Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via α4β2* nicotinic receptor activation

Acetylcholine (ACh) release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP)-expressing interneurons that selectively innervate other interneurons (VIP/IS) were excited by ACh through the activation of nicotinic receptors containing α4 and β2 subunits (α4β2*). ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC) barrages blocked by dihydro-β-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by α4β2* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of α4β2* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation

Usability of Food and Beverage Packs in Hospital - Experiences from the Renal Ward

Abstract presented at The 21st IAPRI World Conference on Packaging, 19-22 June 2018, Zhuhai, Chin

Neuropsychological Detection and Characterization of Preclinical Alzheimer's Disease

We attempted to characterize the changes in cognition associated with the earliest, or preclinical, stages of Alzheimer's disease (AD) by administering a comprehensive neuropsychological test battery to a group of initially nondemented older adults participating in a prospective epidemiologic study of dementia. Using Cox regression analyses, we examined the associations between baseline neuropsychological test scores and subsequent development of AD. Results confirmed preliminary findings that baseline scores on the Boston Naming Test, Immediate Recall on the Selective Reminding Test, and the Similarities subtest of the Wechsler Adult Intelligence Scale-Revised were significantly and independently associated with later diagnosis of AD. Analyses controlled for the effects of age, education, sex, and language of test administration. These results lend support to the notion of a preclinical phase of AD and indicate that this very early stage of AD is characterized by poor word-finding ability, abstract reasoning, and memory

Interrater Reliability of Extrapyramidal Signs in a Group Assessed for Dementia

Extrapyramidal signs were rated by three neurologists in 20 patients who had either been diagnosed as having probable Alzheimer's disease or who were being evaluated for dementia. In general, good inter-rater reliability was found for the presence or absence of extrapyramidal signs, although agreement over the presence of some signs was reduced when distinctions between normality and slight departures from normality were required

Safety and Efficacy of Oral Physostigmine in the Treatment of Alzheimer Disease

Results of therapeutic trials with physostigmine in the treatment of Alzheimer disease (AD) have been inconsistent and controversy persists concerning safety and efficacy. In a double-blind, placebo-controlled, crossover study, patients received 6 weeks of oral physostigmine (OP) and placebo in random order. Twenty-nine patients with AD received as much as 16 mg/day of OP and were assessed with neuropsychological and functional measures. No significant cardiac side effects were noted, though other systemic adverse effects were noted, requiring dose reduction in four patients. There was a slight but significant improvement (12%) in performance on the selective reminding test with physostigmine and the memory performance was correlated with dosage. This improvement compares favorably with the 15% decrease in scores seen in an untreated comparison cohort followed for an equivalent time period. There was a trend toward an improvement in communication and a reduction in memory complaint. These results suggest that oral physostigmine is safe and may improve memory in AD

An Estimate of the Incidence of Depression in Idiopathic Parkinson's Disease

Estimates of the prevalence of depression in idiopathic Parkinson's disease vary, but have been greater than in most comparison groups. In a survey of patients with Parkinson's disease (N = 339), the prevalence of depression was 47%. A total of 326 cases were reviewed to estimate the incidence of depression from September 30, 1984, to July 31,1989. Assessments of depression during both the prevalent and the incident periods were noted in 258 cases. There was no history of depression in 129 cases, and nine new cases occurred. The incidence rate was 1.86% per year and the cumulative risk was 8.6%. Published estimates of the incidence of depression in the general population are few. In one study, the annual incidence of depression in individuals older than 40 years was 0.17%. In another, the incidence of depression in individuals older than 50 years was 0.14% for men and 0.29% for women. Although our retrospective study probably underdiagnoses depression, the incidence of depression is increased in Parkinson's disease

Neuropsychologic Impairment in Early HIV Infection: A Risk Factor for Work Disability

