Breakthroughs

Breakthroughs; Brain images

The causes of the dementias (Alzheimer's disease being the most prevalent) are still poorly understood and lack substantial therapies. The path to finding meaningful treatments is to uncover the causes of the changes in the brain that lead to cognitive decline and to develop interventions that build on this knowledge. OHSU scientists have been engaged for over three decades in identifying the root causes of dementia as well as testing many therapies. These therapies range from preventing the onset of dementia to helping people manage and cope when symptoms emerge.

Promising research

Mechanisms of disease

The brain’s waste cleaning system

Media coverage of journal articles
Dearth of Water Channels a Sign of 'Glymphatic' Breakdown in Alzheimer's?

Alzforum.org

Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains
JAMA Neurology

The effects of noncoding aquaporin-4 single-nucleotidepolymorphisms on cognition and functional progression of Alzheimer's disease Alzheimer's & Dementia: Translational Research & Clinical Interventions

The emerging relationship between interstitial fluid-cerebrospinal fluid exchange, amyloid-β and sleep
Biological Psychiatry

Diagnosis and assessment

Seeing the living brain: Neuroimaging

Over 20 years ago we were the first to show that loss of brain tissue in the hippocampus (a critical structure for memory function) seen on MRI scans was associated with future development of dementia in the elderly. We went on to show that the rate of loss of brain accelerated with the impending onset of dementia and that signatures of microvascular disease (called "white matter lesions") were the earliest predictors on MRI of potential future cognitive decline.

White matter tracts from 3T in vivo human diffusion imagingRecently, Dr. Lisa Silbert and her team have identified unique characteristics of blood flow to the brain that allow researchers to identify critical regions of tissue that are susceptible to low blood flow and thus future damage leading to the white matter lesions. This information, coupled with revolutionary new imaging techniques called PET scans, available at OHSU, visualize for the first time in living people the pathology that Dr. Aloysius "Alois" Alzheimer described over a hundred years ago, is leading to an entire new approach to developing effective therapies.

Learn more about our Neuroimaging Lab

EVALUATE-AD: A system for at-home assesment

All clinical research for the past century to this day has relied on episodic clinic visits and self-report of symptom changes and events. Relying on this approach especially for people with memory impairment is challenging. It creates great research imprecision and barriers to developing effective therapies. 

Dr. Jeffery Kaye and his team have developed the first technology system that allows researchers to unobtrusively assess at home how a person, as well as a caregiver, are functioning in real time. This has opened up a revolution in how we can determine whether therapies are truly effective. Importantly, this approach promises to speed the process of clinical drug trials themselves.

The first study (called "EVALUATE –AD": Ecologically Valid, Ambient, Longitudinal and Unbiased Assessment of Treatment Efficacy in Alzheimer's Disease) of couples (one with Alzheimer's disease, the other a care partner) employing this technology to determine how effective current standard Alzheimer's therapies are at a level of detail never before possible has begun.

Treatment and management

I-CONECT: Modern internet-based video chat

Decades of research have shown that social interaction is critical for our health. Individuals in social isolation are shown to have a higher risk of mortality, as well as a higher incidence of cognitive impairment, including Alzheimer's disease.

More than six years ago, Dr. Hiroko Dodge and her team started a unique behavioral intervention study to examine whether conversations with study staff using modern internet-based video chat technology could improve cognitive functions. Their first pilot study resulted in encouraging findings, so Dr. Dodge and her team are now working on a new 5-year-long project, partnering with Meals on Wheels People for recruiting seniors. The new study also examines possible mechanisms of its efficacy using functional magnetic resonance imaging (fMRI). 

The study is funded by NIH and is one of the few behavioral randomized controlled trials focusing on social interactions in the oldest old segment of the population, in which social isolation is becoming a significant social issue. The recruitment process, implementation of modern communication technologies, and the results obtained in these trials have been forming an essential and highly valuable foundation for future behavior-based dementia prevention and intervention trials.

Visit the study's website.

