Hepatitis B Vaccination Response in Hemodialysis Patients: The Impact of Dialysis Shift.

BACKGROUND/AIMS: Hepatitis B (HB) vaccination in hemodialysis patients is important as they are at a higher risk of contracting HB. However, hemodialysis patients have a lower HB seroconversion rate than their healthy counterparts. As better sleep has been associated with better seroconversion in healthy populations and early hemodialysis start has been linked to significant sleep-wake disturbances in hemodialysis patients, we examined if hemodialysis treatment start time is associated with HB vaccination response. METHODS: Demographics, standard-of-care clinical, laboratory, and treatment parameters, dialysis shift data, HB antigen status, HB vaccination status, and HB titers were collected from hemodialysis patients in Fresenius clinics from January 2010 to December 2015. Patients in our analysis received 90% of dialysis treatments either before or after 8:30 a.m., were negative for HB antigen, and received a complete series of HB vaccination (Engerix B® or Recombivax HB™). Univariate and multivariate regression models examined whether dialysis start time is a predictor of HB vaccination response. RESULTS: Patients were 65 years old, 57% male, and had a HD vintage of 10 months. Patients whose dialysis treatments started before 8:30 a.m. were more likely to be younger, male, and have a greater dialysis vintage. Patients receiving Engerix B® and starting dialysis before 8:30 a.m. had a significantly higher seroconversion rate compared to patients who started dialysis after 8:30 a.m. Early dialysis start was a significant predictor of seroconversion in univariate and multivariate regression including male gender, but not in multivariate regression including age, neutrophil-to-lymphocyte ratio, and vintage. CONCLUSION: While better sleep following vaccination is associated with seroconversion in the general population, this is not the case in hemodialysis patients after multivariate adjustment. In the context of end-stage kidney disease, early dialysis start is not a significant predictor of HB vaccination response. The association between objectively measured postvaccination sleep duration and seroconversion rate should be investigated.

Relationships between Neighborhood Walkability and Objectively Measured Physical Activity Levels in Hemodialysis Patients.

BACKGROUND/AIMS: Neighborhood walkability is associated with indicators of health in the general population. We explored the association between neighborhood walkability and daily steps in hemodialysis (HD) patients. METHODS: We measured daily steps over 5 weeks using Fitbit Flex (Fitbit, San Francisco, CA, USA) and retrieved Walk Score® (WS) data by patient's home ZIP code (www.walkscore.com; 0 = poorest walkability; 100 = greatest walkability). RESULTS: HD patients took a mean of 6,393 ± 3,550 steps/day (n = 46). Median WS of the neighborhood where they resided was 28. Patients in an above-median WS (n = 27) neighborhood took significantly more daily steps compared to those (n = 19) in a below-median WS neighborhood (7,514 ± 3,900 vs. 4,800 ± 2,228 steps/day; p < 0.001, t test). Daily steps and WS were directly correlated (R = 0.425; p = 0.0032, parametric test; R = 0.359, p = 0.0143, non-parametric test). CONCLUSION: This is the first study conducted among HD patients to indicate a direct relationship between neighborhood walkability and the actual steps taken. These results should be considered when designing initiatives to increase and improvise exercise routines in HD populations.

Erythrocyte Sodium Sensitivity and Eryptosis in Chronic Hemodialysis Patients.

BACKGROUND/AIMS: In hemodialysis (HD) patients the endothelial and erythrocyte glycocalyx is impaired which in turn correlates with elevated erythrocyte sodium sensitivity (ESS). Additionally, apoptotic erythrocyte death (eryptosis), characterized by phosphatidylserine (PS) exposure on the cell surface, is increased in this population. We aimed to explore the relationship of ESS and eryptosis. METHODS: Blood samples were collected from 11 healthy controls and 20 chronic HD patients before and after midweek HD. ESS was quantified by the salt blood test. PS-exposure, intracellular reactive oxygen species (ROS) of erythrocytes and reticulocytes were assessed by flow cytometry. RESULTS: Compared to controls ESS was significantly higher in HD patients preHD and did not change during treatment. The percentage of eryptotic cells did not differ between controls and patients preHD. However, eryptosis decreased during HD. ESS and eryptosis were uncorrelated, while eryptosis was positively correlated with intracellular ROS and percent reticulocytes. CONCLUSIONS: Higher ESS levels in HD patients indicate a pathologic glycocalyx. ESS and eryptosis were not correlated. The decreased eryptosis postHD may possibly be related to dialytic uremic toxin removal, but is likely multifactorial. The relationship between eryptosis and intracellular ROS warrants further research.

