Improving Sensitivity of Early Detection of Alzheimer’s Disease via Multidimensional Analysis of Longitudinal Magnetic Resonance Scans

Statistics show that two per cent of Canadians aged 60-74 years, and one-third over the age of 85, suffer from Alzheimer's disease and related dementias. By 2031, more than 750,000 Canadians are expected to have Alzheimer's disease and related dementias. The social and financial costs of managing people with these conditions is significant and puts a severe strain on families and on the health system. Sadly, by the time Alzheimer’s symptoms are recognized and confirmed, there is often substantial irreversible neurodegenerative damage. Current methods of diagnosing Alzheimer’s disease are frustratingly inexact. Lacking ways to identify the onset of disease within the brain itself, clinicians instead look for telltale symptoms, such as failing memory. Even when the disease has progressed and structural changes become apparent on magnetic resonance imaging (MRI) scans, neurologists do not have tools to precisely measure how advanced the disease is, relying instead on visual inspection. Dr. Faisal Beg is trained in engineering, biology and mathematics. Drawing from international MRI databases containing the brain scans of hundreds of older adults with and without Alzheimer’s, he is taking precise measurements to pinpoint where and how brain structures change with the onset of the disease. It’s a complex analysis, made even more challenging due to the normal variations seen in brain shape, size and structure. Beg anticipates that his research will help take the guesswork out of diagnosing Alzheimer’s disease, especially in its early stages. In the longer term, it also may contribute to more accurate assessments of whether new Alzheimer’s drugs are effective in slowing or halting progression of the disease

Stress-hormone production and health: the importance of forgiveness

When they are functioning well, intimate relationships contribute to better health and increased longevity. A cornerstone of well-functioning relationships is the ability to forgive a partner for relationship transgressions, such as telling lies, flirting with another person, or saying hurtful things. Repairing a relationship following the hurtful actions of one partner has consequences, not only for relationship quality, but also for physical health. One way that the act of forgiveness may be associated with health relates to cortisol production. Cortisol is a hormone released by the adrenal gland during times of stress. Chronic elevations of cortisol have negative effects on cardiovascular, immune, and brain systems and potentially increase the risk for diabetes, hypertension, immune system deficiency, and other illnesses. Being unforgiving has been shown to produce cortisol in a similar pattern to that which is experienced during other stress responses. Kim Watt is examining whether cortisol production is a mechanism for the link between forgiveness and general physical health. She is conducting her study with 200 newlywed couples, recording their physical health and measuring their cortisol levels at baseline and following a set of emotionally stressful marital discussions. Results from this study will contribute to a clearer understanding of the risk pathways by which negative relationship processes may lead to poor physical health. This may suggest that a focus on strengthening close relationships by improving couples’ skills when discussing relationship issues is a way of ultimately reducing health problems.

Multimodal Imaging Instrumentation for Non-Invasive Functional Retinal Imaging

With an aging population comes an increase in a number of diseases and conditions of the eye. A recent advance in imaging – called optical coherence tomography (OCT) – provides a non-invasive way to create high resolution, cross-sectional images of inside the eye. OCT is particularly useful in providing these images of the retina, showing cross sectional images of the various layers with resolution equivalent to a low-power microscope and better than other imaging techniques such as magnetic resonance imaging (MRI).

A new technological development called Fourier Domain (FD) OCT provides these images much more quickly than existing systems. It has also been successful in creating three-dimensional images of the retina, which were previously not possible to obtain. However, clinical use of FD OCT is limited as it generates only an image of the eye’s structures, without providing any functional information about the biological processes at play.

Dr. Marinko Sarunic’s research builds on earlier work where he successfully combined FD OCT imaging with molecular contrast capabilities to provide functional information. He is now using this technology to determine its usefulness in retinal diagnostics, the study of disease processes, and the testing of new drugs and therapies. Development of FD OCT imaging techniques will help physicians better understand and manage ophthalmic conditions, through high resolution visualization and improved minimally-invasive, image-guided procedures.

