Sex-Driven Differences in the Effectiveness of Individualized Clinical Management of Alzheimer's Disease Risk.

BACKGROUND: The Comparative Effectiveness Dementia and Alzheimer's Registry (CEDAR) trial demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of Alzheimer's disease (AD). As biological sex is a significant risk factor for AD, it is essential to explore the differential effectiveness of targeted clinical interventions in women vs. men. METHODS: Patients were recruited from an Alzheimer's Prevention Clinic. Subjects with normal cognition, subjective cognitive decline, or asymptomatic preclinical AD were classified as "Prevention". Subjects with mild cognitive impairment due to AD or mild AD were classified as "Early Treatment." The primary outcome was the change from baseline to 18-months on the modified-Alzheimer's Prevention Cognitive Composite. Secondary outcomes included a cognitive aging composite, AD and cardiovascular (CV) risk scales, and serum biomarkers. Subjects who adhered to > 60% of recommendations in the CEDAR trial were included in this a priori sub-group analysis to examine whether individualized intervention effects were modified by sex (n=80). RESULTS: In the Prevention group, both women (p=0.0205) and men (p=0.0044) demonstrated improvements in cognition with no sex differences (p=0.5244). In the Early Treatment group, there were also no significant sex differences in cognition (p=0.3299). In the Prevention group, women demonstrated greater improvements in the Multi-Ethnic Study of Atherosclerosis risk score (MESA-RS) than men (difference=1.5, p=0.0013). Women in the Early Treatment group demonstrated greater improvements in CV Risk Factors, Aging and Incidence of Dementia (CAIDE) risk score (difference=2.3, p=0.0067), and the MESA-RS (difference=4.1, p<0.001). CONCLUSIONS: Individualized multi-domain interventions are equally effective at improving cognition in women and men. However, personally-tailored interventions led to greater improvements in calculated AD and CV risk, and CV blood biomarkers, in women compared to men. Future study in larger cohorts is necessary to further define sex differences in AD risk reduction in clinical practice.

Feasibility of Using a Wearable Biosensor Device in Patients at Risk for Alzheimer's Disease Dementia.

BACKGROUND: Alzheimer's disease (AD) is the most common and most costly chronic neurodegenerative disease globally. AD develops over an extended period prior to cognitive symptoms, leaving a "window of opportunity" for targeted risk-reduction interventions. Further, this pre-dementia phase includes early physiological changes in sleep and autonomic regulation, for which wearable biosensor devices may offer a convenient and cost-effective method to assess AD-risk. METHODS: Patients with a family history of AD and no or minimal cognitive complaints were recruited from the Alzheimer's Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian. Of the 40 consecutive patients screened, 34 (85%) agreed to wear a wearable biosensor device (WHOOP). One subject (2.5%) lost the device prior to data collection. Of the remaining subjects, 24 were classified as normal cognition and were asymptomatic, 6 were classified as subjective cognitive decline, and 3 were amyloid-positive (one with pre-clinical AD, one with pre-clinical Lewy-Body Dementia, and one with mild cognitive impairment due to AD). Sleep-cycle, autonomic (heart rate variability [HRV]) and activity measures were collected via WHOOP. Blood biomarkers and neuropsychological testing sensitive to cognitive changes in pre-clinical AD were obtained. Participants completed surveys assessing their sleep-patterns, exercise habits, and attitudes towards WHOOP. The goal of this prospective observational study was to determine the feasibility of using a wrist-worn biosensor device in patients at-risk for AD dementia. Unsupervised machine learning was performed to first separate participants into distinct phenotypic groups using the multivariate biometric data. Additional statistical analyses were conducted to examine correlations between individual biometric measures and cognitive performance. RESULTS: 27 (81.8%) participants completed the follow-up surveys. Twenty-four participants (88.9%) were satisfied with WHOOP after six months, and twenty-three (85.2%) wanted to continue wearing WHOOP. K-means clustering separated participants into two groups. Group 1 was older, had lower HRV, and spent more time in slow-wave sleep (SWS) than Group 2. Group 1 performed better on two cognitive tests assessing executive function: Flanker Inhibitory Attention/Control (FIAC) (p=.031), and Dimensional Change Card Sort (DCCS) (p=.061). In Group 1, DCCS was correlated with SWS (ρ=.68, p=0.024) and HRV (ρ=.6, p=0.019). In Group 2, DCCS was correlated with HRV (ρ=.55, p=0.018). There were no significant differences in blood biomarkers between the two groups. CONCLUSIONS: Wearable biosensor devices may be a feasible tool to assess AD-related physiological changes. Longitudinal collection of sleep and HRV data may potentially be a non-invasive method for monitoring cognitive changes related to pre-clinical AD. Further study is warranted in larger populations.