Physical Activity and Sleep Patterns in Hemodialysis Patients in a Suburban Environment.

BACKGROUND/AIMS: Hemodialysis (HD) patients are less active than their healthy counterparts. They are often plagued with sleep disorders that affect the quality of their sleep. Our aim was to objectively quantify activity and sleep quality among HD patients in a suburban HD population. METHODS: Activity and sleep parameters were measured using a commercially available activity tracker in 29 HD patients from Baton Rouge, LA, USA. Patients in the feedback group received their activity and sleep data at each dialysis treatment. In addition, questionnaires were administered at the beginning and end of the study period. Patients were stratified based on activity levels and sleep quality. RESULTS: Patients walked an average of 5,281 steps/day and slept 370.5 min/night. Informing patients about their daily number of steps taken, did not increase activity. Only 3% of the population followed were active, defined as walking more than 10,000 steps per day. Patients walked significantly less on dialysis days compared to the other days of the week. Many of the patients experienced poor sleep quality, with patients in the first shift experiencing the greatest disturbance to their sleep/wake cycle. CONCLUSION: Patients in a suburban environment walked much less than those in a previously studied urban population. They rarely met the recommended goal of 10,000 steps/day, even on non-dialysis days. Interventions to increase physical activity may target any day of the week, particularly HD days. Prospective, long-term studies are needed to evaluate the use of activity trackers in dialysis patients and their impact on physical activity.

Correlation between Inflammatory Biomarkers and Red Blood Cell Life Span in Chronic Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: The pathogenesis of anemia in hemodialysis (HD) patients is dependent on multiple factors, with decreased red blood cell life span (RBCLS) being a significant contributor. Although the impact of reduced RBCLS on anemia is recognized, it is still a subject that is not well researched. The objective of this study was to investigate the relationship between RBCLS and inflammatory biomarkers in chronic HD patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: RBCLS was calculated from alveolar carbon monoxide concentrations measured by gas chromatography. Interleukins (IL) IL-6, IL-18, IL-10, and high sensitivity C-reactive protein were measured using bead-based multiplex assay. Measurements were carried out at baseline and during follow-up. The associations between RBCLS and inflammatory biomarkers were evaluated using linear mixed effects models. RESULTS: RBCLS measurements were available for 54 HD patients. Their average age was 58.5 ± 14.4 years, 68.5% were males, 48.1% were diabetics, and the HD vintage was 51 ± 48 months. In 4 patients, RBCLS was measured once, while in 50 patients, up to 5 repeated RBCLS measurements were available. RBCLS was 73.2 ± 17.8 days (range 37.7-115.8 days). No association was found between RBCLS and any of the inflammatory biomarkers. Of note, RBCLS was positively correlated with levels of uric acid (p = 0.02) and blood urea nitrogen (BUN; p = 0.01), respectively. CONCLUSION: Our study suggests that inflammation pathways reported by these biomarkers only have a limited role in causing premature RBC death. The positive correlation with uric acid and BUN warrants further studies.

Quantifying Physical Activity Levels and Sleep in Hemodialysis Patients Using a Commercially Available Activity Tracker.