Objective: To explore the functional significance of incident neuropsychologic impairment among initially asymptomatic subjects infected with human immunodeficiency virus. Design: Prospective, observational cohort study of homosexual and bisexual men to examine the incidence of work disability related to the onset of neuropsychologic impairment. Setting: A university clinical and behavioral research site in New York City. Participants: Sample of 207 homosexual and bisexual men; 123 were seropositive and 84 were seronegative. Principal Outcome Measures: Incident work disability in the course of 4.5 years of follow-up, with disability defined as a persistent (≥24 months) change in work hours (from 20 or more to less than 20 h/wk). Results: Compared with seronegative control subjects (n=72), the relative risk of work disability among initially asymptomatic seropositive men (n=44) was 2.76 (95% confidence interval, 1.2 to 6.5), nearly a threefold increase. Proportional hazards models show that this increased risk is attributable to the development of major neuropsychologic impairment in a subset (eight of 44) of the initially asymptomatic men, which is significantly associated with incident work disability (6/8 [75%]). Adjusting for symptom status and CD4+ cell count at the time of disability did not eliminate the increased risk associated with neuropsychologic impairment. Conclusions: In this cohort, the increased risk of work disability among initially asymptomatic human immunodeficiency virus—positive men was related to incident neuropsychologic impairment; such impairment predicted work disability independently of symptom status and CD4+ cell count over the follow-up period. Neuropsychologic impairment in the course of human immunodeficiency virus infection may indicate increased risk for poor outcomes over and above that associated with systemic disease

The Neuropsychological Profiles of Mild Alzheimer's Disease and Questionable Dementia as Compared to Age-Related Cognitive Decline

Test scores from a comprehensive neuropsychological battery administered to 1602 subjects consisting of 1347 subjects with probable Alzheimer's disease (AD), 100 subjects with questionable dementia (QD) and 155 non-demented elderly control subjects were cross-sectionally analyzed. Subjects with probable AD were categorized as mild (n = 244), moderate (n = 480), severe (n = 376), and very severe (n = 247) according to modified mini mental status exam (mMMSE) scores. Mean scores on individual neuropsychological tests are provided for each group of subjects. Stratified random sampling was performed to select a sample of mild AD subjects who were matched in age and education to non-demented elderly controls, and analyses focused on the performance of QD subjects and mild AD subjects, whose scores were compared to those of the elderly control subjects. Selected scores were organized by cognitive domain and logistic regressions were used to determine the domains and individual tests within each that were most predictive of group status. Results suggested a profile of scores associated with QD and mild AD including impaired recall of verbal information for both groups. Areas of lower functioning in QD subjects as compared to elderly controls included category fluency and visuospatial ability

The Columbia University Scale for Psychopathology in Alzheimer's Disease

The Columbia University Scale for Psychopathology in Alzheimer's disease is a new screening instrument developed for use by clinicians or trained lay interviewers. Interrater reliability was established between a psychiatrist and a lay interviewer in 20 patients. In an independent sample of 91 outpatients with very mild to moderate probable Alzheimer's disease, caregiver informants reported that depressed mood was common (46.2%) but rarely persistent (2.2%), and that sleep disturbance occurred frequently (41.8%) but was never severe (0%). There were significant but weak associations between the presence of specific subtypes of delusions and severity of dementia. Although a variety of delusional symptoms were reported, they were frequently transient and patients often accepted the truth if corrected by the caregiver. As a result, few patients met broad or narrow operational criteria used to define delusions. Prior studies may have overestimated the prevalence of psychotic features in Alzheimer's disease by not employing standard definitional criteria. The findings also indicate that new methodology such as that employed in this instrument needs to be evaluated more widely

Survey of University of California Academics\u27 Attitudes Regarding the Impact of Escaped Horticultural Introductions on Wildlands

In order to investigate whether there were differences in attitudes and perceptions within the University of California regarding the impact of introduced ornamental plants, we conducted a survey of academics with assignments in natural resource programs or ornamental horticulture. In general, the ornamental horticulture academics did not view the problem of invasive species as severely as the natural resource academics, but the both groups recognize that non-native landscape ornamentals now occur and can affect California\u27s wildlands. These data can be used to provide training to academics on this issue and help facilitate discussion between the different groups