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Background: Visual impairment could worsen sleep/wake disorders and cognitive decline. Objective: To examine interrelations among self-reported visual impairment, sleep, and cognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Miami-site. Method: HCHS/SOL Miami-site participants ages 45–74 years (n = 665) at Visit-1, who returned for cognitive test 7-years later (SOL-INCA). Participants completed the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ), validated sleep questionnaires and test for obstructive sleep apnea (OSA) at Visit-1. We obtained verbal episodic learning and memory, verbal fluency, processing speed, and executive functioning at Visit-1 and at SOL-INCA. Processing speed/executive functioning were added to SOL-INCA. We examined global cognition and change using a regression-based reliable change index, adjusting for the time lapse between Visit-1 and SOL-INCA. We used regression models to test whether 1) persons with OSA, self-reported sleep duration, insomnia, and sleepiness have an increased risk for visual impairment, 2a) visual impairment is associated with worse cognitive function and/or decline, and 2b) sleep disorders attenuate these associations. Result: Sleepiness (β= 0.04; p

Background: Frailty is directly linked to physical robustness and cognitive decline in older age. The Fried Frailty phenotype (FP) is a construct composed of five core symptoms that has been studied predominately in older age. There is little research contrasting the psychometric properties of the FP in mid-life versus older age. Objective: We compared the psychometric properties of the FP in mid-life and older age and investigated relationships between the FP and cognition. Methods: Frailty and neuropsychological assessments were completed on 361 adults, between 45 and 92 years of age, without primary neurological disorders. Confirmatory factor analysis was used to examine FP, indicated by Grip Strength, Gait Speed, Physical Activity, Fatigue, and Weight Loss. Measurement invariance was tested in mid-life (45–64 years) versus older age (≥65 years). Associations were examined between FP and language, executive functions, memory, processing speed, and visuospatial domains as well as a Generalized Cognition factor. Age was tested as a moderator of these associations. Results: Weight Loss was a poor indicator of FP. Factor loadings were comparable across age groups; however, Fatigue was disproportionately higher among those in mid-life. FP was negatively associated with all cognitive domains and remained invariant across age groups. Conclusion: Results support the construct validity of the FP and document its stable associations with poorer cognition in middle and older life. Future research investigating central features of frailty earlier in life may offer avenues for developing targeted prevention measures and better characterization of individuals with elevated dementia risk.

IntroductionWe aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N=5500) in different age and sex groups.MethodsThe exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (

Objective Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. Methods Forty-eight non-demented middle-aged and older adults ( Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. Results Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (β = −.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (β = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue ( r = −.43, P = .003) and TMT B-A (β = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. Conclusion This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

This study examined the association between self-reported fatigue and neuropsychological performance in 167 middle-aged and older (age range: 50-91 years) adults without dementia. Participants completed the Fatigue Symptom Inventory, a comprehensive neuropsychological evaluation, and frailty assessment. Higher levels of fatigue were significantly associated with poorer attention/information processing, executive functioning, and psychomotor speed, even after controlling for depression, sleep quality, physical weakness, and other covariates. Participants endorsing moderate-severe fatigue faced higher odds (

Introduction We aim to determine if white matter hyperintensities and decreased brain volumes are associated with sleep-disordered breathing (SDB), in a diverse sample of middle-aged and older Hispanic/Latino adults. Methods Our sample of 1,119 Hispanics/Latinos (ages older than 50-years; 70% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent brain magnetic resonance imaging (MRI) as part of the Study of Latinos - Investigation of Neurocognitive Aging MRI (SOL-INCA MRI) ancillary study. MRI outcomes of interest included global (gray matter, total brain) and regional (lobar cortices, hippocampus) brain volumes, lateral ventricle volume, and total white matter hyperintensity (WMH) volume. All MRI measures were residualized for total cranial volume. Our main exposure was visit-1 sleep data (2008-2011), which includes information about SDB defined with the respiratory event index 3% (REI), ≥5 and ≥15 (moderate-severe SDB) identified by home-sleep apnea test. Survey linear regression models to assess the association between sleep measures and MRI outcomes adjusted for age, sex, education, Hispanic/Latino background, body mass index, tobacco use, alcohol consumption, and physical activity factors and accounted for HCHS/SOL complex study design. We tested for effect modifications by age, sex and Hispanic/Latino background. Results Mean age was 63.9±7.0 years. Adjusting for age, sex, and education, individuals with a REI ≥15 (vs. Conclusion In a diverse sample of Hispanic/Latinos, moderate-severe SDB was associated with decreased total brain volumes and increments in hippocampal volumes. Our findings suggest that SDB related neuroimaging markers of brain health could serve to identify Hispanic/Latino participants with sleep related Alzheimer’s disease and related dementia risk. Support (If Any) This work is supported by National Institute on Aging (R01AG048642, RF1AG054548, and R01AG063868) and by the National Heart Lung Blood Institute (R01HL098297). Dr. González also receives additional support from P30AG59299. The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-philip glass beck HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements.