BACKGROUND/AIMS: Hemodialysis (HD) patients are less active than their healthy counterparts and frequently experience poor sleep. Our aims were to objectively quantify activity and sleep quality in HD patients of an urban population and to determine the effect of providing feedback on activity. METHODS: Activity parameters and sleep parameters were collected by a commercially available activity tracker in 29 chronic HD patients. Patients in the feedback group were provided with their activity and sleep data during each HD treatment. Questionnaires were administered at the beginning and at the end of the study. RESULTS: On average, patients walked 8,454 steps/day and slept 349 min/night. Only 28% of the patients were sedentary, defined as walking <5,000 steps/day. Providing feedback did not increase the activity in this urban population. Patients walked significantly less on Sundays compared to other days of the week: 7,024 steps on Sundays vs. 8,633 steps on HD days and 8,732 on non-HD days. It was also found that patients experienced poor sleep quality. HD treatments during shift 1 (6 a.m. to 10 a.m.) interfered with sleep patterns. Most patients reported that physical activity became more important to them after the 5-week period. The tracking device was very well accepted. CONCLUSION: Interventions to increase physical activity on Sundays could improve physical activity levels overall. Prospective studies are necessary to further explore the use of tracking devices to identify patients at risk and to implement targeted interventions.

Reduced retention of Pittsburgh compound B in white matter lesions.

PURPOSE: One of the interesting features of the amyloid tracer Pittsburgh compound B (PiB) is that it generates a signal in the white matter (WM) in both healthy subjects and cognitively impaired individuals. This characteristic gave rise to the possibility that PiB could be used to trace WM pathology. In a group of cognitively healthy elderly we examined PiB retention in normal-appearing WM (NAWM) and WM lesions (WML), one of the most common brain pathologies in aging. METHODS: We segmented WML and NAWM on fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9 ± 10.0, 71 % women). PiB PET images were corrected for partial volume effects and coregistered to FLAIR images and WM masks. WML and NAWM PiB signals were then extracted. RESULTS: PiB retention in WML was lower than in NAWM (p < 0.001, 14.6 % reduction). This was true both for periventricular WML (p < 0.001, 17.8 % reduction) and deep WML (p = 0.001, 7.5 % reduction). CONCLUSION: PiB binding in WM is influenced by the presence of WML, which lower the signal. Our findings add to the growing evidence that PiB can depict WM pathology and should prompt further investigations into PiB binding targets in WM.

Sex-specific associations of serum cortisol with brain biomarkers of Alzheimer's risk.

Emerging evidence implicates chronic psychological stress as a risk factor for Alzheimer's disease (AD). Herein, we examined the relationships between serum cortisol and multimodality brain AD biomarkers in 277 cognitively normal midlife individuals at risk for AD. Overall, higher cortisol was associated with lower total brain volume, lower glucose metabolism (CMRglc) in frontal cortex, and higher ß-amyloid (Aß) load in AD-vulnerable regions; and marginally associated with phosphocreatine to ATP ratios (PCr/ATP) in precuneus and parietal regions. Sex-specific modification effects were noted: in women, cortisol exhibited stronger associations with Aß load and frontal CMRglc, the latter being more pronounced postmenopause. In men, cortisol exhibited stronger associations with gray matter volume and PCr/ATP measures. Higher cortisol was associated with poorer delayed memory in men but not in women. Results were adjusted for age, Apolipoprotein E (APOE) epsilon 4 status, midlife health factors, and hormone therapy use. These results suggest sex-specific neurophysiological responses to stress, and support a role for stress reduction in AD prevention.

Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Introduction: Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. Methods: We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Results: Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. Discussion: These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology.

17ß-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women's health.

Increased fibrillar amyloid-{beta} burden in normal individuals with a family history of late-onset Alzheimer's.

