Bioenergetic and inflammatory systemic phenotypes in Alzheimer's disease APOE ε4-carriers.

We examined the impact of an APOE ε4 genotype on Alzheimer's disease (AD) subject platelet and lymphocyte metabolism. Mean platelet mitochondrial cytochrome oxidase Vmax activity was lower in APOE ε4 carriers and lymphocyte Annexin V, a marker of apoptosis, was significantly higher. Proteins that mediate mitophagy and energy sensing were higher in APOE ε4 lymphocytes which could represent compensatory changes and recapitulate phenomena observed in post-mortem AD brains.

Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients.

Introduction: Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking.

Methods: We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tolerability.

A Mitochondrial Biomarker-Based Study of S-Equol in Alzheimer's Disease Subjects: Results of a Single-Arm, Pilot Trial.

Reductions in bioenergetic fluxes, mitochondrial enzyme activities, and mitochondrial number are observed in Alzheimer's disease (AD). Preclinical work indicates estrogen pathway signaling by either estrogen or selective β estrogen receptor (ERβ) agonists benefits these parameters. To assess whether an ERβ agonist could improve mitochondrial function in actual AD subjects, we administered S-equol (10 mg twice daily) to 15 women with AD and determined the platelet mitochondria cytochrome oxidase (COX) activity before initiating S-equol (lead-in), after two weeks of S-equol (active treatment), and two weeks after stopping S-equol (wash-out).

Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients.

A degradation product of APOE ε4-encoded apolipoprotein E protein targets mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young adult APOE ε4 carriers show reduced COX activity. To further explore relationships between APOE alleles and COX, we measured platelet mitochondria COX activity in AD subjects with (n=8) and without (n=7) an APOE ε4 allele and found the mean COX activity, when normalized to sample total protein, was lower in the APOE ε4 carriers (p<0.05).

Safety of disclosing amyloid status in cognitively normal older adults.

Introduction: Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk.

Methods: We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure.

Results: Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid).

Tolerability and pharmacokinetics of oxaloacetate 100 mg capsules in Alzheimer's subjects.

Bioenergetics and bioenergetic-related functions are altered in Alzheimer's disease (AD) subjects. These alterations represent therapeutic targets and provide an underlying rationale for modifying brain bioenergetics in AD-affected persons. Preclinical studies in cultured cells and mice found that administering oxaloacetate (OAA), a Krebs cycle and gluconeogenesis intermediate, enhanced bioenergetic fluxes and upregulated some brain bioenergetic infrastructure-related parameters.

Safety and Tolerability of R(+) Pramipexole in Mild-to-Moderate Alzheimer's Disease.

Alzheimer's disease (AD) is an aging-related, degenerative brain disease of adults. Most (∼95%) of AD occurs sporadically and is associated with early-appearing deficits in brain regional glucose uptake, changes in cerebrospinal fluid (CSF) AD-related proteins, regional brain atrophy, and oxidative stress damage. We treated mild-moderate AD individuals with R(+)-pramipexole-dihydrochloride (R(+)PPX), a neuroprotective, lipophilic-cation, free-radical scavenger that accumulates into brain and mitochondria.

Handwriting with a preferred retinal locus for AMD with scotomas.

Purpose: Individuals with macular scotomas from age-related macular degeneration frequently have difficulty writing legibly. The purpose of this study was to investigate the causes of this difficulty by documenting the location of the retinal image of the pen used for writing in relation to the scotoma and fixational preferred retinal locus (fPRL).

Methods: Subjects with macular scotomas from age-related macular degeneration and visually normal age-matched controls wrote words while observing their hand, pen, and text in a scanning laser ophthalmoscope.

Preferred retinal locus--hand coordination in a maze-tracing task.

Purpose: Fine manual tasks require coordination of vision, eye movements, and motor control. Macular scotomas from age-related macular degeneration (AMD) may adversely affect this coordination. The purpose of this research was to find whether the preferred retina locus for fixation (fPRL) also guided the hand in performing fine manual tasks and how the fingers, fPRL, and scotomas interacted in task performance.