Introduction Long and short sleep have been associated with stroke and dementia. Sleep patterns may differ by sex and Hispanic/Latino background. Within Hispanics/Latinos heterogeneity in sleep outcomes exists and is understudied. The purpose of this study was to examine associations between sleep duration and MRI biomarkers of brain health. Methods SOL-Investigation of Neurocognitive Aging (SOL-INCA) MRI study is an ongoing ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our analytic sample consisted of 1,103 adults 50-years and older from diverse Hispanics/Latino backgrounds that completed baseline sleep assessments (2008-2011) and underwent neuroimaging (2018-ongoing; Mean age 64 ±6.9 years). The main exposures were baseline self-reported average nightly sleep duration. Outcomes included brain volume measures residualized for cranial volume (e.g. total brain, hippocampal, and white matter hyperintensities). Brain outcomes were modeled, using regression techniques, as a function of sleep duration and adjusting for age, sex, education, Hispanic/Latino background, language use, self-reported cardiovascular events, BMI, depressive symptoms, Apena/Hypopena index and self-reported sleep quality. Results Mean sleep duration was 7.7 ± 1.36 hours, and 13.2% reported sleeping >9 hours. Increasing sleep duration was associated with smaller total brain (Btotal_brain -1.32 [-2.33 ; -0.32], p Conclusion We found that increments in sleep duration was associated with lower total brain volume and larger ventricle size, MRI measures that could associate with increased dementia-risk in diverse Hispanic/Latino adults. Support (If Any) This work is supported by National Institute on Aging (R01AG048642, RF1AG054548, and R01AG063868) and by the National Heart Lung Blood Institute (R01HL098297). Dr. González also receives additional support from P30AG59299. The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-philip glass beck HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements.

Introduction We determined if actigraphy-derived sleep patterns led to 7-year cognitive decline in middle-aged to older Hispanic/Latino adults. Methods We examined 1035 adults, 45 to 64 years of age, from the Hispanic Community Health Study/Study of Latinos. Participants had repeated measures of cognitive function 7 years apart, home sleep apnea studies, and 1 week of actigraphy. Survey linear regression evaluated prospective associations between sleep and cognitive change, adjusting for main covariates. Results Longer sleep-onset latency was associated with declines in global cognitive function, verbal learning, and verbal memory. Longer sleep-onset latency was also cross-sectionally associated with verbal learning, verbal memory, and word fluency. Sleep fragmentation was not associated with cognitive change. Conclusion In a cohort of mostly middle-aged Hispanic/Latinos, actigraphy-derived sleep-onset latency predicted 7-year cognitive change. These findings may serve as targets for sleep interventions of cognitive decline.

Background Increased risk for the future development of Alzheimer disease begins as early as midlife. Algorithm-based scores, such as the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, and the Framingham general cardiovascular disease (CVD) risk score, have been used to determine future risk for the development of cognitive decline and dementia. We evaluated the association between neuroimaging and cognitive measures with the 2 risk scores in middle-aged, cognitively intact adults (49±6 y). Methods In a cohort of 132 participants collected in 2014, magnetic resonance imaging was used to determine measures of cortical thickness in a priori regions of interest and a neuropsychological battery to assess memory and executive function. Results The CAIDE dementia risk score was significantly and inversely associated with the cortical thickness of the parahippocampal (r=-0.266; P=0.002) and superior frontal gyrus (r=-0.261; P=0.002) despite a considerable percentage of individuals (99.3%) at low risk for CVD. There was a significant negative association between CAIDE and memory (r=-0.251; P=0.003). Framingham general CVD score was not associated with brain structure or cognitive function. Conclusions These results indicate that the CAIDE dementia risk score is associated with cortical thickness and cognitive function at midlife in a low-risk population. These data provide insight into subclinical structural and functional changes occurring during midlife associated with future risk for the development of dementia.

