In terms of general cognitive decline, just measuring downward change in cognition independent of Alzheimer's development, one of the cerebral spinal fluid markers - the ratio of total tau over amyloid beta - was the most useful, Landau said.

"It's kind of surprising we found this difference," she said.


When looked at individually, though, the humble pen-and-paper episodic memory test bested advanced imaging modalities as well as biochemical tests in forecasting dementia risk. Patients who performed poorly on the task were 4 times more likely to develop Alzheimer's, compared with abnormal PET scans (3 times more likely) or MRI scans (2 and a half times more likely), Landau said.

Landau suggests the reason for the slight predictive superiority of the memory test, called the Auditory Verbal Learning Test, is that it so closely resembles the sorts of tests used to actually diagnose Alzheimer's.

"Since AVLT is a paper-and-pencil cognitive test, and the diagnosis of Alzheimer's is based on the same questionnaire type of information, that could be one reason why they're related to one another," she said.

Alzheimer's is generally diagnosed by a neurologist after giving a patient a series of tests and interviewing the patient and people who know the patient well, Landau said.

Generally, a definite diagnosis can only be achieved during an autopsy, according to the National Institute on Aging.

In fact, one of the goals of Landau's research is to try to discover more objective ways to diagnose the disease while the patient is still alive.

"Officially giving someone an Alzheimer's diagnosis is kind of a subjective thing; it's not based on the kind of biological information we're looking at with the imaging scans," she said. "We'd like to have the diagnosis based on something concrete. It makes it hard to evaluate the predictive value of biomarkers when it's really hard to say this patient officially has Alzheimer's disease."

But the only problem with imaging exams, which might help for more objective diagnoses, is that they might not be cost-effective.

"From an economic point of view, the superiority of PET is challenging," write Dr. Carol Lippa, a neurologist at Drexel University, and Gael Chetelat in an editorial accompanying the article.

"It is hard to ponder health care reform in the context of biomarker studies as costly as PET," they continue. "The routine use of PET scans or other expensive diagnostics in order to obtain additional evidence to support predictions of progression or conversion may not be realistic."

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