When Senator Pete Domenici (R-New Mexico) announced last week that he had the brain degenerative disease known as frontotemporal dementia, the New York Times sought insight into the disease and the senator's prognosis from UCSF neurologist Bruce Miller, MD
Miller, a leading expert on all forms of dementia, is director of the UCSF Memory and Aging Center. He also heads a major federally funded program at UCSF known as the Alzheimer's Disease Research Center (ADRC). The ADRC designation, awarded to only a handful of academic medical research universities in the US, is designed to fuel the integration of clinical and basic research programs focused on dementia and aging.
UCSF is one of the few NIH-designated centers that focuses not only on Alzheimer's disease, but also on other forms of dementia, including frontotemporal dementia and prion diseases, including Creutzfeldt Jakob disease and new variant CJD, the human form of "mad cow" Disease.
Miller, the A.W. & Mary Margaret Clausen Distinguished Professor of Neurology, answered a few questions from his travels over the weekend.
You are a leading expert on the full range of dementias. When did you become particularly interested in frontotemporal dementia and what led to this interest?
I first became interested in FTD during my fellowship at UCLA in 1983. Soon after joining UCLA's faculty in 1985, I began to evaluate and care for a large population of patients with the disease. What fascinated me about this disorder was how it could have such a dramatic influence upon behavior and personality in previously healthy individuals. Disinhibition, repetitive compulsions, apathy, social withdrawal and loss of empathy for others were often the earliest symptoms seen, preceding deficits in memory by many years. By the same token I began to see the new emergence of creativity in patients with FTD. Hence it was a disorder that influenced and changed many of the core features of what make us uniquely human. When I started in the field there were few investigators interested in FTD and I found it exciting to try and help patient populations in whom this mysterious disease occurred.
What is the state of research on the cause of FTD and how is it diagnosed?
The past year has been the most exciting year in FTD research in my lifetime. One important advance is the ability to achieve a more accurate diagnosis of the disease. In previous decades, most patients with FTD were misdiagnosed during their life, but by obtaining brain tissue from patients with FTD we have been able to refine our diagnosis. Similarly, by studying brain tissue it has been possible to find specific proteins that accumulate in the brain and kill neurons in the frontal lobes. MRI [magnetic resonance imaging] helps with diagnosis and usually shows selective atrophy of the frontal and anterior temporal lobe regions. We are beginning to understand how focal degeneration in very specific brain regions is responsible for the behaviors that emerge in FTD.
What strategies are being pursued therapeutically?
A number of new therapies are being evaluated across the world, from the cell to the human. In 2006 investigators discovered that mutations in the gene progranulin could cause FTD. This gene produces a protein that controls cell growth and inflammation. Scientists across the world are beginning to evaluate potential therapies related to this progranulin deficiency. Similarly, abnormalities in the tau protein cause some types of FTD and tau-based therapies are also under active study. Currently, the treatments for FTD in people are relatively limited, although this is beginning to change. Adam Boxer at UCSF is directing the first placebo-controlled treatment study for FTD using a medication called memantine. Similarly, Dave Knopman at Mayo Clinics and Joel Kramer at UCSF are helping to develop a treatment trials infrastructure that should facilitate new therapies as they are developed.
Senator's Illness Requires Monitoring, Doctors Say
The New York Times
, October 7, 2007
Study Offers Window into Human Behavior, Brain Disease
UCSF News Release, December 22, 2006
UCSF Achieves Major NIH Designation for Moving in on Alzheimer's Disease and Other Dementias
UCSF News Release, June 24, 2004
Rare Cases of Dementia Stimulate Artistic Juices, Offering Unexpected Window into the Artistic Process
UCSF News Release, October 20, 1998
Frontotemporal Dementia (FTD)
UCSF Memory and Aging Center