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EARLY-ONSET DEMENTIA IS OFTEN DUE TO PREVENTABLE CAUSES — AND PET HELPS DIAGNOSIS

SAN DIEGO—The clinical history and PET may be useful in the evaluation of patients with early-onset dementia – dementia that strikes before age 65 years, two new studies presented here at the American Neurological Association (ANA) Annual Meeting suggest.

The first study showed that patients who develop dementia before age 65 years have more preventable conditions, including cognitive deficits and impaired functioning attributed to head trauma, alcohol abuse, and HIV, than do patients with later-onset dementia.

A second study showed that [18F] fluorodeoxyglucose PET (FDG-PET) can help distinguish between progressive dementia and cognitive impairment of unknown etiology in younger patients.

Aaron M. McMurtray, MD, a Neurobehavioral Fellow in the Department of Neurology at the University of California-Los Angeles and lead investigator of both studies, told Neurology Today that “it's important to alert clinicians to the fact that younger patients with dementia are likely to have preventable causes for their conditions.

“What causes dementia in older patients is much different from what causes dementia in younger patients. In the young, many of the causes are preventable. If you get a patient with early-onset dementia, ask about alcohol abuse and history of traumatic brain injury,” he advised.

STUDY DESIGN

The study, which has garnered an ANA fellowship travel award, was designed to investigate the frequency and causes of early-onset dementia versus late-onset dementia at a Veterans Affairs memory program over a four-year period. Dementia was diagnosed if patients had deficits in two or more domains of cognition sufficient to impair social or occupational functioning and implied a significant decline from previous levels of functioning.

Of 1,683 patients who were evaluated, 948 (56.3 percent) met these criteria for dementia; 278 (29.3 percent) became demented before age 65 years, at a mean age of 51, and 670 (70.7 percent) had symptom-onset at age 65 years or older.

Alcohol abuse accounted for 5 percent of cases of early-onset dementia compared to only 3 percent of late-onset. Traumatic brain injury accounted for 24 percent of early-onset dementia versus 4 percent of late-onset dementia. HIV accounted for 8 percent of early-onset dementia versus 3 percent of late-onset dementia. And frontotemporal dementia (FTD) accounted for 3 percent of cases of early-onset dementia versus less than 1 percent of late-onset dementia. All the differences reached statistical significance, Dr. McMurtray said.

In contrast, Alzheimer disease accounted for 52 percent of cases of late-onset dementia and only 17 percent of those with early-onset, he said.

CONFIRMATION OF CLINICAL OBSERVATIONS

Lawrence S. Honig, MD, PhD, Associate Professor of Clinical Neurology in the Gertrude H. Sergievsky Center, the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and in the Department of Neurology, Division of Dementia and Aging, at Columbia University in New York City, said that the findings confirm what is generally seen in clinical practice.

“While it depends on the referring physician, overall, we see much more Alzheimer disease in older patients and dementia due to preventable causes such as traumatic brain injury and alcohol abuse in younger patients,” he said.

Stephen Salloway, MD, Director of Neurology and The Memory and Aging Program at Butler Hospital and Professor of Clinical Neurosciences and Psychiatry at Brown Medical School in Providence, RI, agreed.

“If you go to an HIV clinic, you will see HIV-related dementia,” he said. “In the memory clinic, we do see younger patients with dementia and some may turn out to have Alzheimer disease. But generally you don't really see that much Alzheimer disease in people under 50.”

Dr. McMurtray said that while the researchers were expecting Alzheimer disease to be less prevalent in younger persons, they were surprised at their high rates of dementia due to alcohol abuse, traumatic brain injury, and HIV.

The findings will be even more important as new treatments for traumatic brain injury, alcohol abuse, and other causes of early-onset dementia are developed, he added.

In addition to noting age at symptom-onset to uncover preventable causes of dementia, clinicians might consider PET for younger patients with memory loss, Dr. McMurtray said.

While previous studies have shown that PET is useful for identifying dementia in elderly patients (J Nucl Med 2002;43:253-266; JAMA 2001;286:2120-2127), he said that the new study extends the findings to people younger than 65 years.

DETECTION OF DEMENTIA IN THOSE YOUNGER THAN 65

“We wanted to see if PET is just as useful in younger people and it was. PET should be used routinely in the younger patient, just as it is in the 65-plus crowd. The technique decreases false-positive diagnoses of Alzheimer disease or other specific dementia on initial presentation,” he said.

The study showed that FDG-PET had a sensitivity of 62.5 percent in detecting any dementia, a sensitivity of 95 percent in detecting Alzheimer disease, and a sensitivity of 96.2 percent of those with cognitive impairment but not dementia.

The study included 58 subjects younger than age 65 who came to a Veterans Affairs memory disorders center. All were screened for treatable causes of cognitive impairment, including vitamin B12 deficiency, thyroid function abnormalities, neurosyphilis, and normal pressure hydrocephalus.

All participants had PET within three months of the first clinical evaluation and the images were re-read by two neurologists blinded to the clinical diagnosis.

The researchers then compared the presence of cortical hypometabolism on PET imaging to the clinical diagnosis established over a follow-up period.

Of the 58 patients not yet meeting criteria for dementia at first, 32 progressed to dementia by the time of the follow-up study three months later and 22 were diagnosed with Alzheimer disease. The other 26 participants with cognitive impairment had not become demented.

The temporoparietal hypometabolism on PET correlated well with the clinical diagnosis of Alzheimer disease at the end of the follow-up period, although is did not correlate well with other causes of dementia, Dr. McMurtray said.

“One possible explanation is that disorders like Alzheimer disease, which affect cortical metabolism early in the disease course, may be easier for PET to detect, while disorders like HIV-associated dementia which do not affect cortical metabolism early on would be harder for PET to detect,” he said.

Dr. Salloway said the findings add to growing evidence that metabolic PET imaging may have benefit in the diagnosis of the earliest stages of Alzheimer disease. “It may help to find cognitive changes even before the patient has any symptoms,” he said.

The big problem with using PET for determining onset of dementia, Dr. Salloway said, is the issue of cost. Each scan costs about $3,000 and Medicare has approved PET only for the differential diagnosis of atypical dementia, he said. Coverage for PET will become even more important as treatments that slow the progression of AD are developed, Dr. Salloway said. “Once that happens, a PET for early diagnosis of dementia will be analogous to getting a mammogram for breast cancer,” he said.

ARTICLE IN BRIEF

  • ✓ New studies identify factors that contribute to early-onset dementia and the role that PET and SPECT can play in predicting its development.