Senator Domenici Has Rare Dementia, Frontotemporal Lobar Degeneration

WASHINGTON, Oct. 4 -- Senator Pete Domenici (R, N.M.), is expected to announce today that he has been diagnosed with frontotemporal lobar degeneration, and will not seek re-election when his sixth term expires in 2008.

Frontotemporal lobar degeneration is one of the disorders under the broader category of frontotemporal dementias. Unlike Alzheimer's disease, which most commonly occurs after age 65, frontotemporal dementias may affect adults as young as 35, and because younger patients tend to be in better physical health, their post-diagnosis survival may be up to 10 years. Domenici is 75.

In an interview, John C. Morris, M.D., a professor of neurology at Washington University in St. Louis, said "frontotemporal dementia is an umbrella term for a number of distinct illnesses that have the same ultimate pathway -- that is, they cause nerve cell death in the frontal and temporal lobes."

There are two classic presentations of frontotemporal dementias, noted David Knopman, M.D., a professor of neurology at the Mayo Clinic in Rochester, Minn., one involving personality and behavioral changes, and the other involving speech disturbances.

"In behavioral variant frontotemporal dementia, there are major changes in personality," Dr. Knopman said in an interview. "People become either very quiet and apathetic, or they become disinhibited, impulsive, and socially inappropriate."

In more severe cases the lack of inhibition can lead to public behaviors that are acutely embarrassing to family and friends, and the patient's behavioral changes cause severe disruption in relationships. In addition, patients may develop cognitive problems including difficulty reasoning, impaired mental agility, and difficulty solving problems.

A second classic presentation of the disorder is disturbance in expressive speech, with loss of fluency and ability to communicate well with others. In some patients the behavioral and speech presentations may be mixed, depending on the brain region involved, Dr. Morris said.

According to the National Institute on Aging, distinguishing frontotemporal dementias from Alzheimer's disease is crucial, because some agents used to treat the latter, such as cholinesterase inhibitors, may be harmful or ineffective in patients with frontotemporal dementias.

Diagnosis generally involves a careful medical history with focus on behavioral changes reported by family members and others close to the patient; neuropsychological assessments of language, memory, executive functioning, and visual-spatial skills; and neuroimaging to determine the extent of atrophy.

There are no therapies that can either slow or halt the progress of frontotemporal dementia, although atypical antipsychotic agents targeted toward specific undesirable behaviors may make those behaviors more manageable, Dr. Knopman said.

Practical strategies for managing the disorders include keeping the patient from driving, making financial decisions, or from any situations in which judgment and reasoning are important. Full-time nursing facilities may be required for patients in advanced stages of disease.

Frontotemporal degenerative disorders have a stronger genetic component than Alzheimer's disease, with familial forms accounting for about 25% of all cases, Dr. Knopman said.

At least three key genetic mutations have been identified. One set of mutations involves genes encoding for tau, a protein found in neurofibrillary tangles both in some forms of frontotemporal dementias and in Alzheimer's disease. More recently, two other proteins have been identified: progranulin, a growth factor, and TDP-43, a cellular protein implicated in both frontotemporal dementias and amyotrophic lateral sclerosis. The gene encoding for familial frontotemporal lobar degenerations has yet to be identified, Dr. Knopman noted.

Although the pathologic changes vary, they may include accumulation of abnormal tau in neurons, leading to disruption of neuronal processes and apoptosis, progressive of loss of frontal and temporal neurons, gliosis and vacuolation. Amyloid deposits, a hallmark of Alzheimer's disease, are not typically seen in frontotemporal dementias, however.