St. Louis, March 5, 1998 -- Alzheimer's disease can be clinically diagnosed about two years earlier than is generally thought, according to a large study of aging people. The research shows that even very mild forms of the disorder can be distinguished from the memory changes that occur with normal aging.
There are several reasons why early diagnosis is important, says lead researcher Leonard Berg, M.D., professor of neurology at Washington University School of Medicine in St. Louis. "First, it provides an opportunity to prescribe medications that can help with symptoms," he says. "Second, there are several reversible medical conditions, such as hypothyroidism and depression, that can produce Alzheimer-like symptoms. Third, people ought to know they have Alzheimer's disease while they're still able to make decisions about future care."
The study, described in the March issue of Archives of Neurology, involved 224 patients, some of whom had been followed for as long as 16 years. When they died, they were between 46 and 106 years of age. Each patient was examined yearly and classified as having Alzheimer's or being cognitively healthy. The diagnoses were based on videotaped interviews with patients, relatives and friends. The patients were rated on memory, orientation, judgment and problem solving, cognitive functioning at home and in the community, and ability to undertake personal care.
After each participant died, a pathologist autopsied the brain. Alzheimer's was confirmed if the brain contained plaques of a protein called beta-amyloid and tangled nerve cells called neurofibrillary tangles.
The autopsy results confirmed 93 percent of the 207 positive diagnoses, including those of 17 people in the very mild stage of the disease. One of them was an 83-year-old man who had hired an accountant to file his tax return when he had always filed the return himself. Another patient hadn't remembered how to get to the highway, and a third had had trouble filling out bank deposit slips.
"So something is changing," Berg says. "The person is having a little more difficulty getting things done. There also may be changes in other intellectual functions, such as coming up with words or performing calculations."
The 7 percent of patients who proved not to have Alzheimer's disease turned out to have rare degenerative diseases of the brain that also can produce dementia. The lack of pathology in 13 brains confirmed the cognitively healthy diagnoses. One person with a normal brain was mistakenly diagnosed with very mild Alzheimer's, however.
The study showed that the brains of patients with even very mild Alzheimer's are choked with amyloid plaque. "It is our notion that amyloid deposition is one of the early features of the disease," Berg says. "The number of neurofibrillary tangles, on the other hand, was more closely related to the severity of dementia."
Berg says the average family physician could diagnose mild Alzheimer's by taking more time to take a complete history from patients and their loved ones. The mental status questionnaires that physicians use at present are useful only when the disease is fairly advanced, he says.
"We're saying, 'Listen up, people. Our autopsy findings present substantial new evidence that Alzheimer's disease can be clinically diagnosed even at the very mild stage, when the disease does not interfere substantially with everyday activities,'" Berg says. "Any experienced physician who takes the time could detect these changes -- whether or not patients recognize that something's amiss."
The study was funded by four grants from the National Institute on Aging and a grant from Metropolitan Life Foundation.
Berg L, McKeel DW, Miller JP, Storandt M, Rubin EH, Morris JC, Baty J, Coats M, Norton J, Goate AM, Price JL, Gearing M, Mirra SS, Saunders AM. Clinicopathologic Studies in Cognitively Healthy Aging and Alzheimer's Disease: Relation of Histologic Markers to Dementia Severity, Age, Sex, and ApoE Genotype. Archives of Neurology, 55, 326-335, March 1998.
Journal
Archives of Neurology