading) head impacts are associated with concussive symptoms and cognitive dysfunction. We examined whether personality traits were associated with these behaviors in soccer players., Design: Cross-sectional study., Setting and Participants: Participants completed study visits at the Albert Einstein College of Medicine. A total of 307 adult amateur soccer players, recruited from New York City and the surrounding area, completed 737 HeadCount-2w questionnaires., Predictor Variables: Personality traits (intellect/imagination, conscientiousness, extraversion, agreeableness, and neuroticism) were assessed with the Mini-International Personality Item Pool questionnaire at the baseline study visit., Main Outcome Measures: Participants completed an online questionnaire (HeadCount-2w) to ascertain frequency of intentional head impacts and occurrence of unintentional head impacts every 3 to 6 months. Generalized estimating equations repeated-measures regressions determined whether personality predicted unintentional and intentional impacts., Results: Personality traits were not associated with unintentional head impact(s) or frequency of intentional head impacts., Conclusions: These findings have important clinical implications, suggesting that personality is not driving the association between high levels of unintentional and intentional head impacts and worse neuropsychological functioning and concussive symptoms.

Small vessel cerebrovascular disease, visualized as white matter hyperintensities on T2-weighted magnetic resonance imaging, contributes to the clinical presentation of Alzheimer's disease. However, the extent to which cerebrovascular disease represents an independent pathognomonic feature of Alzheimer's disease or directly promotes Alzheimer's pathology is unclear. The purpose of this study was to examine the association between white matter hyperintensities and plasma levels of tau and to determine if white matter hyperintensities and tau levels interact to predict Alzheimer's disease diagnosis. To confirm that cerebrovascular disease promotes tau pathology, we examined tau fluid biomarker concentrations and pathology in a mouse model of ischaemic injury. Three hundred ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (74.5 ± 7.1 years of age) were included in this cross-sectional analysis. Participants had measurements of plasma total-tau, cerebrospinal fluid beta-amyloid, and white matter hyperintensities, and were diagnosed clinically as Alzheimer's disease ( n  = 97), mild cognitive impairment ( n  = 186) or cognitively normal control ( n  = 108). We tested the relationship between plasma tau concentration and white matter hyperintensity volume across diagnostic groups. We also examined the extent to which white matter hyperintensity volume, plasma tau, amyloid positivity status and the interaction between white matter hyperintensities and plasma tau correctly classifies diagnostic category. Increased white matter hyperintensity volume was associated with higher plasma tau concentration, particularly among those diagnosed clinically with Alzheimer's disease. Presence of brain amyloid and the interaction between plasma tau and white matter hyperintensity volume distinguished Alzheimer's disease and mild cognitive impairment participants from controls with 77.6% and 63.3% accuracy, respectively. In 63 Alzheimer's Disease Neuroimaging Initiative participants who came to autopsy (82.33 ± 7.18 age at death), we found that higher degrees of arteriosclerosis were associated with higher Braak staging, indicating a positive relationship between cerebrovascular disease and neurofibrillary pathology. In a transient middle cerebral artery occlusion mouse model, aged mice that received transient middle cerebral artery occlusion, but not sham surgery, had increased plasma and cerebrospinal fluid tau concentrations, induced myelin loss, and hyperphosphorylated tau pathology in the ipsilateral hippocampus and cerebral hemisphere. These findings demonstrate a relationship between cerebrovascular disease, operationalized as white matter hyperintensities, and tau levels, indexed in the plasma, suggesting that hypoperfusive injury promotes tau pathology. This potential causal association is supported by the demonstration that transient cerebral artery occlusion induces white matter damage, increases biofluidic markers of tau, and promotes cerebral tau hyperphosphorylation in older-adult mice., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: Soccer is the most popular sport worldwide and is the only sport where athletes purposely use their head to deflect the ball during play, termed "heading" the ball. These repetitive head impacts (RHI) are associated with worse neuropsychological function; however, factors that can increase risk of injury following exposure to such head impacts have been largely unexamined. The present study provided a novel examination of the modifying role of sleep on the relationship between RHI exposure and neuropsychological function in college-age soccer players., Methods: Fifty varsity and intramural college soccer players completed questionnaires assessing recent and long-term heading exposure, a self-report measure of sleep function, and a battery of neuropsychological tests., Results: A high level of recent heading exposure was significantly associated with poorer processing speed, independent of concussion history. With reduced sleep duration, a high level of recent heading exposure was related to worse sustained attention. However, with greater hours of sleep duration, heading exposure was related to preserved neuropsychological outcome in sustained attention., Conclusions: We replicated our earlier finding of an association between recent head impact exposure and worse processing speed in an independent sample. In addition, we found that sleep may serve as a risk or protective factor for soccer players following extensive exposure to head impacts. Ultimately, this study furthers the understanding of factors impacting neuropsychological function in soccer players and provides empirical support for sleep interventions to help ensure safer soccer play and recovery from injury.

