Agavni Petrosyan

Is there evidence for cognitive intervention in Alzheimer disease? A systematic review of efficacy, feasibility, and cost-effectiveness.

Several studies have shown that cognitive intervention may be beneficial for people with Alzheimer disease (AD), but literature reviews conducted so far, have yielded mixed and inconclusive results. In this work, through an extensive bibliographic search, we aim: (1) to analyze the efficacy of cognitive intervention in patients diagnosed with AD; (2) to provide an estimate of the feasibility of cognitive intervention; and (3) to review available cost-effectiveness data of this approach. Four randomized controlled trials of cognitive intervention, for patients diagnosed with AD that incorporated cognitive intervention and mock intervention control conditions, were included in the analysis. Only the domain of global cognitive functioning, as measured by Mini-Mental State Examination, showed significant intervention effects. No effects were observed in the remaining domains. Concerning feasibility, high rates of completion and adherence were found. A single randomized controlled trial, with unspecified dementia, suggested cognitive intervention to be cost-effective. Given the currently available dearth of well-controlled and focused trials in AD, these results should be carefully interpreted and remain to be confirmed in the future. There is a clear need for more high-quality research.

Olfactory dysfunction in dementia

The natural aging process brings about some inevitable consequences, such as olfactory dysfunction, which is also frequently linked to numerous neurodegenerative disorders. Many age-related dementia, such as Alzheimers disease, Vascular dementia, Parkinsons disease, and Frontotemporal Dementia often display olfactory dysfunction. Despite the overwhelming evidence of above mentioned facts, the symptomatic relevance and potential clinical and pre-clinical value of olfactory dysfunction remains overlooked by many clinicians and public alike. Olfactory dysfunction has strong practical implications on daily activities and, although not as prominent as in other mammals, olfaction is still an evolutionarily relevant sense involved in human survival (e.g., smelling gas; bad food). In this work, we provide a brief review of current research related to the olfactory dysfunction profiles in different types of dementia. Additionally, we present a compilation of accessible, easy to use olfaction assessment tools; and highlight future directions in terms of improving clinical diagnosis in patient care and research.

A population study of the precedence effect

Data are reported from a population of untrained individuals under lag- and single-click conditions in a discrimination suppression precedence-effect task. The cue to be discriminated was an interaural level-difference (ILD). Each of 91 observers completed 10 runs in a two-interval forced-choice design under a lag-click condition and three runs under a single-click condition. Stimuli were 125-micros rectangular pulses and the interclick interval was 2 ms. Observers were randomly assigned to three groups of approximately 30. Each group was then tested at one stimulus intensity (43, 58, or 73 dB). Mean threshold within each group was greater than 15 dB for the lag-click condition and 6 dB for the single-click condition, although there was substantial interobserver variability. In contrast to [J. Acoust. Soc. Am. 114 (2003) 420] who reported a strong effect of intensity on lag-click ITD discrimination, no effect of intensity was observed on lag-click ILD thresholds. Analysis of over 50,000 near-threshold trials from 302 observers pooled across studies showed a spatial asymmetry in response patterns and a small, but statistically significant effect of gender. A model is proposed which shows that decay of sensory memory and increases in auditory filter bandwidths with intensity may predict the different findings for ILD versus ITD lag-click thresholds.

Non-pharmacological cognitive intervention for aging and dementia: Current perspectives

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive (e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia (mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well.

Are cognitive interventions for Multiple Sclerosis effective and feasible

PURPOSE Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. METHODS To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. RESULTS Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. CONCLUSIONS This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.

Observer weighting of interaural cues in positive and negative envelope slopes of amplitude-modulated waveforms

The auditory system can encode interaural delays in highpass-filtered complex sounds by phase locking to their slowly modulating envelopes. Spectrotemporal analysis of interaurally time-delayed highpass waveforms reveals the presence of a concomitant interaural level cue. The current study systematically investigated the contribution of time and concomitant level cues carried by positive and negative envelope slopes of a modified sinusoidally amplitude-modulated (SAM) high-frequency carrier. The waveforms were generated from concatenation of individual modulation cycles whose envelope peaks were extended by the desired interaural delay, allowing independent control of delays in the positive and negative modulation slopes. In experiment 1, thresholds were measured using a 2-interval forced-choice adaptive task for interaural delays in either the positive or negative modulation slopes. In a control condition, thresholds were measured for a standard SAM tone. In experiment 2, decision weights were estimated using a multiple-observation correlational method in a single-interval forced-choice task for interaural delays carried simultaneously by the positive, and independently, negative slopes of the modulation envelope. In experiment 3, decision weights were measured for groups of 3 modulation cycles at the start, middle, and end of the waveform to determine the influence of onset dominance or recency effects. Results were consistent across experiments: thresholds were equal for the positive and negative modulation slopes. Decision weights were positive and equal for the time cue in the positive and negative envelope slopes. Weights were also larger for modulations cycles near the waveform onset. Weights estimated for the concomitant interaural level cue were positive for the positive envelope slope and negative for the negative slope, consistent with exclusive use of time cues.