Standardization of needlestick injury and evaluation of a novel virus-inhibiting protective glove.

Rubber surgical gloves worn as a barrier to prevent contamination from body fluids offer relative protection against contamination through direct percutaneous injuries involving needles, scalpel blades or bone fragments. To determine the main experimental parameters influencing the volume of blood transmitted by a hollow-bore needle (worst case scenario) during an accidental puncture, we designed an automatic puncture apparatus. Herpes simplex type 1 virus (HSV1), a model for enveloped viruses, was used as a 'marker' in an in-vitro gelatine model. Of the experimental parameters studied, the most critical influences were found to be needle diameter and puncture depth, whereas puncture speed, puncture angle and glove-stretching feature appeared to be less influential. A single glove reduced the volume of blood transferred by 52% compared with no glove, but double gloving offered no additional protection against hollow-bore needle punctures. Using 'standardized' puncture conditions, the virus-inhibiting surgical glove G-VIR elicited an 81% reduction in the amount of HSV1 transmitted as compared with single or double latex glove systems.

Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.

OBJECTIVES: To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic medical center. PARTICIPANTS: Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. INTERVENTION: Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. MEASUREMENTS: Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). RESULTS: At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. CONCLUSION: Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

Cognitive impairment in HIV infection.

HIV-infected subjects at various stages of illness but without opportunistic cerebral disease were evaluated using a comprehensive, cognitively-based neuropsychological protocol and measures of levels of depression and anxiety. The data indicated a prominent attentional disorder among impaired subjects; however, language, visual-spatial and memory functioning were not deficient. There was also evidence suggesting executive function deficit. Depression contributed a small additional component in differentiating the groups. These findings help to specify the nature of the cognitive disturbance associated with HIV encephalopathy and are consistent with the pathological effects of primary infection of the brain by HIV. In addition, they provide a specific basis for ameliorative treatment with psychostimulant medication.

Angioedema following the intravenous administration of metoprolol.

A 72-year-old woman was admitted to the hospital with "flash" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.

'What's his name?' A comparison of elderly participants' and undergraduate students' misnamings.

This study examined the effects of age on the types of errors produced when recalling names of faces. The types of errors included confusions (errors within the target set), intrusions (errors outside the target set), errors phonologically similar to the target, errors not phonologically similar to the target, and errors containing the same number of syllables as the target name. Participants included 49 elderly adults (57-85 years) and 48 undergraduate students (18-44 years). Age group had a significant effect on the number of name errors produced (n=681 for elderly and n=422 for undergraduates). Elderly participants produced more confusions than their younger counterparts; however, younger participants produced significantly more intrusions. The age groups also differed in their production of error names that were phonologically similar to the target name. The elderly participants produced more errors that were not phonologically similar to the target than the young adults. The results are discussed with regard to theories of name-face association and tip-of-the-tongue phenomena.

Peripheral arterial disease. When to consider percutaneous revascularization.

Currently, percutaneous revascularization techniques are recommended for peripheral arterial disease only when limiting or disabling symptoms are present. However, the cost of these procedures is less than that of surgery and the risk is much lower. Additional prospective, randomized studies are needed for better definition of the role of percutaneous techniques in clinical practice. In the future, as techniques evolve and outcomes become better defined, this role may be expanded.