Objective: To provide a step-by-step guide for performing in-office transperineal prostate biopsy using biplanar ultrasound guidance., Patients and Methods: Biopsies are performed using a freehand technique with the PrecisionPoint Transperineal Access System (Perineologic, Cumberland, MD). This disposable needle guide includes 3 components: a rail/clamp subassembly, a needle carriage with 5 aperture holes, and a 15 gauge access needle. The device is clamped to a side-fire biplanar ultrasound probe, ensuring alignment of the biopsy needle with the probe's ultrasound arrays. Once the patient is sufficiently anesthetized using 1% lidocaine, the access needle is engaged into the perineal skin. This allows for multiple passes of the biopsy needle through a common puncture site. A separate puncture is made for each side of the prostate and the aperture hole is chosen based on the overall height of the prostate. Biopsies are taken using a disposable 18 gauge biopsy gun., Results: The presented video details our approach for performing transperineal prostate biopsy under local anesthesia. Biopsies are performed in the office setting without the need for periprocedural antibiotics. The PrecisionPoint Transperineal Access System ensures proper alignment of the biopsy needle with the ultrasound probe, while minimizing the number of individual needle sticks to the perineal skin. The use of biplanar ultrasound makes it possible to guide the biopsy needle with excellent precision to virtually any area of the prostate. The descried technique can be used for systematic biopsies as well as for targeted biopsies using cognitive fusion with magnetic resonance imaging., Conclusion: We provide a step-by-step guide for performing in-office transperineal prostate biopsy. The presented technique minimizes the risk of infectious complications by eliminating the need for biopsy needles to pass through the rectal mucosa. Biopsies are performed without the need for periprocedural antibiotics, thus furthering the goals of antibiotic stewardship., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? Cross-sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co-morbidities, depression and anxiety were used as co-variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z-scores. Sleep problems were associated with two or more complaints: WHICAP: β = 1.93 (95% confidence interval: 1.59-2.34), p ≤ .0001; HELIAD: β = 1.48 (95% confidence interval: 1.20-1.83), p ≤ .0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints., (© 2018 European Sleep Research Society.)

Prostate cancer is most commonly imaged through a combination of magnetic resonance imaging, x-ray computed tomography, and 99m Tc-methylene diphosphonate bone scan. These conventional imaging modalities, however, suffer from limited sensitivity and specificity for the detection of disease. This can lead to disease understaging and the improper selection of treatment. To address this problem, a variety of novel radiotracers for positron emission tomography (PET) imaging have been developed. This includes agents that accumulate on the basis of alterations in cellular metabolism (eg, 11 C-choline and 18 F-FACBC) as well as those that bind to specific proteins (eg, 68 Ga-PSMA-11, 18 F-DCFPyL, 68 Ga-RM2, and 18 F-DHT). In this review, we examine the performance characteristics of these new PET radiotracers for imaging prostate cancer and discuss ways in which PET imaging can offer more precise clinical information to patients and providers.

