The Validity of New Memory Complaints in the Elderly

Objective: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. Design: Prospective cohort. Setting: Longitudinal, community-based study of aging and dementia. Patients: One hundred thirty-three communitydwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. Main Outcome Measures: Performance on memory tests—the Buschke Selective Reminding Test and a visual memory task—and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. Results: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P=.04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. Conclusion: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition

An Association between Head Circumference and Alzheimer's Disease in a Population-Based Study of Aging and Dementia

We investigated the association between head circumference (HC) and Alzheimer's disease (AD) in a cross-sectional population-based study of aging in North Manhattan. Six hundred forty-nine subjects underwent neurologic, neuropsychological, and anthropometric evaluations; apolipoprotein E (apoE) genotype was available for a subsample of 300 individuals. Logistic regression analyses were performed with AD the outcome of interest to evaluate any association between HC and AD. In these analyses, HC evaluated as a continuous variable was associated with AD (OR 0.8, 95% CI 0.7-0.9) after adjusting for age, education, and ethnicity, gender, and height. Analyses suggested that increased risk resided mainly in those with smallest HC. Thus, women whose HC was within the lowest quintile of HC for women were 2.9 (95% CI 1.4-6.1) times more likely to have AD, after adjusting for age, education, and ethnicity; and men in the lowest quintile of HC (for men) were 2.3 times more likely to have AD (95% CI 0.6-9.8). There was no confounding by height, weight, or apoE genotype. The results are consistent with previous studies that suggest that premorbid brain size may influence the age-specific risk for AD. Future epidemiologic studies seeking environmental risk factors for AD may benefit by making HC measurements on all subjects to decrease the variance associated with other potential risk factors

An olfactory \u27stress test\u27 may detect preclinical Alzheimer\u27s disease

Background: The olfactory bulb (OB) receives extensive cholinergic input from the basal forebrain and is affected very early in Alzheimer’s disease (AD). We speculated that an olfactory ‘stress test’ (OST), targeting the OB, might be used to unmask incipient AD. We investigated if change in olfactory performance following intranasal atropine was associated with several known antecedents or biomarkers of AD. Methods: We measured change in performance on the University of Pennsylvania Smell Identification Test (UPSIT) in the left nostril before (20-items) and after (remaining 20-items) intranasal administration of 1 mg of atropine. We administered cognitive tests, measured hippocampal volume from MRI scans and recorded Apolipoprotein E genotype as indices relevant to underlying AD. Results: In a convenience sample of 56 elderly individuals (14 probable AD, 13 cognitive impairment no dementia, 29 cognitively intact) the change in UPSIT score after atropine (‘atropine effect’ = AE) correlated significantly with demographically scaled episodic memory score (r = 0.57,

Djinn Lite: a tool for customised gene transcript modelling, annotation-data enrichment and exploration

BACKGROUND: There is an ever increasing rate of data made available on genetic variation, transcriptomes and proteomes. Similarly, a growing variety of bioinformatic programs are becoming available from many diverse sources, designed to identify a myriad of sequence patterns considered to have potential biological importance within inter-genic regions, genes, transcripts, and proteins. However, biologists require easy to use, uncomplicated tools to integrate this information, visualise and print gene annotations. Integrating this information usually requires considerable informatics skills, and comprehensive knowledge of the data format to make full use of this information. Tools are needed to explore gene model variants by allowing users the ability to create alternative transcript models using novel combinations of exons not necessarily represented in current database deposits of mRNA/cDNA sequences. RESULTS: Djinn Lite is designed to be an intuitive program for storing and visually exploring of custom annotations relating to a eukaryotic gene sequence and its modelled gene products. In particular, it is helpful in developing hypothesis regarding alternate splicing of transcripts by allowing the construction of model transcripts and inspection of their resulting translations. It facilitates the ability to view a gene and its gene products in one synchronised graphical view, allowing one to drill down into sequence related data. Colour highlighting of selected sequences and added annotations further supports exploration, visualisation of sequence regions and motifs known or predicted to be biologically significant. CONCLUSION: Gene annotating remains an ongoing and challengingtask that will continue as gene structures, gene transcription repertoires, disease loci, protein products and their interactions become moreprecisely defined. Djinn Lite offers an accessible interface to help accumulate, enrich, and individualise sequence annotations relating to a gene, its transcripts and translations. The mechanism of transcript definition and creation, and subsequent navigation and exploration of features, are very intuitive and demand only a short learning curve. Ultimately, Djinn Lite can form the basis for providing valuable clues to plan new experiments, providing storage of sequences and annotations for dedication to customised projects. The application is appropriate for Windows 98-ME-2000-XP-2003 operating systems

A Preliminary Study of Apolipoprotein E Genotype and Psychiatric Manifestations of Alzheimer's Disease