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity-related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.

Introduction Frailty, a multidimensional construct of decreased reserve is an important predictor of functional independence and quality of life in older adults. There is a growing body of evidence highlighting reduced sleep efficiency and sleep duration predicts frailty in older adults. However, the sex differences in these relationships have been understudied. Methods 253 participants (163) ranging in age from 50-92 years (mean= 67.59 years, S.D.= 9.22 years), underwent frailty assessment and completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Statistical moderation was assessed using nonparametric bootstrapping. All models statistically controlled for age, education and depression status. Results Higher scores on the PSQI predicted higher levels of fatigue (β=1.87, 95% CI= 0.48-3.27) and higher grip strength with the left hand (β= 0.81, 95% CI= 0.85-1.53). These relationships were significantly moderated by sex (β=-0.77, p=0.05 & β=-0.52, p=0.01). Specifically, high scores on the PSQI predicted more fatigue stronger grip strength in men (β=1.11, 95% CI=0.41-1.81) and weaker grip strength in women (β=-0.25, 95% CI=-0.51--0.02). There was no association between scores on the ESS and any of the frailty measures. Conclusion The relationships between PSQI scores and measures of fatigue and grip strength were statistically moderated by sex. These differences are not explained by sex differences in overall sleep quality or baseline frailty. This is consistent with the literature emphasizing sex differences in the effects of risk/lifestyle factors. It is possible that the relationship between sleep quality and frailty is altered by additional hormonal factors and warrant further investigation. Support (if any) This research was supported by the Evelyn F. McKnight Brain Research Foundation

Objectives: Excessive adipose tissue, especially in the abdominal area, is associated with increased risk of dementia in older adults. However, the mechanisms underlying this relationship are poorly understood. As increased adiposity is also associated with lower circulating levels of brain-derived neurotrophic factor (BDNF), a key molecule modulating brain plasticity and neuronal regeneration, we hypothesized that the changes in cognition that occur as a result of excessive abdominal adiposity would be driven by lower levels of circulating BDNF. Methods: Fasting blood samples were obtained from 60 participants aged 40–60 years (mean±SD=52.3±5.6) and BDNF levels were assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was measured using a ratio of waist circumference to hip circumference (WHR). Participants also completed a neuropsychological assessment battery to assess executive function. Statistical mediation was assessed using traditional causal steps and nonparametric bootstrapping. Results: Higher WHR was significantly associated with poorer performance on the Controlled Oral Word Association (COWA) letter fluency test (β=−0.489; p=.003) and lower levels of circulating BDNF (β=−0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (β=0.60; 95% confidence interval [−3.79, −0.26]). Conclusions: The relationship between higher WHR and verbal fluency was fully statistically mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable mechanism through which executive function decline occurs in individuals with high abdominal adiposity. BDNF enhancing interventions (physical exercise and dietary restriction) could thus be used to improve executive function in these individuals. (JINS, 2016, 22, 1–8)

Data increasingly points to midlife health and modifiable risk factors as critical targets for improving older-age health outcomes and mitigating potential cognitive impairment and disease. We used biennial Health and Retirement Study data (1998-2016) collected on adults ages 50-64 years who did not meet criteria for dementia at baseline and who remained living by 2016 (unweighted-n=4,803). Cognitive status was defined using Langa-Weir criteria: Normal, Cognitively Impaired Not Dementia (CIND), and Dementia. We examined how 18-year patterns in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) predicted cognitive status in 2016. We used latent class analysis to extract longitudinal phenotypes of activities limitations, followed by survey multinomial logistic regressions to examine their associations with cognitive status and test for race/ethnic modifications. We identified three groups of functional impairment: (1) gradually increasing (15.7%), (2) stable elevated (5.6%), and (3) minimal dysfunction (78.7%). After covariates adjustment, both the gradual and stable elevated impairment groups (vs. minimal) had substantially higher relative risk ratios (RRR) for dementia (RRR=5.71[3.89;8.39] and RRR=7.87[4.23,14.64]) and CIND (RRR=2.21 [1.69,2.88] and RRR=1.92[1.16;3.17]). We detected modifications by race/ethnicity such that Hispanics with stable elevated impairment had a higher probability of dementia compared to their White counterparts. The results varied for Blacks and did not significantly differ from Whites. Data-driven methods may improve our understanding of heterogeneous functional impairment patterns among late middle-aged adults and allow for tailored ADRD prevention strategies. Focused risk-based interventions can yield important public health savings and reductions in structural, social, and individual health burdens.