Enhanced Optomotor Efficiency by Expression of the Human Gene Superoxide Dismutase Primarily in Drosophila Motorneurons

Abstract Mutation of the human gene superoxide dismutase (hSOD1) triggers the fatal neurodegenerative motorneuron disorder, familial amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease). Broad expression of this gene in Drosophila has no effect on longevity or functional senescence. We show here that restricting expression of human SOD1 primarily to motorneurons of Drosophila has significant effects on optomotor efficiency during in-flight tracking of rapidly moving visual targets. Under high-stress workloads with a recursive visual-motion stimulus cycle, young isogenic controls failed to track rapidly changing visual cues, whereas their same-aged hSOD1-activated progeny maintained coordinated in-flight tracking of the target by phase locking to the dynamic visual movement patterns. Several explanations are considered for the observed effects, including antioxidant intervention in motorneurons, changes in signal transduction pathways that regulate patterns of gene expression in other cell types, and expression of hSOD1 in a small set of neurons in the central brain. That hSOD1 overexpression improves sensorimotor coordination in young organisms may suggest possible therapeutic strategies for early-onset ALS in humans.

Effects of interaural decorrelation and acoustic spectrum on detecting the motion of an auditory target

The ability to detect the motion of an auditory target based on dynamic changes in interaural time differences was measured as a function of interaural correlation and acoustic spectrum in a single-interval forced-choice design. Three subjects listened to headphone-presented noise containing a dynamic linear change in interaural delay (500 μs/s). The stimulus spectrum was broadband (0.1 to 10 kHz), highpass above 1.5 kHz, or lowpass below 1.2 kHz, and interaural correlation ranged from 0.1 to 1.0. Subject performance was nearly identical for the broadband and lowpass conditions, with near perfect detection for interaural correlations of 0.5 or greater, and above threshold (d′ > 1) detection for a correlation of 0.3. Performance was near random when the correlation was 0.1. In the highpass condition, performance rapidly deteriorated from substantially above threshold (d′ > 2) to random level as interaural correlation was reduced from 1.0 to 0.7. This rapid decline in performance at high frequencies may be explained in terms of interaural envelope decorrelation.

Enhanced tethered-flight duration and locomotor activity by overexpression of the human gene SOD1 in Drosophila motorneurons

Mutation of the human gene superoxide dismutase (hSOD1) is associated with the fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou Gehrig’s disease). Selective overexpression of hSOD1 in Drosophila motorneurons increases lifespan to 140% of normal. The current study was designed to determine resistance to lifespan decline and failure of sensorimotor functions by overexpressing hSOD1 in Drosophila‘s motorneurons. First, we measured the ability to maintain continuous flight and wingbeat frequency (WBF) as a function of age (5 to 50 days). Flies overexpressing hSOD1 under the D42-GAL4 activator were able to sustain flight significantly longer than controls, with the largest effect observed in the middle stages of life. The hSOD1-expressed line also had, on average, slower wingbeat frequencies in late, but not early life relative to age-matched controls. Second, we examined locomotor (exploratory walking) behavior in late life when flies had lost the ability to fly (age ≥ 60 d). hSOD1-expressed flies showed significantly more robust walking activity relative to controls. Findings show patterns of functional decline dissimilar to those reported for other life-extended lines, and suggest that the hSOD1 gene not only delays death but enhances sensorimotor abilities critical to survival even in late life.