The impact of therapeutic design on social engagement among residents with dementia during programmed activities in dementia care units

Dementia special care units (SCU) and freestanding special care facilities (SCF) for people with dementia are built using design principles that have been shown to enhance quality of life and reduce responsive behaviours that often occur when residents are disoriented or overstimulated by their surroundings. More supportive environments in these facilities are created through smaller unit sizes, homelike ambience, increased wayfinding, smaller activity spaces, and access to safe and secure wandering paths. Architectural planning and design features can improve the physical context where programmed activities such as music therapy, exercise sessions, creative arts, and therapy gardening occur. However, these specially designed spaces offer few therapeutic benefits without appropriate staff resources and family involvement to make the programs succeed, and consideration must be given to the combined effects of physical design, programs and policies, and staffing issues. Few studies have systematically assessed how modifications to the physical environment work in concert with social and organizational factors to enhance opportunities for residents to engage in positive social interactions through meaningful programmed activities. Krista Frazee is exploring the impact of the physical and social environments of care settings on residents’ social engagement during programmed activities in SCUs and SCFs, versus traditional integrated care facilities. She will also assess staff and family caregiver perceptions of activity spaces in helping them provide meaningful planned activities for residents. The findings from this study will be used to inform architects, interior designers, facility administrators and staff in various ways they can support the care and quality of life of residents with dementia through the integration of physical design and programmed activities.

New Perspectives on Gender, Diversity, and Health Policy, Planning, and Services

The primary methods for identifying and responding to differences between men and women in the health context are gender-based and gender-sex-based analyses (GBA/GSBA). While these approaches are intended to consider diversity within each group, they do not always capture how gender interacts with other factors such as race/ethnicity, socio-economic status, sexual orientation, geography, ability and age. Not taking these factors into account in health planning, implementation and research can result in real economic and human costs for health care consumers. These include lost opportunities, ill health, suffering and perhaps overall, an ineffective and inequitable health care system. A key challenge facing researchers and policy makers is how to move beyond singular variables (e.g. gender) to understand the complex dynamics at play between gender and health. Dr. Olena Hankivsky is examining how GBA and GSBA are applied in health planning, services and policy in Canada, Sweden, the UK, Australia and the Ukraine. She is exploring innovative improvements for analyzing gender and diversity in a health context. In particular, Hankivsky is conducting a gender and diversity analysis of the most recent health reform initiative in British Columbia — The Conversation on Health. The findings could contribute to developing policy tools and interventions that will improve the effectiveness and efficiency of health services and programs for vulnerable and marginalized populations in BC, Canada, and internationally.

CD-based ELISA for point-of-care diagnostics

Current methods of medical diagnostics, such as imaging and laboratory tests, tend to be time-consuming, labour intensive, and often limited to biomedical laboratories or hospital settings that have specialized equipment. In contrast, point-of-care diagnostic tools allow testing and diagnosis to be performed in a doctor’s office, at a significantly reduced cost and in a shorter time to obtain test results. This contributes to faster treatment decisions and better follow-up post treatment. The enzyme-linked immunosorbent assay (ELISA) is a popular tool for analyzing environmental or biomedical samples. The ELISA method uses a number of biochemical steps to detect the presence of a specific protein (such as an antigen or antibody) in a sample on a microscope slide, which is read by a robotic spotter or microplate reader. Preliminary research has suggested that these bioassays could be prepared on the surface of a compact disc (CD), and the results could be read by a standard computer drive equipped with special software. With commercialization, this method would undoubtedly reduce the cost of biomedical screening. Miao-Ling Ou is developing a diagnostic assay for detecting thrombin using this CD technology. Thrombin is a blood clotting factor that is the focus of many research studies on anticoagulation and cardiovascular disease therapy. Once fully developed, this CD-based ELISA method could be extended to other types of biomolecular interactions, such as those used in the screening of gene mutations or antibody-antigen interactions.

Nonverbal Emotion Processing Across Communication Channels

Nonverbal communication – facial expressions, gestures, posture, and intonation (tone of voice) – offers a rich source of information about a speaker’s intentions and moods. Recognizing and correctly interpreting these cues is important for social competence, but is challenging for people with autism and other developmental disorders that have deficits in nonverbal communication. Intonation and facial expressions represent the most prominent and biologically important nonverbal communication channels. These channels typically overlap in terms of the information they convey. While few studies have looked at the shared and unique brain mechanisms involved in these communication systems, some behavioural research suggests shared underlying mechanisms. Using magnetoencephalography, an imaging technique used to detect electro-magnetic and metabolic shifts occurring in the brain, Valery Sramko is studying both typically developing adults and those with autism spectrum disorder. Sramko is examining the mechanisms and brain areas shared by intonation and facial expression, which are deficient in people with autism, to shed light on nonverbal emotion processing. Her overall aim is to gain a better understanding of the processes and mechanisms involved in nonverbal communication, which could contribute to the development of potential interventions for people with autism and other developmental disorders.