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor among cognitively normal (NL) individuals. This (11)C-Pittsburgh Compound B (PiB)-PET study examines whether NL individuals with LOAD parents show increased fibrillar amyloid-beta (Abeta) deposition, a hallmark of Alzheimer's disease (AD) pathology and whether there are parent-of-origin effects. Forty-two 50- to 80-year-old NL persons were examined with PiB-PET. These individuals included 14 NL subjects with a maternal family history (FH) of LOAD (FHm), 14 NL subjects with a paternal FH (FHp), and 14 NL subjects with a negative family history of any dementia (FH-). Statistical parametric mapping and automated regions-of-interest were used to compare cerebral-to-cerebellar PiB standardized uptake value ratios, reflecting fibrillar Abeta burden, across groups. FH groups did not differ in age, gender, education, and apolipoprotein E (ApoE) status. NL FHm subjects showed higher PiB retention in AD-affected anterior and posterior cingulate cortex (PCC), precuneus, parietal, temporal, occipital, and frontal cortices, right basal ganglia, and thalamus, compared with FH- and FHp subjects. FHp subjects showed increased PiB retention in the PCC and frontal cortex, intermediate between FHm and FH- subjects. Results remained significant after controlling for age, gender, education, and ApoE status. Children of parents with LOAD, particularly those with affected mothers, have increased fibrillar Abeta load in AD-vulnerable regions compared with controls, perhaps accounting for the known increased risk for AD. Present findings may motivate further research on familial transmission and parent-of-origin effects in LOAD.

Systematic review of 31P-magnetic resonance spectroscopy studies of brain high energy phosphates and membrane phospholipids in aging and Alzheimer's disease.

Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial dysfunction, cerebral energy dysmetabolism and oxidative damage increase with age, and are early event in AD pathophysiology and may precede amyloid beta (Aß) plaques. In vivo probes of mitochondrial function and energy metabolism are therefore crucial to characterize the bioenergetic abnormalities underlying AD risk, and their relationship to pathophysiology and cognition. A majority of the research conducted in humans have used 18F-fluoro-deoxygluose (FDG) PET to image cerebral glucose metabolism (CMRglc), but key information regarding oxidative phosphorylation (OXPHOS), the process which generates 90% of the energy for the brain, cannot be assessed with this method. Thus, there is a crucial need for imaging tools to measure mitochondrial processes and OXPHOS in vivo in the human brain. 31Phosphorus-magnetic resonance spectroscopy (31P-MRS) is a non-invasive method which allows for the measurement of OXPHOS-related high-energy phosphates (HEP), including phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi), in addition to potential of hydrogen (pH), as well as components of phospholipid metabolism, such as phosphomonoesters (PMEs) and phosphodiesters (PDEs). Herein, we provide a systematic review of the existing literature utilizing the 31P-MRS methodology during the normal aging process and in patients with mild cognitive impairment (MCI) and AD, with an additional focus on individuals at risk for AD. We discuss the strengths and limitations of the technique, in addition to considering future directions toward validating the use of 31P-MRS measures as biomarkers for the early detection of AD.

Effects of sex and APOE ε4 genotype on brain mitochondrial high-energy phosphates in midlife individuals at risk for Alzheimer's disease: A 31Phosphorus MR spectroscopy study.

Age, female sex, and APOE epsilon 4 (APOE4) genotype are the three greatest risk factors for late-onset Alzheimer's disease (AD). The convergence of these risks creates a hypometabolic AD-risk profile unique to women, which may help explain their higher lifetime risk of AD. Less is known about APOE4 effects in men, although APOE4 positive men also experience an increased AD risk. This study uses 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) to examine effects of sex and APOE4 status on brain high-energy phosphates [adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi)] and membrane phospholipids [phosphomonoesters (PME), phosphodiesters (PDE)] in 209 cognitively normal individuals at risk for AD, ages 40-65, 80% female, 46% APOE4 carriers (APOE4+). Women exhibited lower PCr/ATP and PCr/Pi levels than men in AD-vulnerable regions, including frontal, posterior cingulate, lateral and medial temporal cortex (multi-variable adjusted p≤0.037). The APOE4+ group exhibited lower PCr/ATP and PCr/Pi in frontal regions as compared to non-carriers (APOE4-) (multi-variable adjusted p≤0.005). Sex by APOE4 status interactions were observed in frontal regions (multi-variable adjusted p≤0.046), where both female groups and APOE4+ men exhibited lower PCr/ATP and PCr/Pi than APOE4- men. Among men, APOE4 homozygotes exhibited lower frontal PCr/ATP than heterozygotes and non-carriers. There were no significant effects of sex or APOE4 status on Pi/ATP and PME/PDE measures. Among midlife individuals at risk for AD, women exhibit lower PCr/ATP (e.g. higher ATP utilization) and lower PCr/Pi (e.g. higher energy demand) than age-controlled men, independent of APOE4 status. However, a double dose of APOE4 allele shifted men's brains to a similar metabolic range as women's brains. Examination of brain metabolic heterogeneity can support identification of AD-specific pathways within at-risk subgroups, further advancing both preventive and precision medicine for AD.

Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.

Introduction: Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk. Methods: Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies. Results: Randomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16-1.64, p < 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20-2.25, p = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92-1.54, p = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64-0.95, p = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70-0.94, p = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77-0.95, p = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775-1.069, p = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513-0.915, p = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474-1.266, p = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979-1.789, p = 0.069; ET: RR = 1.066, 95% C.I. 0.996-1.140, p = 0.066]. Discussion: These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.

Elevated gonadotropin levels are associated with increased biomarker risk of Alzheimer's disease in midlife women.

Introduction: In preclinical studies, menopausal elevations in pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), trigger Alzheimer's disease (AD) pathology and synaptic loss in female animals. Herein, we took a translational approach to test whether gonadotropin elevations are linked to AD pathophysiology in women. Methods: We examined 191 women ages 40-65 years, carrying risk factors for late-onset AD, including 45 premenopausal, 67 perimenopausal, and 79 postmenopausal participants with clinical, laboratory, cognitive exams, and volumetric MRI scans. Half of the cohort completed 11C-Pittsburgh Compound B (PiB) amyloid-ß (Aß) PET scans. Associations between serum FSH, LH and biomarkers were examined using voxel-based analysis, overall and stratified by menopause status. Associations with region-of-interest (ROI) hippocampal volume, plasma estradiol levels, APOE-4 status, and cognition were assessed in sensitivity analyses. Results: FSH levels were positively associated with Aß load in frontal cortex (multivariable adjusted P≤0.05, corrected for family wise type error, FWE), an effect that was driven by the postmenopausal group (multivariable adjusted PFWE ≤ 0.044). LH levels were also associated with Aß load in frontal cortex, which did not survive multivariable adjustment. FSH and LH were negatively associated with gray matter volume (GMV) in frontal cortex, overall and in each menopausal group (multivariable adjusted PFWE ≤ 0.040), and FSH was marginally associated with ROI hippocampal volume (multivariable adjusted P = 0.058). Associations were independent of age, clinical confounders, menopause type, hormone therapy status, history of depression, APOE-4 status, and regional effects of estradiol. There were no significant associations with cognitive scores. Discussion: Increasing serum gonadotropin levels, especially FSH, are associated with higher Aß load and lower GMV in some AD-vulnerable regions of midlife women at risk for AD. These findings are consistent with preclinical work and provide exploratory hormonal targets for precision medicine strategies for AD risk reduction.

In vivo Brain Estrogen Receptor Expression By Neuroendocrine Aging And Relationships With Gray Matter Volume, Bio-Energetics, and Clinical Symptomatology.

17ß-estradiol,the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo multi-modality neuroimaging study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age and plasma estradiol levels, and were highly consistent, correctly classifying all women as being post-menopausal or not. Higher ER density was generally associated with lower gray matter volume and blood flow, and with higher mitochondria ATP production, possibly reflecting compensatory mechanisms. Additionally, ER density predicted changes in thermoregulation, mood, cognition, and libido. Our data provide evidence that ER density impacts brainstructure, perfusion and energy production during female endocrine aging, with clinical implications for women's health.