Objectives: Insomnia is associated with neuropsychological dysfunction. Evidence points to the role of nocturnal light exposure in disrupted sleep patterns, particularly blue light emitted through smartphones and computers used before bedtime. This study aimed to test whether blocking nocturnal blue light improves neuropsychological function in individuals with insomnia symptoms., Methods: This study used a randomized, placebo-controlled crossover design. Participants were randomly assigned to a 1-week intervention with amber lenses worn in wrap-around frames (to block blue light) or a 1-week intervention with clear lenses (control) and switched conditions after a 4-week washout period. Neuropsychological function was evaluated with tests from the NIH Toolbox Cognition Battery at three time points: (1) baseline (BL), (2) following the amber lenses intervention, and (3) following the clear lenses intervention. Within-subjects general linear models contrasted neuropsychological test performance following the amber lenses and clear lenses conditions with BL performance., Results: Fourteen participants (mean(standard deviation, SD): age = 46.5(11.4)) with symptoms of insomnia completed the protocol. Compared with BL, individuals performed better on the List Sorting Working Memory task after the amber lenses intervention, but similarly after the clear lenses intervention (F = 5.16; p = .014; η2 = 0.301). A similar pattern emerged on the Pattern Comparison Processing Speed test (F = 7.65; p = 0.002; η2 = 0.370). Consideration of intellectual ability indicated that treatment with amber lenses "normalized" performance on each test from approximately 1 SD below expected performance to expected performance., Conclusions: Using a randomized, placebo-controlled crossover design, we demonstrated improvement in processing speed and working memory with a nocturnal blue light blocking intervention among individuals with insomnia symptoms. (JINS, 2019, 25, 668-677).

Background: We hypothesized that higher quality of life would be associated with better cognitive function and a reduced risk of incident all cause dementia and Alzheimer disease (AD) in older adults., Materials and Methods: Participants included 1183 older adults with an average age of 78.2 (SD=5.3) from Einstein Aging Study. The 36-Item Short-Form Health Survey was used to measure health-related quality of life (HRQoL). We investigated baseline associations between the cognitive domains of memory, executive function, and general fluid ability with 8 subscales of the 36-Item Short-Form Health Survey (physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, social functioning, role limitations due to emotional problems, vitality, and general mental health) and the 2 component summary scores of physical component summary (PCS) and mental component summary (MCS). Next, we used Cox proportional hazard models to assess the predictive validity of HRQoL subscales for the onset of incident dementia and incident AD., Results: At baseline, higher scores (better HRQoL) on MCS and its 4 subscales (social functioning, role limitations due to emotional problems, vitality, and general mental health) were associated with higher performance on both memory and executive function domains. Higher scores in role limitation due to physical problems, role limitation due to emotional problems, and general mental health subscales were associated with reduced risk of incident dementia. Higher MCS, but not PCS, predicted a reduced incident of all-cause dementia and AD., Conclusions: These findings suggest that diminution of HRQoL precedes the onset of diagnosable dementia and may be useful in the prediction of dementia onset.

Background:: There is increasing evidence that depressive symptoms are associated with increased risk of cognitive impairment and dementia in older adults. In current study, we aimed to investigate the effect of depressive symptoms on incident Alzheimer disease and all-cause dementia in a community sample of older adults., Methods:: Participants were 1219 older adults from the Einstein Aging Study, a longitudinal cohort study of community-dwelling older adults in Bronx County, New York. The Geriatric Depression Scale (GDS, 15-item) was used as a measure of depressive symptoms. The primary outcome was incident dementia diagnosed using the Diagnostic and Statistical Manual, Fourth Edition, criteria. Cox proportional hazard models were used to estimate the risk of incident dementia as a function of GDS score for the whole population and also for 2 different time intervals, <3 years and ≥3 years after baseline assessment., Results:: Among participants, 132 individuals developed dementia over an average 4.5 years (standard deviation [SD] = 3.5) of follow-up. Participants had an average age of 78.3 (SD = 5.4) at baseline, and 62% were women. Among all participants, after controlling for demographic variables and medical comorbidities, a 1-point increase in GDS was associated with higher incidence of dementia (hazard ratio [HR] = 1.11, P = .007). After up to 3 years of follow-up, depressive symptoms were not significantly associated with dementia incidence (HR = 1.09; P = .070). However, after more than 3 years, GDS score was a significant predictor of incident dementia (HR = 1.13, P = .028)., Conclusions:: Our results suggest that depressive symptoms are associated with an increased risk of incident dementia in older adults.