Introduction We aimed to determine if age or sex modifies associations between sleep-disordered breathing (SDB), sleep duration and severe phenotypes of combined SDB/sleep duration with 7-year neurocognitive change (NC) in a diverse sample of U.S. Hispanic/Latinos. Methods We analyzed data of 5,235 adults 50-80 years of age from SOL-INCA, an ancillary to the Hispanic Community Health Study/Study of Latinos that determines the risk factors for NC. The main outcome was NC after a mean follow-up of 7-years on measures of memory (SEVLT sum and SEVLT recall), language (word fluency), processing speed (DSS) and a cognitive impairment screener. We evaluated the effect of baseline SDB (AHI ≥ 15), sleepiness (Epworth Sleepiness Scale, ESS ≥ 10), self-reported sleep duration (i.e. Results Overall, the mean age was 56.0 years, 54.8% females, 62.2% completed high school, 17.3% had SDB, 6.6% had short sleep,and 14.8% had long sleep. Sleep duration and SDB were not associated with NC. There was a significant interaction between agexSDB+sleep duration on delayed recall (F10,599= 2.40, p=0.01) and processing speed (F10,597= 2.55, p=0.01). Combined SDB + short sleep was associated with decline in processing speed (β=-0.6, 95% CI= [-1.2, -0.1], and combined SDB+long sleep was associated with decline in verbal memory (β=-0.9, 95% CI=[-1.7, -0.2] in adults aged ≥ 65 years. There was no association in participants aged Conclusion Age, but not sex, modified the association between SDB and sleep duration with decline on processing speed and verbal memory. Sleep interventions tailored for older adults may be useful in slowing or preventing neurocognitive decline. Support This work is supported by National Institute on Aging (R01AG048642, RF1AG054548, R01AG061022, and R21AG056952).

Objectives:Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition.Participants:154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included.Measurements:Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures.Results:Frailty severity predicted weaker executive function (B = −2.77, β = −0.30, 95% CI = −4.05 – −1.29) and processing speed (B = −1.57, β = −0.17, 95% CI = −3.10 – −0.16). Poor sleep quality predicted poorer executive function (B = −0.47, β = −0.21, 95% CI = −0.79 – −0.08), processing speed (B = −0.64, β = −0.28, 95% CI = −0.98 – −0.31), learning (B = −0.42, β = −0.19, 95% CI = −0.76 – −0.05) and delayed recall (B = −0.41, β = −0.16, 95% CI = −0.80 – −0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = −0.66, β = −0.07, 95% CI = −1.48 – −0.39), learning (B = −0.85, β = −0.07, 95% CI = −1.85 – −0.12), delayed recall (B = −0.47, β = −0.08, 95% CI = −2.12 – −0.39) and processing speed (B = −0.90, β = −0.09, 95% CI = −1.85 – −0.20).Conclusions:Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.

OBJECTIVE: To investigate the effect of Apolipoprotein E (APOE) genotype on the association between dietary polyunsaturated fat (PUFA), cognitive function, and cerebral glutamate. METHODS: A participant sample of 122 middle-aged adults were grouped according to APOE genotype (ε4 carrier or ε4 non-carrier) and asked to record dietary intake for three consecutive days. All participants also underwent neuropsychological testing and a proton magnetic resonance spectroscopy ((1)H MRS) scan to assess glutamate in the posterior cingulate cortex. RESULTS: Multiple regression analyses revealed a significant interaction between APOE genotype and PUFA intake on memory performance, F(1,113) = 6.749, p = .016. Greater PUFA intake was associated with better memory performance in healthy middle-aged adults who were APOE ε4 non-carriers, but not for ε4 carriers. Furthermore, there was a significant interaction between APOE genotype and PUFA intake on cerebral glutamate, in that dietary PUFA was associated with greater cerebral glutamate in APOE ε4 carriers, but not for ε4 non-carriers, F(1,114) = 5.173, p = .025. CONCLUSIONS: The findings suggest that PUFA action on the brain differs according to APOE polymorphism and points towards cerebral glutamate as a potential marker of genetic risk for Alzheimer’s disease (AD). Early treatment consisting of PUFA supplementation that is tailored to APOE genotype may be an important intervention for the prevention of cognitive decline.