View this study on ClinicalTrials.gov

Related journal articles
Social networks: Better together
Nature International Weekly Journal of Science

Dr. Dodge's pilot study, referenced in Nature International Weekly Journal of Science (article above):
Web-enabled Conversational Interactions as a Means to Improve Cognitive Functions: Results of a 6-Week Randomized Controlled Trial

Alzheimer's & Dementia: Translational Research & Clinical Interventions

SHARP: Walking and social engagement

Walking and social engagement may reduce African Americans' risk for Alzheimer's disease and other dementias while improving cognitive function. Yet for some older African Americans in N/NE Portland, finding motivation to begin neighborhood walking and social interaction can be difficult in the face of neighborhood change.

The Sharing History through Active Reminiscence and Photo-imagery (SHARP) pilot program, led by Dr. Raina Croff and ORCATECH staff, uses a unique combination of smart-phone technology and neighborhood history to motivate participants aged 55 and older to complete up to 72 small-group walks in 6 months. Using a tablet device, walking groups select from a menu of 1-mile routes in Portland's historically African American neighborhoods. Routes are themed (e.g. Nightlife, School Days, Food and Markets) and display historical neighborhood images approximately 10 minutes apart to prompt conversational reminiscence. Participants' recorded neighborhood stories will be integrated into community learning sessions that celebrate the local African American past while educating about healthy aging.

Related articles
 
Walk On
Oregon Humanities

Preserving memories to maintain cognitive health
OHSU News

SHARP project update: Reflecting on successes and looking toward the future
Oregon Prevention Research Center newsletter, page 10

Black seniors test reminiscing to guard against Alzheimer's
AP News

Can reminiscing improve brain health for black seniors?
Oregon Public Broadcasting - Think Out Loud

Walking, talking, and thinking about brain and body health
NIH Newsroom 

Telemedicine dementia care

Researchers from the Layton Center demonstrate the Telehealth SystemResearchers from the Layton Center demonstrate Telehealth System

Our researchers are developing unique telehealth technology options to support families and caregivers throughout the state and beyond. Our work established the reliability of the Montreal Cognitive Assessment (the MoCA) when used with telehealth technology. This can allow doctors to remotely assess patients with memory problems. Currently, we have two studies that explore how telehealth can be used to support caregivers using video conferencing. We're finding that caregivers like the ease of connecting and the convenience of receiving support in their own homes.

One of our studies, Tele-STAR, is expanding the boundaries of caregiver support. Learn more.

Related journal article
Dementia Care Comes Home: Patient and Caregiver Assessment via Telemedicine
The Gerontologist

The PUFA study: Preventing vascular dementia

Vascular risk factors such as hypertension, cardiovascular disease, atherosclerosis, type 2 diabetes and obesity play a role in increasing the risk of dementia, including Alzheimer's disease. Diet and nutrition may mediate the effects of vascular risks for dementia.

Dr. Lynne Shinto and her team are studying the role of fish oils in the only randomized controlled clinical trial that is using brain MRI to evaluate the effects of fish oil versus placebo oil in people 75 years and older who possess vascular risks for dementia. The study is highly innovative in its approach, using MRI to evaluate treatment effects on brain changes over a three year treatment period. The study has the potential to offer a cost-effective therapy for dementia prevention.

A potential plant-based treatment for Alzheimer's

Modern scientific techniques applied to ancient knowledge may help identify new treatments for Alzheimer's disease.

A team at OHSU led by Drs. Amala Soumyanath, Nora Gray and Joseph Quinn is researching the biological and chemical basis of Centella asiatica's reputation as a memory enhancing herb, as demonstrated in animal models and limited human studies. The group has shown that, both in cultured neuronal cells, and in animal brains, Centella treatment improves antioxidant status, mitochondrial activity, dendritic branching, and potentially synapse formation, all of which are impaired in Alzheimer's disease. Centella's major active compounds have been identified as triterpenes and caffeoylquinic acids. Analytical methods have been developed to measure these compounds and their potential metabolites in a variety of sample matrices.

The biological and clinical focus at OHSU is supported by collaborators at Oregon State University (Drs. Frederick Stevens and Claudia Maier) for chemical and analytical expertise. The group is continuing its preclinical exploration of Centella while developing a standardized product for use in a future clinical trial in subjects with Alzheimer's disease.

Related journal articles
Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action
International Journal of Alzheimer's Disease

Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice
Journal of Ethnopharmacology