Background: Chronic pain is common among older adults and is associated with cognitive dysfunction based on cross-sectional studies. However, the longitudinal association between chronic pain and incident dementia in community-based samples is unknown., Objective: We aimed to evaluate the association of pain intensity and pain interference with incident dementia in a community-based sample of older adults., Methods: Participants were 1,114 individuals 70 years of age or older from Einstein Aging Study (EAS), a longitudinal cohort study of community-dwelling older adults in the Bronx County, NY. The primary outcome measure was incident dementia, diagnosed using DSM-IV criteria. Pain intensity and interference in the month prior to first annual visit were measured using items from the SF-36 questionnaire. Pain intensity and pain interference were assessed as predictors of time to incident dementia using Cox proportionate hazards models while controlling for potential confounders., Results: Among participants, 114 individuals developed dementia over an average 4.4 years (SD=3.1) of follow-up. Models showed that pain intensity had no significant effect on time to developing dementia, whereas higher levels of pain interference were associated with a higher risk of dementia. In the model that included both pain intensity and interference as predictors of incident dementia, pain interference had a significant effect on incident dementia, and pain intensity remained non-significant., Conclusion: As a potential remediable risk factor, the mechanisms linking pain interference to cognitive decline merit further exploration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To investigate the role of grain boundary pinning and the mechanisms by which phase mixing occurs during deformation of polymineralic rocks, we conducted high-strain torsion experiments on samples consisting of olivine plus 30 vol% ferropericlase. Experiments were performed in a gas-medium deformation apparatus at 1524 K and 300 MPa. Samples were deformed to outer radius shear strains of up to γ ( R ) = 14.1. The value of the stress exponent and the small grain sizes of our samples indicate that our two-phase material deformed by dislocation-accommodated grain boundary sliding. In samples deformed to 1 <  γ  < 7, elongated clusters of ferropericlase grains form thin layers in the olivine matrix, and small grains of ferropericlase appear at olivine grain boundaries and three- and four-grain junctions. By γ  ≈ 14, a well-distributed mixture of small ferropericlase grains among the olivine grains developed. Microstructures exhibit similarities to both mechanical and chemical models proposed to describe the processes leading to phase mixing. Our results provide evidence for grain size reduction during phase mixing that results in a grain size significantly smaller than the value predicted by the single-phase recrystallization piezometer for olivine. Thus, phase mixing provides a mechanism for the persistent weakening of rocks that is important for developing and maintaining shear zones necessary for plate tectonics.This article is part of a discussion meeting issue 'Earth dynamics and the development of plate tectonics'., (© 2018 The Author(s).)

The effects of soccer-related head impacts, beyond overt concussions, on Patient Reported Outcomes (PROs) have not been explored to date. Generalized estimating equations were employed to determine the association between soccer-related head impacts (headers in the prior 2 weeks, unintentional head impacts in the prior 2 weeks, headers in the prior 12 months and lifetime concussions) on PROs including depression, anxiety, sleep disturbance and sleep impairment. Compared to players with no unintentional head impacts in the prior 2 weeks, players with one unintentional exposure reported more symptoms of anxiety (p = 0.002) and players with 2+ exposures reported more symptoms of depression (p = 0.006) and anxiety (p < 0.001). In contrast, players in the 3rd Quartile of 12 mo. headers reported less anxiety (p = 0.001), sleep disturbance (p = 0.002) and sleep impairment (p < 0.001) compared to those in the 1st quartile. Unintentional head impacts are associated with worse PROs while more headers are paradoxically associated with better PROs.

Introduction: White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer's disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD., Participants and Methods: Participants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds., Results: Mutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds., Discussion: Although there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.

Objective: Compared to heading, unintentional head impacts (e.g., elbow to head, head to head, head to goalpost) in soccer are more strongly related to risk of moderate to very severe Central Nervous System (CNS) symptoms. But, most head impacts associated with CNS symptoms that occur in soccer are mild and are more strongly related to heading. We tested for a differential relation of heading and unintentional head impacts with neuropsychological (NP) test performance., Method: Active adult amateur soccer players were recruited in New York City and the surrounding areas for this repeated measures longitudinal study of individuals who were enrolled if they had 5+ years of soccer play and were active playing soccer 6+ months/year. All participants completed a baseline validated questionnaire ("HeadCount-2w"), reporting 2-week recall of soccer activity, heading and unintentional head impacts. In addition, participants also completed NP tests of verbal learning, verbal memory, psychomotor speed, attention, and working memory. Most participants also completed one or more identical follow-up protocols (i.e., HeadCount-2w and NP tests) at 3- to 6-month intervals over a 2-year period. Repeated measures General Estimating Equations (GEE) linear models were used to determine if variation in NP tests at each visit was related to variation in either heading or unintentional head impacts in the 2-week period before testing., Results: 308 players (78% male) completed 741 HeadCount-2w. Mean (median) heading/2-weeks was 50 (17) for men and 26 (7) for women. Heading was significantly associated with poorer performance on psychomotor speed ( p  < 0.001) and attention ( p  = 0.02) tasks and was borderline significant with poorer performance on the working memory ( p  = 0.06) task. Unintentional head impacts were not significantly associated with any NP test. Results did not differ after excluding 22 HeadCount-2w with reported concussive or borderline concussive symptoms., Conclusion: Poorer NP test performance was consistently related to frequent heading during soccer practice and competition in the 2 weeks before testing. In contrast, unintentional head impacts incurred during soccer were not related to cognitive performance.