Objectives Excessive visceral fat is associated with greater metabolic fluctuation and increased risk for dementia in older adults. The aim of the current study is to directly determine the impact of central adiposity on brain structure at midlife by examining the thickness of the cerebral cortex. Methods High-resolution magnetization-prepared rapid acquisition gradient-echo images were obtained from 103 participants aged 40 to 60 years (mean [standard deviation] = 49.63 [6.47] years) on a 3-T Siemens Skyra scanner. Visceral fat was measured using dual-energy x-ray absorptiometry. Results Individuals with higher visceral fat mass and volume had significantly thicker cortex in the right posterior cingulate gyrus (β = 0.29 [p = .019] and β = 0.31 [p = .011], respectively), controlling for age, systolic blood pressure, total cholesterol level, and blood glucose level. Conclusions Visceral fat was significantly associated with thicker cortex in the posterior cingulate gyrus. Although future studies are necessary, these results indicate that central adiposity is associated with significant metabolic changes that impinge upon the central nervous system in middle age.

Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health to measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, gender, years of education, and mental status. Arterial stiffness was characterized via β-stiffness index and carotid-femoral pulse-wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

Objective: The purpose of this article is to examine how psychosocial distress and HSV-1 might interact to foster early cognitive vulnerability in otherwise healthy middle-aged adults. Several environmental risk factors, including mental stress and chronic viral infections, can increase cognitive vulnerability and lead to cognitive decline. Considering the anticipated dramatic increase in the number of older adults with dementia in the next 40 years and the current lack of dementia cures, it is imperative that we explore any modifiable risk factors for brain vulnerability that may facilitate the development of interventions to prevent or delay the onset of severe cognitive impairment. Methods: A total of 113 participants, 63 female and 50 male, were recruited for this study. 15 cc of blood was obtained by venipuncture from consenting volunteers and screened with the ELISA tests to assess seropositivity for HSV-1 IgG antibodies. Cognitive vulnerability was operationalized as lower cognitive function across any of the following 3 domains: global, memory, executive function. The Beck Depression Inventory (BDI-II) was used to assess depressive symptoms. Results: After controlling for age, gender, and education, there was a significant main effect for HSV-1, F(1,106)=7.908, p=0.01, but not for depressive symptoms, on global cognition. However, this main effect was qualified by a statistically significant interaction between the factors, F(1,106)=5.046, p=0.03. No significant main effects or interactions were found for memory or executive function. Conclusion: The results of this study show that even subclinical depressive symptoms can exacerbate the negative effect of HSV-1 infection on global cognitive function. We found that seropositive individuals reporting at least some depressive symptoms exhibited worse performance on a test of intelligence than seropositive individuals without depressive symptoms.

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity-related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.

The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40-62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization, and tract-based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337-3344, 2017. © 2017 Wiley Periodicals, Inc.

Objective To examine clinical, cognitive, and psychological predictors of Quality of Life (QOL) among Hispanics and non-Hispanics with epilepsy. Participants and Method Data was collected from 90 patients (52 Hispanic; H, 38 Non-Hispanic; NH) diagnosed with epilepsy and referred for neuropsychological evaluation that included measures of depression (BDI-II), anxiety (BAI), and QOL using the Personal Impact of Epilepsy Scale (PIES). We conducted multiple linear regression models with patient’s full-scale IQ, age of seizure onset, duration of seizure disorder, and anxiety and depression symptom severity entered as predictors, with the PIES as outcome measure. Results There were no significant differences between H and NH on any demographic or clinical variable except for longer duration of seizure disorder (t = 2.20, p = 0.03) in H. For the complete sample, higher FSIQ predicted better QOL in relation to the perceived disabling effects of seizures (β = .28, p =.02), higher BDI-II scores predicted more negative medication side effects and greater mood related disruption in QOL (β = -2.27, p =.03; β = -3.82, p =.00), and higher BAI scores were the best predictor for worse overall QOL (β = -.29, p = .05). When the sample was divided according to ethnic background, longer seizure duration was associated with the adverse effects of less medication in the H group (β = .32, p =.04), with all other findings being identical to those of the complete sample. When results for NH patients were analyzed, none of the intellectual, psychological and clinical variables were significantly associated with any of the QOL scales; however, the relationship between the BAI and comorbid mood dysfunction approached significance (β = -1.45, p = .059). Conclusions Our data indicates that overall QOL was primarily predicted by the severity of anxiety symptoms, but not influenced by overall intelligence, symptoms of depression, and clinical seizure variables.