Importance of web-based intervention in minimizing depressive symptoms and associated stigma in depressed medical students

Revista Brasileira de Psiquiatria. 2013;35 s 2013 Associac¸a˜o Brasileira de Psiquiatria LETTERS TO THE EDITOR Importance of web-based intervention in minimizing depressive symptoms and associated stigma in depressed medical students Rev Bras Psiquiatr. 2013;35:334 doi:10.1590/1516-4446-2012-0972 There is a considerable prevalence of depression in medical students, and those who are depressed more frequently endorse feeling stigmatized than non- depressed students. 1 Because concerns about confidentiality are often cited by depressed medical students as a major barrier in seeking help, there is a significant need to develop an innovative way to provide medical students with safe and confidential access to services to improve prevention, detection, and intervention in depression and its asso- ciated stigma. 1 A web-based approach could be potentially useful for addressing this issue and has already been used for delivering intervention in various health conditions, with benefits such as low cost, user convenience, timely information, privacy and confidentiality, reduced levels of stigmatization, and increased user and supplier control. 2 Moreover, although current evidence is limited, a recent meta-review 3 points to the efficacy of web-based cognitive behavioral interventions in treating/improving depression symptoms in adults. In relation to depression stigma, there is evidence that web-based interventions (e.g., MoodGYM) can reduce personal stigmatizing attitudes toward depression. The web-based approach assumes even greater importance when we consider that stigmatization increases with either the use of prescription medication or mental health counseling, and that only a small percentage of depressed medical students seek mental health counseling services, due to lack of time, con- fidentiality, stigma, and fear of documentation in aca- demic records. 4 However, unintended negative effects could easily arise with web-based approaches as well (e.g. decline in seeking support from family and friends, avoidance of in-person mental health services, inade- quate assessment and diagnosis). We should also bear in mind that it is important to target depressive symptoms in this undertreated population 4 not only for their own health but also for that of their patients. Web-based anonymous platforms could serve as screen- ing tools in helping to identify associated factors and causes of depression, and provide self-initiated interven- tion. In Portugal, the available literature and research on depression in medical students is scarce. However, one study reported a prevalence of 58.2% of clinically significant stress symptoms in a medical student popula- tion of Portugal. 5 Based on these findings, our team is currently developing a protocol to assess Portuguese medical students’ needs and the perceived relevance of a (web-based) intervention. We believe that it is imperative to develop and test the efficacy of a novel web-based program designed to meet medical students’ needs (and preferences) in their specific context, addressing risks and protective factors and stressors. Although we hypothesize/expect that an approach comprising cognitive behavioral techniques and psychoeducation will benefit this population, we believe that testing currently available tools with proven efficacy in adults might dilute their effectiveness and not benefit this population due to their experiential specificities (e.g., specificities related to health professional/medical train- ing and practice of tackling high emotional and physical demands, high level of responsibility, exposure to human physical and psychological suffering, etc.), which have the potential to translate into depression and burnout. However, later trials should further compare the efficacy of standard computer-based interventions for depression with interventions designed specifically for medical students. Jorge Alves, 1 Thomas L. Schwenk, 2 O scar F. Gonc¸alves, 1,3 Agavni Petrosyan 1,4 Neuropsychophysiology Laboratory, Center for Research in Psychology (CIPsi), School of Psychology, University of Minho, Braga, Portugal. 2 University of Nevada School of Medicine, Reno, NV, USA. 3 Department of Counseling and Applied Educational Psychology, Bouve´ College of Health Sciences, Northeastern University, Boston, USA. 4 Department of Cognitive Sciences, University of California, Irvine, CA, USA. Submitted Aug 25 2012, accepted Feb 13 2013. Disclosure The authors report no conflicts of interest. References 1 Schwenk TL, Davis L, Wimsatt LA. Depression, stigma, and suicidal ideation in medical students. JAMA. 2010;304:1181-90. 2 Griffiths F, Lindenmeyer A, Powell J, Lowe P, Thorogood M. Why are health care interventions delivered over the internet? A systematic review of the published literature. Joˆ Med Internet Res. 2006;8:e10. 3 Foroushani PS, Schneider J, Assareh N. Meta-review of the effectiveness of computerised CBT in treating depression. BMC Psychiatry. 2011;11:131. 4 Givens JL, Tjia J. Depressed medical students’ use of mental health services and barriers to use. Acad Med. 2002;77:918-21. 5 Loureiro E, McIntyre T, Mota-Cardoso R, Ferreira MA. [The relationship between stress and life-style of students at the Faculty of Medicine of Oporto]. Acta Med Port. 2008;21:209-14.