News Release
March 15, 2013

Improved Detection of Frontotemporal Degeneration May Aid Clinical Trial Efforts

SAN DIEGO — A series of studies demonstrate improved detection of the second most common form of dementia, providing diagnostic specificity that clears the way for refined clinical trials testing targeted treatments. The new research is being presented by experts from the Perelman School of Medicine at the University of Pennsylvania at the American Academy of Neurology’s 65th Annual Meeting in San Diego March 16-23, 2013.

Frontotemporal degeneration, the most common dementia in people under 60, can be hereditary or sporadic in nature and caused by one of two different mutated proteins (tau or TDP-43). The disease results in damage to the anterior temporal and/or frontal lobes of the brain. As the disease progresses, it becomes increasingly difficult for people to plan or organize activities, behave appropriately in social or work settings, interact with others, and care for oneself, resulting in increasing dependency.

In one study, the team confirmed that a novel multimodal imaging approach was more accurate (88 percent) than using either MRI (72 percent) or DTI (81 percent) alone to detect FTD versus Alzheimer’s disease. The two imaging techniques integrate measures of white matter and grey matter, providing a statistically powerful method for predicting underlying pathology in order to screen patients for clinical trials.

“We are moving forward on our biomarker work to optimize our ability to identify the specific cause of an individual’s difficulties during life, said senior author Murray Grossman, MD, EdD, professor of Neurology and director of the Penn FTLD Center. “We use a novel multi-modality approach involving behavioral, imaging and biofluid biomarker measures.”

In a second study, researchers found that a brief series of neuropsychological tests of memory, word generation and conceptual flexibility (needed for creative problem-solving) helped differentiate people with very mild behavioral variant FTD (bvFTD) and those with mild cognitive impairment (MCI). The combination of tests correctly classified 85.7 percent of bvFTD cases and 83.3 percent of MCI cases at early stages of disease.

“This is particularly important because treatment trials with disease-modifying agents are emerging, often based on animal studies, yet we still don’t have all the tools we need to identify who is most appropriate to participate in one of these trials. Moreover, we can use this information we ascertain to help determine who is responding to a treatment in a clinical trial.”

The third study being presented at the meeting showed that hereditary forms of FTD appear to have more rapid cognitive decline and differing tau profiles compared with sporadic forms of the disease. For clinical trials testing whether a drug can delay damage caused by tau, any known differences in the speed of disease progression could interfere with trial results.

The studies were supported by the Wyncote Foundation, the National Institutes of Health (NS065347, AG010124, AG032953, AG017586, AG000255, NS044266, AG015116, NS053488) and a grant from the Alfonso Marti´n Escudero Foundation.

[P06.034] The Power of Multimodal Neuroimaging Biomarkers for Clinical Trial Screening
Thursday, March 21, 2013 7:30 AM

[P03.086] Utility of Neuropsychological Testing in the Differential Diagnosis of Early Behavioral Variant Frontotemporal Dementia (bvFTD) and Mild Cognitive Impairment (MCI)
Tuesday, March 19, 2013 2:00 PM

[P05.102] Longitudinal Cognitive Performance and Cerebrospinal Fluid Biomarkers in Sporadic and Hereditary Frontotemporal Lobar Degeneration
Wednesday, March 20, 2013 2:00 PM

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.

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