Background Excessive adipose tissue, particularly with a centralized distribution, propagates hormonal and metabolic disturbance. The detrimental effects of adiposity may extend beyond the periphery and target the central nervous system, increasing vulnerability to cognitive decline. The aim of current study was to determine how central adiposity impacts the brain at midlife by examining the blood oxygen level-dependent (BOLD) response to a challenging cognitive task. Methods Seventy-three adults, aged 40-60 years, completed a 2-Back verbal working memory task during functional magnetic resonance imaging (fMRI). Central adiposity was assessed with waist circumference. The association between waist circumference and task-related activation in a priori regions of interest was modeled using bootstrapping regression models corrected for multiple-comparisons. Results Larger waist circumference was associated with diminished working-memory-related BOLD response in the right superior frontal gyrus (β=-0.008, p=0.001, 95% CI: -0.012 - -0.004) and left middle frontal gyrus (β=-0.009, p=0.002, 95% CI: -0.015 - -0.003), statistically adjusting for age, sex, systolic blood pressure, and total cholesterol. Reduced task-related activation in the right superior frontal gyrus (r=-0.369, p=0.002) and left middle frontal gyrus (r=-0.266, p=0.025) were related to slower reaction time on the task, controlling for age and education. Conclusions Larger waist circumference predicted alterations in the BOLD response that coupled with decrements in task performance. While future studies are necessary, the results suggest that similar to its role in the periphery, central adiposity may be a robust predictor of metabolic and hormonal alterations that impinge upon central nervous system functioning.

The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40-62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization, and tract-based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337-3344, 2017. © 2017 Wiley Periodicals, Inc.

BACKGROUND: Excessive adipose tissue, particularly with a central distribution, consists of visceral fat, which is metabolically active and could impinge upon central nervous system functioning. The aim of the current study was to examine levels of visceral adiposity in relation to key cerebral metabolite ratios localized in the occipitoparietal grey matter. METHODS: Seventy-three adults, aged between 40–60 years, underwent structural magnetic resonance imaging and single voxel (1)H Magnetic Resonance Spectroscopy ((1)H MRS). Visceral fat was assessed using Dual Energy X Ray Absorptiometry (DXA). RESULTS: Individuals with higher visceral fat mass and volume had significantly lower ratios of N-acetyl-aspartate to total creatine (phosphocreatine+creatine, PCr+Cr) (NAA/PCr+Cr) (β = −0.29, p=0.03, β = −0.28, p=0.04). They also had significantly higher ratios of myo-inositol to total creatine (mI/PCr+Cr ) (β = 0.36, p=0.01, β = 0.36, p=0.01). Visceral fat mass and volume were not significantly related to ratios of glutamate to total creatine (Glu/PCr+Cr). CONCLUSIONS: Visceral fat was associated with lower NAA/PCr+Cr ratio and higher mI/PCr+Cr ratios. While future studies are necessary, these results indicate central adiposity is associated with metabolic changes that could impinge upon the central nervous system in middle age.

Background: Providing optimal treatment is pivotal to improved health and justice outcomes for patients with dual diagnosis. Unfortunately, the available evidence suggests that these patients may be unduly prejudiced during hospitalisation due to perceptions that their requests for pro re nata (PRN) medication is ‘drug-seeking’, reflecting persistent dependence or tendencies toward abuse of licit and illicit substances. Aims: To examine psychiatric nurses' responses to patients requests for PRN medication, to examine whether these requests are interpreted as ‘drug-seeking’, and to characterise patients described as such. Method: Case files and medication charts of patients diagnosed with schizophrenia admitted to a secure psychiatric service were reviewed to determine (a) their history of drug use, (b) the frequency with which they requested PRN medication, (c) how often staff administered PRN medication following request, and (d) how often patients were labelled ‘drug seeking’. Results: Patients with a h...