Pathogen bioinformatics and the evolution of microbial virulence

Infectious diseases are responsible for roughly a third of annual deaths worldwide and contribute greatly to productivity loss. Antimicrobial resistance and newly emerging diseases are both cause for significant concern. With the advent of microbial whole-genome sequencing, there has been renewed optimism that computational analyses of microbial genomes will allow for faster identification of promising new therapeutic targets, which can then be further investigated with laboratory studies. At the moment, however, current computational practices are not accurate enough to be truly effective. Dr. Fiona Brinkman is interested in improving computational methods used to identify new potential bacterial vaccine components or drug/diagnostic targets. She is focusing in particular on improving identification methods for two regions: bacterial cell surface and secreted proteins, since they are the most accessible targets; and clusters of genes called genomic islands, which appear to disproportionately contain virulence genes and so could aid investigations of bacterial pathogenicity. Her research group is also studying the evolution of microbial virulence, both from the pathogen and host perspective, using bioinformatic approaches supported by laboratory studies. This work aims to develop methods and insights that may accelerate the identification of promising new targets from pathogen genomes. With the ability to analyze multiple infectious disease-causing microbes in parallel, this research has the potential to have a wide reaching impact on efforts to control multiple infectious diseases.

Biomechanical energy harvesting

Electronic medical devices such as vital sign monitors, pacemakers and motorized prostheses are relied upon by people with disabilities, the elderly and others. However, all of these mobile devices are powered by batteries, which have limited energy storage, and add additional weight to the devices. Although substantial progress has been made in enhancing battery capacity, power requirements for the mobile devices are increasing faster than the improvements made in battery performance. Human power is an attractive energy source because of the ability for humans to convert food into mechanical power and the high mechanical power outputs attainable by humans. Human power is portable, environmentally friendly, and readily available for power-consuming applications that involve direct human use, such as prostheses. Qingguo Li is part of an SFU research team who has developed a biomechanical energy harvester (BEH) that converts mechanical energy extracted from human movement into electrical energy. Resembling a leg brace, the BEH works by acquiring the mechanical power produced by muscles at the knee joint when the user is walking. The technology is similar to regenerative braking in hybrid gas-electric automobiles; instead of dispersing mechanical energy as heat using conventional brakes, the energy is converted into electrical energy. Li’s goal is to develop a family of energy harvesting devices that can be worn on the body, inserted into motorized prostheses or permanently implanted within the body.

Transcriptional regulation of genes in health and disease

The human genome contains all the genes, and their regulatory instructions, required to develop the human body and determine how it deals with the outside environment. Now that the genomes of many species have been sequenced, a major focus of genomics is to identify all gene regulatory elements within DNA sequences. How these building blocks of life work together to build a complex human body – with its different organs, tissues, and cell types – is not well understood. Although most human cells carry the entire genome, each cell is functionally different, suggesting that not all genes are equally expressed.

Gene expression – the full use of information in a gene – is regulated in several ways, including by transcription. Specific regulatory proteins called transcription factors bind to targeted DNA sequences in the genome. This kind of activity can control cells by switching gene expression on and off. To better understand transcription regulation in genes, and thereby better understand gene expression, binding sites for transcription factors have to be identified. It is a fundamental step in the analysis of gene expression, which is tightly regulated so that genes are only expressed in specific cells, at specific developmental stages, and at appropriate levels to ensure correct physiological function.

Dr. Jack Chen’s work investigates the properties of transcription factor binding sites (TFBSs) and determines how these properties can assist with effective genome-wide TFBS identification. Using the nematode C. elegans as the model organism, he will combine experimental and computational approaches to characterize the properties of TFBSs that distinguish functional DNA sequences from nonfunctional ones. This study may pave road for a deep understanding of transcription in C. elegans, which will in turn shed light on both healthy and dysfunctional transcription in humans.