The influence of learning style and cognitive ability on recall of names and faces in an older population.

The present study examined whether, for older adults, a verbal or imagery cognitive style is associated with recall of names and faces learned in an experimental condition. Cognitive abilities that are represented in current models of face recognition and name recall were also examined. Those abilities included picture naming, verbal fluency (i.e., naming items within a given category), vocabulary comprehension, visual memory, and the learning of unassociated word pairs. Fifty older adults attempted to learn first and last names of 20 student actors and actresses pictured on videotapes (40 names total). On average, participants learned the most first names, followed by last names, and the fewest full names. The greater the number of responses on a questionnaire associated with an imagery cognitive style, the more the names of faces were correctly identified by participants. There was no significant relationship between a verbal cognitive style and the number of names and faces recalled. As for cognitive abilities, all of the abilities measured--with the exception of vocabulary comprehension--were significantly associated with the number of names and faces learned. A regression analysis indicated that the best predictor of successful name-face learning was the participants' ability to learn and recall 5 unrelated word pairs. When that cognitive measure was deleted from the regression analysis, delayed visual memory and verbal fluency were the next best predictors of the older adults' ability to learn names and faces.

Emotional stimulation, defensive orientation, and hemispheric activation.

Lateral eye movements (LEM) were measured for 32 right-handed subjects while responding to questions rated for verbal and visual-spatial cognitive content and for varying levels of emotionally stimulating content. The results indicated that eye movements were distributed to the right and left in response to verbal and spatial items, respectively, and that emotional content enhanced leftward responding. In addition, the defensive style of subjects, as measured by a defense mechanism inventory, interacted with the cognitive and affective dimensions of questions and was a determinant of LEM.

Implicit memory in posttraumatic stress disorder with amnesia for the traumatic event.

This report documents a case of posttraumatic stress disorder (PTSD) following psychological trauma with cerebral insult and amnesia for the traumatic event. The case history demonstrates the role of implicit memory in PTSD and indicates that the mechanisms of psychopathology are one-trial sensitization and conditioned emotional responses.

Encoding and complex figure recall.

This study investigated the effects of type of encoding strategy (organized and disorganized) and of active versus passive encoding on memory for interrelated spatial material. Delayed recall performance for a complex, nonrepresentational two dimensional figure was measured in 120 normal young adults assigned to one of three groups that varied as to the approach used during the initial construction of the figure. Those applying self-generated strategies performed best. In addition, recall performances were significantly better for those applying a prescribed, organized strategy as compared with performances of those applying a prescribed, disorganized strategy. These effects were not attributable to differences on measures of IQ or spatial information processing. The findings indicated that, independent of memory ability, both the degree of organization and of active strategizing at encoding are determinants of recall ability for complex spatial information and suggest that these factors have implications for memory processes more generally.

Tower of London procedure: a standard method and developmental data.

The Tower of London procedure (TOL) is being utilized increasingly in clinical and experimental contexts, although there is considerable variation in how it is administered and scored. The procedure detailed here was developed using Shallice's original problems and, along with the Porteus Maze Test (PMT), was administered to 205 elementary school students and 74 young adults. TOL scores increased with age in a linear fashion, and the performance of the sixth, seventh, and eighth grade subjects were not statistically different from the young adults. The TOL was moderately correlated with the PMT suggesting that these procedures share a planning component. These data provide initial developmental standards, and the materials, administration, and scoring procedures documented here provide a standard method for utilization of this instrument.

Emotional distress, coping, and adjustment in human immunodeficiency virus infection and acquired immune deficiency syndrome.

