Early Diagnosis of Alzheimer's Disease Now Possible

Fran Lowry

June 21, 2012

June 21, 2012 (Miami Beach, Florida) — Molecular imaging with 18F-florbetaben positron emission tomography (PET) can help diagnose Alzheimer's disease when the patient first presents with symptoms and still has largely preserved mental function, researchers reported here at the SNM 2012 Annual Meeting.

"This early diagnosis should be beneficial for the patient, the family, and for society," said Christopher Rowe, MD, professor of nuclear medicine at Austin Hospital in Melbourne, Australia.

Dr. Christopher Rowe

"Previously, there was an average delay of 3 years between when a patient first went to the doctor over memory concerns and the diagnosis of Alzheimer's disease, because the diagnosis required the presence of dementia. Now, with molecular imaging used as an adjunct to other diagnostic measures, an earlier diagnosis can be made, which will give the patient several years to prepare for dementia while they still have control over their destiny," Dr. Rowe said.

Imaging Targets Toxic Protein

The imaging targets beta amyloid, a naturally occurring protein in the brain. If not cleared properly, it starts to clump and form neurotoxic plaques that eventually lead to the development of Alzheimer's disease.

"These beta amyloid plaques cause damage to the neurons that control mental functioning, including memory, language, and behavior," Dr. Rowe noted.

In their study, he and his group followed 194 elderly participants. Of these, 92 had mild cognitive impairment (MCI) and 70 had Alzheimer's disease.

Memory and hippocampal volume were assessed, and carbon-11 Pittsburgh compound B (PiB) PET brain scans were used to gauge the amyloid burden in the brain. Patients were reevaluated at 20 and 36 months.

At study entry, 74% of patients with Alzheimer's disease and 61% of patients with MCI had significantly lower hippocampal volume than the healthy control subjects. In addition, 98% of those with Alzheimer's disease, 65% of those with MCI, and 31% of healthy control subjects had high PiB.

The researchers found that widespread amyloid plaque build-up preceded cognitive impairment.

Participants with extensive amyloid burden were at high risk for cognitive decline. Over 3 years, 66% of MCI patients with a high amyloid burden progressed to Alzheimer's disease, whereas only 7% of MCI patients with a negative amyloid scan did, Dr. Rowe reported.

Additional findings showed that severe memory impairment predicted progression in MCI (relative risk [RR], 14.1; P = .0002); however, hippocampal volume did not (RR 2.3; P = .11). Progression in healthy control subjects was predicted by memory score (RR 3.4; P = .04) and hippocampal volume (RR, 2.7; P = .05).

"The implication...is that molecular imaging can help lead to diagnosis of Alzheimer's disease when the patient has only mild symptoms," Dr. Rowe said.

Dr. Rowe admitted, however, that treatments to prevent disease progression are lacking.

"Unfortunately, there is no effective treatment. At the present time, diagnosis has outstripped the development of therapies. Nevertheless, having a clear diagnosis does have benefits," he told Medscape Medical News.

The most powerful use for this type of molecular imaging will probably be to rule out Alzheimer's disease, he said.

"In those with mild memory problems who are concerned...that they might be developing Alzheimer's disease, one third of those actually are not. If you combine this scan with some other scans and with a memory assessment, you can actually be 90% certain who is not going to get Alzheimer's disease.... It is not as good if you are on the other side and you get the message that you're on the way to [Alzheimer's disease]," he said.

Sanjiv Sam Gambhir, MD, PhD, from the Virginia and D.K. Ludwig Professor of Cancer Research and chair of the Department of Radiology at Stanford University School of Medicine in California, told Medscape Medical News that "the use of 18F-florbetaben in imaging beta amyloid is showing more predictive capacity than the use of magnetic resonance imaging [MRI] to measure hippocampal volume in this large cohort with 3 years of follow-up."

Dr. Peter Herscovitch

He added that "that MRI alone is likely not going to have sufficient power; beta amyloid imaging combined with clinical assessment will be needed."

Asked for his opinion about this study, Peter Herscovitch, MD, the vice-president-elect of the Society for Nuclear Medicine, told Medscape Medical News that findings such as these will support the use of PET amyloid imaging in the design of clinical research to test new anti-amyloid and anti-Alzheimer's therapies.

"If you have a medication that is meant to clear the brain of amyloid or prevent further amyloid build-up, you obviously would like to be sure that these patients have amyloid in the brain to begin with. Using PET to enrich your population will help to successfully study the use of anti-Alzheimer's drugs," Dr. Herscovitch said.

Dr. Rowe, Dr. Gambhir, and Dr. Herscovitch have disclosed no relevant financial relationships.

SNM 2012 Annual Meeting; Scientific paper 148. Presented June 11, 2012.

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