Imaging Of Brain Chemicals Improves Alzheimers Diagnosis

The UCSF researchers, who presented their studies at the World AlzheimerCongress 2000 in Washington, DC, hope this technique might be used eventuallyto detect the degenerative disease at an earlier, more treatable stage.

The researchers used magnetic resonance spectroscopy (MRS) to detect the deathof brain cells by measuring the levels of certain chemical markers. MRS clearlyimproved the researchers' ability to distinguish patients with Alzheimer's fromthose without the disease, said Norbert Schuff, PhD, a UCSF assistant professorof radiology.

"The changes we observed are consistent with the regional patterns of damageseen in Alzheimer's disease," Schuff said. "MRS, combined with MRI, has thepotential to improve our ability to diagnose Alzheimer's, and to follow itsprogression," he added.

Schuff worked with Michael Weiner, MD, a UCSF professor of radiology,neurology, psychiatry, and medicine, and chief of the magnetic resonancespectroscopy unit at the San Francisco VA Medical Center, and othercolleagues. The team performed MRS on 41 patients with Alzheimer's disease, 11people who had been diagnosed with vascular dementia, 52 elderly people withapparently normal brain function, and 35 people who had signs of mild memoryand cognitive impairment but not dementia. They looked for decreases of thechemical N-acetyl-aspartate (NAA), a marker of healthy neurons. Theresearchers also took standard MRI measurements, which show progression ofAlzheimer's disease as a decrease in the size of certain brain lobes.

Patients with Alzheimer's disease had lower NAA levels in regions of the brainthat are damaged in the early stages of the disease, such as the hippocampusand the parietal cortex, Schuff said. When examining an unlabeled set ofpatient data, combining MRS results with standard MRI data "substantiallyimproved" their ability to identify correctly whether that patient was from theAlzheimer's group or not, he said.

Patients with vascular dementia also had a distinctive pattern of MRS resultsthat made it easier for the researchers to distinguish them from Alzheimer'spatients, and those with healthy brains, Schuff said. Although vasculardementia patients had NAA reductions in the parietal cortex similar toAlzheimer's patients, they did not share the reductions in the hippocampus, andthey had reductions in a different region, the frontal cortex, he said.

MRS may also help to identify people who are just beginning to developAlzheimer's disease, Schuff said. Patients who had mild cognitive impairmentbut not dementia, MRS results that were almost identical to Alzheimer'spatients. If later studies can show that patients like this, who havecognitive problems and a certain pattern of MRS results, are destined todevelop Alzheimer's later in life, then these patients could be selected forexperimental treatments that might stop the disease before it causes moreserious damage.

Although many clinics and hospitals in the US now have the MRI machines usedfor MRS, analysis of the data still requires the expertise of a PhD levelresearcher, Schuff said. One software company is already working on a programthat would allow interpretation of MRS data by lab technicians or other lessexperienced operators.

The promising MRS findings are important because of the limitations inherent inthe methods currently used to diagnose Alzheimer's disease, which is estimatedto affect ten percent of Americans age 65 or older. Abnormal clumps or knotsof brain cells provide ultimate proof of the disease, but they can only bediscovered during an autopsy, Schuff said. Tests of brain functions that aredamaged by the disease, such as language memory and reasoning, are onlysomewhat reliable. Genetic tests only show susceptibility to the disease, andnot the onset of the disease itself. Imaging of brain metabolism or blood flowwith PET (positron emission tomography) or another similar technique can aiddiagnosis, but requires very expensive equipment and for that reason isunavailable to most patients, he added.

Co-authors on the study were: Diane Amend and Antao Du, researchers in themagnetic resonance unit at the San Francisco VA Medical Center; William Jagust,MD, professor of medical neurology at UC Davis Medical Center; Helena Chui, MD,professor of neurology at University of Southern California; and KristineYaffe, MD, UCSF assistant professor of psychiatry.