Fifty-seven ambulatory, human immunodeficiency virus (HIV)-infected patients at various stages of disease progression and 17 HIV seronegative controls were examined in a cross-sectional study with self-administered measures of emotional distress, coping, and adjustment to illness. All infected and control subjects were homosexual or bisexual and free of acute medical illness. The findings indicated that both uninfected and infected subjects had enhanced emotional distress in a variety of domains. However, while somatic and cognitive-ruminative complaints were greater in symptomatic subjects relative to controls, depression and anxiety were not. Professed coping strategies were heterogeneous and not particularly related to HIV diagnostic status, with the exception of planful problem solving which was decreased for acquired immune deficiency syndrome subjects. Disruption in several aspects of daily life adjustment was markedly increased in symptomatic subjects. The findings suggest that both HIV seropositive status and perceived risk for infection produce a sustained level of generalized psychological distress. Even in the absence of current medical illness, patients with advanced disease progression are concerned primarily with anticipated medical implications and cognitive effectiveness.

"Kissing balloon" technique in percutaneous transluminal coronary angiography: single-guide catheter, dual-wire, dual-balloon system with single inflation device.

This is a report of a new modification of the "kissing balloon" technique for complex multivessel angioplasty. Based on a series of five consecutive cases, we describe a representative case in which a single guide catheter and two over-the-wire balloon catheters were utilized in association with a single inflation device. This approach could have significant advantages over the two-inflation-device approach, based primarily on its lower cost without compromise of the effectiveness and safety of the technique.

The Corsi block-tapping task: methodological and theoretical considerations.

The Corsi block-tapping task has enjoyed extensive use in clinical and experimental studies for a quarter of a century and is arguably the single most important nonverbal task in neuropsychological research. Nevertheless, there has been considerable inconsistency not only in the administration and scoring of this measure, but also in the physical properties of the test apparatus. In this paper, we survey a wide range of studies that have made use of the block-tapping task during the past 25 years and provide a detailed appraisal of the manifold methodological variations. Additionally, we discuss the historical context in which the Corsi originated and offer a critical examination of the cognitive processing operations purported to underlie performance on this task.

Timing, mode, and predictors of death after direct angioplasty for acute myocardial infarction.

The timing and mechanisms of early (30 day) mortality in 330 consecutive patients treated with direct angioplasty less than 12 hr after onset of myocardial infarction without antecedent thrombolysis were studied. There were 38 deaths (11.5% of pts), with a majority being due to cardiogenic shock (76%). Other causes included acute closure (11%), death after emergency bypass surgery (5%), ventricular arrhythmias (5%), and respiratory failure (3%). No deaths from stroke or cardiac rupture were seen, in contrast to trials of thrombolytic agents. Most deaths were seen early, with 47% occurring within 1 day, 35% from days 2-7, and 18% from days 8-30. Death from cardiogenic shock was the most common cause of death throughout this period: 83% of deaths in days 0-3, 88% of deaths in days 4-6, and 43% of deaths in days 8-30. Significant predictors of early death included older age (P < .0001), multi-vessel disease (P < .05), direct angioplasty failure (P < .05), reduced ejection fraction (P < .0001), and anterior myocardial infarction (P < .0005). Gender, prior myocardial infarction, and prior bypass surgery did not affect mortality. Cardiogenic shock is the most common cause of early death after direct angioplasty for myocardial infarction. Patients with one or more risk factors for early death may benefit from additional myocardial salvage or revascularization efforts in the early post-infarct period. Certain causes of death after direct angioplasty (cardiac, rupture, stroke) appear to be less common than data reported for lytic therapy for myocardial infarction.

Cognitive deficits associated with human immunodeficiency virus encephalopathy.

The encephalopathy associated with direct nervous system infection by the human immunodeficiency virus (HIV) has been recognized as one of the major debilitating aspects of the acquired immunodeficiency syndrome (AIDS) and of pre-AIDS conditions. A comprehensive neuropsychological examination of symptomatic HIV-infected subjects without opportunistic cerebral disease demonstrated a distinctive pattern of cognitive deficits marked by prominent attentional impairment. Evidence of organizational and reasoning impairments also was observed, but language, visual-spatial, and memory consolidation abilities were relatively preserved. The findings suggest a profile of impairment similar to other cognitive syndromes involving dysfunction of predominantly anterior brain structures and projections and suggest a rationale for psychostimulant drug treatment.