Objectives: The present study examined the relative contribution of recent or long-term heading to neuropsychological function in amateur adult soccer players., Participants and Methods: Soccer players completed a baseline questionnaire (HeadCount-12m) to ascertain heading during the prior 12 months (long-term heading, LTH) and an online questionnaire (HeadCount-2w) every 3 months to ascertain heading during the prior 2 weeks (recent heading, RH). Cogstate, a battery of six neuropsychological tests, was administered to assess neuropsychological function. Generalized estimating equations were used to test if LTH or RH was associated with neuropsychological function while accounting for the role of recognized concussion., Results: A total of 311 soccer players completed 630 HeadCount-2w. Participants had an average age of 26 years. Participants headed the ball a median of 611 times/year (mean=1,384.03) and 9.50 times/2 weeks (mean=34.17). High levels of RH were significantly associated with reduced performance on a task of psychomotor speed (p=.02), while high levels of LTH were significantly associated with poorer performance on tasks of verbal learning (p=.03) and verbal memory (p=.04). Significantly better attention (p=.02) was detectable at moderately high levels of RH, but not at the highest level of RH. One hundred and seven (34.4%) participants reported a lifetime history of concussion, but this was not related to neuropsychological function and did not modify the association of RH or LTH with neuropsychological function., Conclusion: High levels of both RH and LTH were associated with poorer neuropsychological function, but on different domains. The clinical manifestations following repetitive exposure to heading could change with chronicity of exposure. (JINS, 2018, 24, 147-155).

Background: The Memory Binding Test (MBT) demonstrated good cross-sectional discriminative validity and predicted incident aMCI., Objective: To assess whether the MBT predicts incident dementia better than a conventional list learning test in a longitudinal community-based study., Methods: As a sub-study in the Einstein Aging Study, 309 participants age≥70 initially free of dementia were administered the MBT and followed annually for incident dementia for up to 13 years. Based on previous work, poor memory binding was defined using an optimal empirical cut-score of≤17 on the binding measure of the MBT, Total Items in the Paired condition (TIP). Cox proportional hazards models were used to assess predictive validity adjusting for covariates. We compared the predictive validity of MBT TIP to that of the free and cued selective reminding test free recall score (FCSRT-FR; cut-score:≤24) and the single list recall measure of the MBT, Cued Recalled from List 1 (CR-L1; cut-score:≤12)., Results: Thirty-five of 309 participants developed incident dementia. When assessing each test alone, the hazard ratio (HR) for dementia was significant for MBT TIP (HR = 8.58, 95% CI: (3.58, 20.58), p < 0.0001), FCSRT-FR (HR = 4.19, 95% CI: (1.94, 9.04), p = 0.0003) and MBT CR-L1 (HR = 2.91, 95% CI: (1.37, 6.18), p = 0.006). MBT TIP remained a significant predictor of dementia (p = 0.0002) when adjusting for FCSRT-FR or CR-L1., Conclusions: Older adults with poor memory binding as measured by the MBT TIP were at increased risk for incident dementia. This measure outperforms conventional episodic memory measures of free and cued recall, supporting the memory binding hypothesis.

Background: The relation of pre-dementia stages to mortality has not been fully explored. Previous work examining subjective cognitive decline (SCD) and mortality is limited and mixed regarding methods used and consistency of findings., Objective: To examine SCD and mortality in a longitudinal, community-based cohort, using item response theory (IRT) methodology to form a composite SCD measure. Also, to assess whether this relationship was independent of clinical cognitive status., Methods: The Einstein Aging Study is a diverse longitudinal cohort of adults aged ≥70. SCD items were extracted from baseline CERAD questionnaires and a composite score was formed using IRT methodology. A total of 1,741 participants with complete data were clinically diagnosed as cognitively normal, or as having amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), or dementia. 645 deaths occurred over a period of 8,912 person-years of follow-up. Cox proportional hazard models predicted time to death adjusting for covariates., Results: A one standard deviation unit increase in level of SCD was associated with >20% higher risk of mortality. However, when models were adjusted for clinical cognitive status, the association was no longer significant. Both dementia and aMCI predicted mortality. Furthermore, when analyses focused only on those without cognitive impairment, SCD level did not predict mortality., Conclusions: The association of SCD with mortality may be due to the association of SCD with clinical cognitive status. Thus, SCD may be used as a community-based screen to initially identify those with cognitive impairment who may be at greatest risk for death.