Engagement in regular aerobic exercise is associated with cognitive benefits, but information on the mechanisms governing these changes in humans is limited. The goal of the current study was to compare neurometabolite concentrations relating to cellular metabolism, structure, and viability in endurance-trained and sedentary middle-aged adults. Twenty-eight endurance-trained and 27 sedentary adults, aged 40-65 years, underwent general health assessment, cardiorespiratory fitness measurement, neuropsychological testing, and proton magnetic resonance spectroscopy ((1)H MRS). (1)H MRS was used to examine N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in frontal and occipitoparietal grey matter. Group differences in concentrations of NAA, Cho, mI, and Glu, calculated as ratios over Cr, were explored using ANOVA. There were no significant differences in global cognitive function, memory, and executive function performance between the groups. In comparison to sedentary adults, the endurance-trained group displayed significantly higher NAA/Cr in the frontal grey matter (F(1, 53) = 5.367, p = 0.024) and higher Cho/Cr in the occipitoparietal grey matter (F(1, 53) = 5.138, p = 0.028). Within our middle-aged sample, endurance-trained adults demonstrated higher levels of NAA/Cr in the frontal grey matter and higher Cho/Cr in the occipitoparietal grey matter. Higher levels of NAA may indicate greater neuronal integrity and higher cerebral metabolic efficiency in association with cardiorespiratory fitness, whereas increased Cho may represent increased phospholipid levels secondary to neural plasticity.

While studying packs of the eastern timber wolf in Algonquin Provincial Park in Ontario, DNA profiles at 8 microsatellite loci and the mitochondrial control region were found to be similar to those of the red wolf, C. rufus. Based on this it was suggested that both the red wolf and the eastern timber wolf have a common origin, evolving in North America, with the coyote diverging from them 150,000-300,000 years ago and with neither having any recent connection with the gray wolf that evolved in Eurasia. It was further proposed, that the eastern timber wolf retain its original species designation of C. lycaon instead of the present status of a subspecies of the gray wolf. Four "types" or "races" of wolves have been previously described in Ontario. Using DNA profiles, assignment tests identified four groups, which were typified by animals in Algonquin Provincial Park, Pukaskwa National Park, Frontenac Axis and those north of Lake Superior. The tests indicate that Frontenac animals are hybrids between the western coyote and C. lycaon and represent the eastern coyote. Pukaskwa maintains a small wolf population, which is genetically closer to the gray wolves of the Northwest Territories than the surrounding C. lycaon. These may represent an isolated remnant population of the original "Ontario type" (C. lupus). Animals north of Lake Superior were identified as C. lycaon, but represent products of hybridization between C. lycaon and C. lupus. Currently within Ontario, Algonquin Park contains the largest protected area of the eastern timber wolf. DNA profiles, including Y-linked microsatellite loci were used to establish maternity, paternity and kin relationships for 102 animals from 24 packs over a 12-year period. A complex pack structure was identified. A pack is not composed simply of an unrelated breeding pair and their offspring and subordinates appear to enter pack systems through adoption, pack splitting, dispersal and immigration. Relatively high genetic structuring was found between the Park animals and the "Tweed" wolves to the southeast suggesting introgression of coyote genetic material is not a present concern to the integrity of park animals. Evidence of gene flow with animals to the west, northeast and northwest coupled with the high genetic diversity, suggest that the Park animals are not an island population, but the southern part of a larger metapopulation of C. lycaon. Increased interest in the relationship of the red and eastern wolves led to the investigation of a gene in the major histocompatibility complex. Allelic variation in the exon 2 region of the DLA-DQA1 locus was analysed for gray wolves, red wolves, the eastern timber wolf and the western coyote. Twelve alleles were identified, seven of which were previously characterized in dogs. Non-synonomous nucleotide substitutions was 3.0 times higher than the synonomous changes, indicative of strong positive selection. These data provide baselines for the determination of allele frequencies and their distribution across the geographical range of the four species in North America. The results in this thesis have sparked numerous debates with respect to the protection of the wolves in Algonquin Provincial Park and reintroduction of wolves into Northeastern United States. The data support the idea that the C. lycaon population in Ontario is relatively large, numbering in the thousands rather than the hundreds. Concern for the conservation of wolves in Ontario should be directed at the declining numbers of gray wolves present in Ontario. Thesis Master of Science (MSc)