Imaging of Brain Chemicals Improves Alzheimers Diagnosis

By Kevin Boyd

Diagnosing Alzheimer’s disease may become easier with the help of imaging studies from the San Francisco Veteran’s Affairs Medical Center, which is affiliated with UC San Francisco.  Using a variation on MRI (magnetic resonance imaging), the researchers report they can differentiate between Alzheimer’s patients and healthy people, and between Alzheimer’s and vascular dementia, a disease with similar symptoms.

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

The researchers used magnetic resonance spectroscopy (MRS) to detect the death of brain cells by measuring the levels of certain chemical markers. MRS clearly improved the researchers’ ability to distinguish patients with Alzheimer’s from those without the disease, said Norbert Schuff, PhD, a UCSF assistant professor of radiology.

“The changes we observed are consistent with the regional patterns of damage seen in Alzheimer’s disease,” Schuff said.  “MRS, combined with MRI, has the potential to improve our ability to diagnose Alzheimer’s, and to follow its progression,” he added.

Schuff worked with Michael Weiner, MD, a UCSF professor of radiology, neurology, psychiatry, and medicine, and chief of the magnetic resonance spectroscopy unit at the San Francisco VA Medical Center, and other colleagues.  The team performed MRS on 41 patients with Alzheimer’s disease, 11 people who had been diagnosed with vascular dementia, 52 elderly people with apparently normal brain function, and 35 people who had signs of mild memory and cognitive impairment but not dementia.  They looked for decreases of the chemical N-acetyl-aspartate (NAA), a marker of healthy neurons.  The researchers also took standard MRI measurements, which show progression of Alzheimer’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 brain that are damaged in the early stages of the disease, such as the hippocampus and the parietal cortex, Schuff said.  When examining an unlabeled set of patient data, combining MRS results with standard MRI data “substantially improved” their ability to identify correctly whether that patient was from the Alzheimer’s group or not, he said.

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

MRS may also help to identify people who are just beginning to develop Alzheimer’s disease, Schuff said.  Patients who had mild cognitive impairment but not dementia, MRS results that were almost identical to Alzheimer’s patients.  If later studies can show that patients like this, who have cognitive problems and a certain pattern of MRS results, are destined to develop Alzheimer’s later in life, then these patients could be selected for experimental treatments that might stop the disease before it causes more serious damage. 

Although many clinics and hospitals in the US now have the MRI machines used for MRS, analysis of the data still requires the expertise of a PhD level researcher, Schuff said.  One software company is already working on a program that would allow interpretation of MRS data by lab technicians or other less experienced operators.

The promising MRS findings are important because of the limitations inherent in the methods currently used to diagnose Alzheimer’s disease, which is estimated to affect ten percent of Americans age 65 or older.  Abnormal clumps or knots of brain cells provide ultimate proof of the disease, but they can only be discovered during an autopsy, Schuff said.  Tests of brain functions that are damaged by the disease, such as language memory and reasoning, are only somewhat reliable.  Genetic tests only show susceptibility to the disease, and not the onset of the disease itself.  Imaging of brain metabolism or blood flow with PET (positron emission tomography) or another similar technique can aid diagnosis, but requires very expensive equipment and for that reason is unavailable to most patients, he added.

Co-authors on the study were: Diane Amend and Antao Du, researchers in the magnetic 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 Kristine Yaffe, MD, UCSF assistant professor of psychiatry.