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations

Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor

The receptor for the inhibitory neurotransmitter glycine is a member of the ligand gated ion channel recep tor superfamily. Point mutations in the gene encoding the alpha 1 subunit of the glycine receptor channel complex (GlyR) have recently been identified in pedigrees with the autosomal dominant neurological disorder, startle disease (hyperekplexia). These mutations result in the substitution of leucine or glutamine for arginine 271. This charged residue is located near the ion channel region and is predicted to affect chloride permeation through the GlyR. We found little evidence for this role from the anion/cation selectivity and lack of pronounced rectification of currents flowing through recombinant human alpha 1 subunit GlyRs containing the startle disease mutations. We reveal, however, that the startle disease mutations profoundly disrupt GlyR func tion by causing 230-410-fold decreases in the sensitivity of receptor currents activated by the agonist glycine. Additionally, we report corresponding 56- and 120-fold reductions in the apparent binding affinity (K-i) of glycine to the mutant GlyRs, but no change in the binding affinity of the competitive antagonist, strychnine. Thus, startle disease reduces the efficacy of glycinergic inhibitory neurotransmission by producing GlyRs with diminished agonist responsiveness. Our results show that startle disease mutations define a novel receptor activation site

Consistency of Clinical Diagnosis in a Community-Based Longitudinal Study of Dementia and Alzheimer's Disease

We evaluated the consistency of the diagnosis of dementia in a multicultural, longitudinal community-based study of cognitive impairment and dementia. We diagnosed dementia using a fixed neuropsychological paradigm; the diagnosis also required historical evidence of functional impairment. In a sample of 656 subjects with at least one annual follow-up examination, dementia was confirmed at 1 year in 89% of the 304 subjects initially demented, and in 90% of the 136 subjects with the initial diagnosis of probable Alzheimer's disease (AD). The 34 initially demented subjects who failed to meet criteria for dementia at follow-up included 13 with an initial diagnosis of probable AD. All 34 still had evidence of cognitive impairment; this group was more likely to have a history of pulmonary disease, multiple medication use, or chronic alcohol use than other demented patients. Consistency of dementia diagnosis did not vary according to educational attainment or ethnic background. The use of a neuropsychological paradigm such as ours in large longitudinal studies of dementia may minimize interobserver diagnostic variability or diagnostic drift over time while contributing the benefits of a comprehensive cognitive evaluation to the diagnostic process

Nightingallery: theatrical framing and orchestration in participatory performance

The Nightingallery project encouraged participants to converse, sing, and perform with a musically responsive animatronic bird, playfully interacting with the character while members of the public could look on and observe. We used Nightingallery to frame an HCI investigation into how people would engage with one another when confronted with unfamiliar technologies in conspicuously public, social spaces. Structuring performances as improvisational street theatre, we styled our method of exhibiting the bird character. We cast ourselves in supporting roles as carnival barkers and minders of the bird, presenting him as if he were a fantastical creature in a fairground sideshow display, allowing him the agency to shape and maintain dialogues with participants, and positioning him as the focal character upon which the encounter was centred. We explored how the anthropomorphic nature of the bird itself, along with the cultural connotations associated with the carnival/sideshow tradition helped signpost and entice participants through the trajectory of their encounters with the exhibit. Situating ourselves as secondary characters within the narrative defining the performance/use context, our methods of mediation, observation, and evaluation were integrated into the performance frame. In this paper, we explore recent HCI theories in mixed reality performance to reflect upon how genre-based cultural connotations can be used to frame trajectories of experience, and how manipulation of roles and agency in participatory performance can facilitate HCI investigation of social encounters with playful technologies. © 2014 Springer-Verlag London

Frequency dependent specific heat of viscous silica

We apply the Mori-Zwanzig projection operator formalism to obtain an expression for the frequency dependent specific heat c(z) of a liquid. By using an exact transformation formula due to Lebowitz et al., we derive a relation between c(z) and K(t), the autocorrelation function of temperature fluctuations in the microcanonical ensemble. This connection thus allows to determine c(z) from computer simulations in equilibrium, i.e. without an external perturbation. By considering the generalization of K(t) to finite wave-vectors, we derive an expression to determine the thermal conductivity \lambda from such simulations. We present the results of extensive computer simulations in which we use the derived relations to determine c(z) over eight decades in frequency, as well as \lambda. The system investigated is a simple but realistic model for amorphous silica. We find that at high frequencies the real part of c(z) has the value of an ideal gas. c'(\omega) increases quickly at those frequencies which correspond to the vibrational excitations of the system. At low temperatures c'(\omega) shows a second step. The frequency at which this step is observed is comparable to the one at which the \alpha-relaxation peak is observed in the intermediate scattering function. Also the temperature dependence of the location of this second step is the same as the one of the $\alpha-$peak, thus showing that these quantities are intimately connected to each other. From c'(\omega) we estimate the temperature dependence of the vibrational and configurational part of the specific heat. We find that the static value of c(z) as well as \lambda are in good agreement with experimental data.Comment: 27 pages of Latex, 8 figure