Robust and conventional neuropsychological norms: diagnosis and prediction of age-related cognitive decline.

The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up. Conventional and Robust norms were tested in an independent cohort of longitudinally studied healthy (n=223), MCI (n=136), and Alzheimer's disease (AD, n=162) participants; 84 healthy participants declined to MCI or AD (NL-->DEC), and 44 MCI declined to AD (MCI-->AD). Compared to Conventional norms, baseline Robust norms correctly identified a higher proportion of NL-->DEC with impairment in delayed memory and attention-language domains. Both norms predicted decline from MCI-->AD. Change norms for delayed memory and attention-language significantly incremented baseline classification accuracies. These findings indicate that Robust norms improve identification of healthy individuals who will decline and may be useful for selecting at-risk participants for research studies and early interventions.

Estimation of arterio-venous access blood flow in hemodialysis patients using video image processing technique.

Assessment of arterio-venous fistula (AVF) blood flow (ABF) is vital in hemodialysis (HD) patients. Currently, no non-invasive and contact-free technique is available to accurately measure ABF in routine clinical practice. In this study, we developed a novel approach using video image processing (VIP) to measure the change in optic flow in the skin. We the tested the hypothesis that the change in optical flow, expressed as the change in pixels between consecutive frames, is related to ABF. We recorded AVF videos in 40 HD patients using a digital camera and processed them by VIP technique. We then compared the actual ABF as measured by routine online clearance (ABFOLC) and the amplitude (AMP) of optical flow. Technical and procedural errors rendered VIP invalid in 13 patients. In the remaining 27 patients the optical flow AMP was significantly lower in patients with low (<;900 ml/min) ABFOLC compared to patients with normal (≥900 ml/min) ABFOLC (AMP 3.4±1*103 vs 5.2±1.4 *103 [pixels], p<;0.01). In these 27 patients AMP correlated with ABFOLC (R2=0.71, p<;0.0001). While more extensive research is necessary, these preliminary results indicate the potential usefulness of the VIP technique to identify low ABF.

Effects of vascular risk factors, statins, and antihypertensive drugs on PiB deposition in cognitively normal subjects.

INTRODUCTION: Hypertension, hypercholesterolemia, and obesity increase the risk of dementia. Although their detection is commonly followed by an introduction of treatment, little is known about how medications frequently used to treat vascular risk affect amyloid deposition. METHODS: A cross-sectional study of 156 subjects who underwent positron emission tomography with PiB. Using linear regression, we tested whether blood pressure, cholesterol, overweight/obese status, angiotensin receptor blockers (ARBs), beta-blockers, diuretics, angiotensin converting enzyme inhibitors, and statins predicted amyloid deposition. RESULTS: The use of ARBs (ß = -.15, P = .044) and diuretics (ß = -.20, P = .006) predicted less amyloid accumulation; older age (ß = .29, P < .001) and statins (ß = .23, P = .004) were related to greater amyloid deposition. Overweight and/or obese women had more cortical amyloid than their peers. DISCUSSION: Prospective studies should confirm effects of drugs and increased body weight on amyloid accumulation and establish whether they translate into measurable clinical outcomes. Women may be more susceptible to harmful effects of obesity.

Periodontal disease associates with higher brain amyloid load in normal elderly.

The accumulation of amyloid-ß (Aß) plaques is a central feature of Alzheimer's disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory and/or infectious conditions in humans can promote Aß brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Thirty-eight cognitively normal, healthy, and community-residing elderly (mean age, 61 and 68% female) were examined in an Alzheimer's Disease Research Center and a University-Based Dental School. Linear regression models (adjusted for age, apolipoprotein E, and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aß load using (11)C-Pittsburgh compound B (PIB) positron emission tomography imaging. After adjusting for confounders, clinical attachment loss (≥3 mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased PIB uptake in Aß vulnerable brain regions (p = 0.002). We show for the first time in humans an association between periodontal disease and brain Aß load. These data are consistent with the previous animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aß accumulations.