The psychosocial benefits of alcoholics anonymous.

A quasi-experimental design was implemented to evaluate the attitudes of alcoholics toward themselves and others after they had worked all twelve steps of an AA program compared to those who had not yet completed all twelve steps. One hundred individuals who were attending AA meetings were selected so that one half had completed all of the steps and the other half had not. Participants were tested in individual sessions during which they completed a series of questionnaires.

Learning proficiency on the Wisconsin Card Sorting Test in people with serious mental illness: what are the cognitive characteristics of good learners?

Although it is widely accepted that schizophrenia and other serious mental illnesses (SMI) are associated with neurocognitive difficulties, there is great variability in neurocognitive functioning across individuals. In recent years, a growing number of schizophrenia studies have utilized the concept of learning potential to explore individual variation in cognition. Learning potential refers to the ability to benefit from instruction and is measured by assessing test performance before and after training.

Knowledge of grocery shopping skills as a mediator of cognition and performance.

Objective: Cognitive impairments in serious mental illness are associated with poorer community outcomes; yet the mechanisms through which cognition limits functioning are unknown. This study examined knowledge of grocery shopping skills as a mediator of cognition and performance of grocery shopping skills.

Methods: Fifty-one individuals with serious mental illness were administered measures of cognition, as well as measures of knowledge and performance of grocery shopping skills.

The influence of cognitive variables on recovery in depressed inpatients.

Forty two unipolar depressed inpatients were assessed on admission to hospital and again two years after the onset of the index episode. Fifty seven per cent of the sample (n = 24) fulfilled NIMH recovery criteria within this period. Older age, female gender, severity of index episode, median prior duration of episode, higher levels of dysfunctional attitudes and low self-esteem significantly predicted chronicity of depression.

The effects of hypnosis, context reinstatement, and anxiety on eyewitness memory.

The effects of hypnosis, context reinstatement, and motivational instructions on accuracy of recall for factual information and facial recognition accuracy following a stressful event were assessed. None of the three techniques had a significant effect on factual memory or susceptibility to suggestion as assessed by true-false and multiple-choice tests. However, participants high in hypnotic susceptibility showed somewhat better memory on the true-false test, and hypnosis affected performance on the two photograph line-ups.

An evaluation of the predictive validity and inter-rater reliability of clinical diagnostic criteria for senile dementia of Lewy body type.

Several recent autopsy studies suggest that senile dementia of Lewy body type (SDLT) may be the second most common neuropathologic cause of dementia in the elderly, accounting for 7 to 30% of all cases. Operational criteria for the antemortem clinical diagnosis of SDLT have already been proposed by our group. The performance of these is now examined by randomizing the case notes from a new series of SDLT, Alzheimer, and multi-infarct dementia patients for psychiatric assessment by four raters of varying clinical experience and blind to pathologic diagnosis.

Platelet intracellular calcium in patients with recurrent affective disorders.

Forty-four subjects with a history of a major recurrent affective disorder in remission and who were either on no medication or taking a single dose of psychotropic medication were conscripted together with matched controls. The fluorescent indicator fura 2 was used to measure intracellular calcium in platelets and estimations were made of total serum and ionised calcium as well as of whole blood serotonin. Intracellular calcium was measured in the resting state as well as after stimulation with thrombin, platelet activating factor and serotonin.

Committee: United Way not only way for non-profits.

Business and government should consider opening up their payroll deduction systems to a few more federated fund raising drives, claims the author. His article outlines the concerns about admissions and allocations of United Way in serving philanthropic pluralism.

Radiation-induced peritoneal mesothelioma.

A case report of a patient who developed peritoneal mesothelioma 7 years after internal and external irradiation for carcinoma of the cervix is reported. No previous reports of induction of this tumor by irradiation have been found. The subject of radiation-induced tumors and peritoneal mesothelioma is briefly discussed.