Background: In this study we investigated the role of hippocampal volume (HV) in visual memory., Methods: Participants were a subsample of older adults (> = 70 years) from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF) copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks., Results: Participants' (n = 113, mean age = 78.9 years) average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001) and left (β = 0.031, p = 0.001) and right HVs (β = 0.24, p = 0.012). CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025) and the CF copy task (β = 0.30, p = 0.009) in the model. CF copy did not show any significant associations with HV., Conclusion: Our results suggest that left HV contributes in retrieval of visual memory in older adults.

Mutations in the glucocerebrosidase (GBA) gene are a strong genetic risk factor for the development of Parkinson's disease and dementia with Lewy Bodies. However the penetrance of GBA mutations is low for these diseases in heterozygous carriers. The aim of this study was to examine the relationship between mutation status and cognitive and motor functioning in a sample of community-dwelling older adults. Using linear mixed effects models, we examined the effect of heterozygous mutation status on 736 community-dwelling older adults (≥70 years) without dementia or Parkinson's disease assessed over an average of 6 years, 28 of whom had a single GBA mutation (primarily N370S). Verbal memory was measured using the picture version of the Free and Cued Selective Reminding Test, and carriers showed significantly (p < 0.05) greater decline in verbal memory over time. There was no difference in motor function or any other cognitive domain. Taken together, these results suggest an effect, but an overall limited burden, of harboring a single GBA mutation in aging mutation carriers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To examine the cross-sectional associations of the separate subscales of the Perceived Stress Scale (PSS) and tests measuring cognitive domains in older adults., Methods: 897 adults over the age of 70 free of amnestic mild cognitive impairment and dementia and enrolled in the Einstein Aging Study made up the study sample. The PSS-14 was used to measure stress. Three cognitive domains (language, episodic memory, and frontal-executive) had previously been found using principle component analysis. Linear regression analyses were used to determine the relationship between the PSS subscales and cognitive domain function., Results: The study sample had a mean age of 79.1 years and 62.8% were female. Bivariate correlations show that the PSS-14 positively worded subscale of the PSS (PSS-PW) was significantly associated with all three cognitive domains (language: r = -0.15, p < 0.001; episodic memory: r = -0.16, p < 0.001; frontal-executive: r = -0.21, p <0.001) while the negatively worded subscale of the PSS (PSS-NW) was not significantly associated with any cognitive domain. In linear regression analyses adjusted for age, white race, gender, years of education, and depressive symptoms, the PSS-PW remained significantly associated with each of the cognitive domains. The PSS-NW was not associated with any cognitive domains in any model. The PSS-14 was significantly associated with language and episodic memory, but not the frontal-executive domain., Conclusion: Worse PSS-PW scores are associated with reduced cognitive function in the executive, memory, and language domains in nondemented older adults. The PSS-PW subscale correlated better with cognitive function than the overall PSS-14. Future research should evaluate the temporality of the association and if stress reduction therapies improve cognitive performance.

Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS ( n = 11) and control subjects ( n = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus ( p = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η 2 = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r = -0.50, p = 0.008) and a greater arousal index ( r = -0.44, p = 0.017). OSAS did not significantly affect neuropsychological measures ( p values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity ( r = 0.54, p = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS. SIGNIFICANCE STATEMENT In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children., (Copyright © 2017 the authors 0270-6474/17/374280-09$15.00/0.)

Objective: To determine the rate and differential contribution of heading vs unintentional head impacts (e.g., head to head, goal post) to CNS symptoms in adult amateur soccer players., Methods: Amateur soccer players completed baseline and serial on-line 2-week recall questionnaires (HeadCount) and reported (1) soccer practice and games, (2) heading and unintentional soccer head trauma, and (3) frequency and severity (mild to very severe) of CNS symptoms. For analysis, CNS symptoms were affirmed if one or more moderate, severe, or very severe episodes were reported in a 2-week period. Repeated measures logistic regression was used to assess if 2-week heading exposure (i.e., 4 quartiles) or unintentional head impacts (i.e., 0, 1, 2+) were associated with CNS symptoms., Results: A total of 222 soccer players (79% male) completed 470 HeadCount questionnaires. Mean (median) heading/2 weeks was 44 (18) for men and 27 (9.5) for women. One or more unintentional head impacts were reported by 37% of men and 43% of women. Heading-related symptoms were reported in 20% (93 out of 470) of the HeadCounts. Heading in the highest quartile was significantly associated with CNS symptoms (odds ratio [OR] 3.17, 95% confidence interval [CI] 1.57-6.37) when controlling for unintentional exposure. Those with 2+ unintentional exposures were at increased risk for CNS symptoms (OR 6.09, 95% CI 3.33-11.17) as were those with a single exposure (OR 2.98, 95% CI 1.69-5.26) when controlling for heading., Conclusions: Intentional (i.e., heading) and unintentional head impacts are each independently associated with moderate to very severe CNS symptoms., (© 2017 American Academy of Neurology.)

Introduction: Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer's disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults., Methods: This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume., Results: Participants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, p<0.002) and FCSRT Delayed Recall (β=0.20, p=0.025)., Conclusions: Our findings confirm previous research on the specific roles of CA1 and subiculum in episodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The Perceived Stress Scale (PSS) is made up of two subscales but is typically used as a single summary measure. However, research has shown that the two subscales may have differential properties in older adults., Objective: To evaluate the internal consistency, test-retest reliability, and the concurrent and predictive validity for development of amnestic mild cognitive impairment (aMCI) of the positively-worded (PSS-PW) and negatively-worded (PSS-NW) subscale scores of the PSS in older adults., Methods: We recruited community residing older adults free of dementia from the Einstein Aging Study. Reliability of the PSS-PW and PSS-NW was assessed using Cronbach's alpha for internal consistency and intraclass correlation for one year test-retest reliability. Concurrent validity was evaluated by examining the relationship between the PSS subscales and depression, anxiety, neuroticism, and positive and negative affect. Predictive validity was assessed using multivariate Cox regression analyses to examine the relationship between baseline PSS-PW and PSS-NW score and subsequent onset of aMCI., Results: Both PSS-PW and PSS-NW showed adequate internal consistency and retest reliabilities. Both the PSS-PW and PSS-NW were associated with depression, neuroticism, and negative affect. The PSS-NW was uniquely associated with anxiety while the PSS-PW was uniquely associated with positive affect. Only the PSS-PW was associated with a statistically significant increased risk of incident aMCI (HR = 1.27; 95% CI: 1.06-1.51 for every 5-point increase in PSS-PW)., Conclusions: Evaluating the separate effects of the two PSS subscales may reveal more information than simply using a single summation score. Future research should investigate the PSS-PW and PSS-NW as separate subscales.

The hippocampus plays a critical role in verbal and spatial memory, thus any pathological damage to this formation may lead to cognitive impairment. It is suggested that right and left hippocampi are affected differentially in healthy or pathologic aging. The purpose of this study was to test the hypothesis that verbal episodic memory performance is associated with left hippocampal volume (HV) while spatial memory is associated with right HV. 115 non-demented adults over age 70 were drawn from the Einstein Aging Study. Verbal memory was measured using the free recall score from the Free and Cued Selective Reminding Test - immediate recall (FCSRT-IR), logical memory immediate and delayed subtests (LM-I and LM-II) from the Wechsler Memory Scale-Revised (WMS-R). Spatial Memory was measured using a computerized dot memory paradigm that has been validated for use in older adults. All participants underwent 3T MRI with subsequent automatized measurement of the volume of each hippocampus. The sample had a mean age of 78.7 years (SD=5.0); 57% were women, and 52% were white. Participants had a mean of 14.3 years (SD=3.5) of education. In regression models, two tests of verbal memory (FCSRT-IR free recall and LM-II) were positively associated with left HV, but not with right HV. Performance on the spatial memory task was associated with right HV, but not left HV. Our findings support the hypothesis that the left hippocampus plays a critical role in episodic verbal memory, while right hippocampus might be more important for spatial memory processing among non-demented older adults., (Copyright © 2016 Elsevier Ltd. All rights reserved.)