Amyloid Imaging May Help Detect High Risk for Conversion From MCI to Alzheimer’s Disease



PHILADELPHIA—An amyloid PET scan with florbetapir detected which patients with mild cognitive impairment (MCI) had a high risk for further cognitive decline to Alzheimer’s disease in a large analysis of patients presented at the Clinical Trials Conference on Alzheimer’s Disease.

Participants in the Alzheimer’s Disease Neuroimaging Initiative who tested positive for amyloid on florbetapir (Amyvid) PET scan at baseline were five times more likely to convert to Alzheimer’s dementia within three years than were amyloid-negative subjects, according to data from the large, multisite imaging registry.

The finding suggests that amyloid imaging could help rule out Alzheimer’s disease as the underlying cause of cognitive problems, allowing physicians to focus more closely on other potential diagnoses, said Mr. Ming Lu, lead statistician at Avid Radiopharmaceuticals, a subsidiary of Eli Lilly, which markets florbetapir and sponsored the study.

“This study supports the hypothesis that amyloid PET scans are able to detect those levels of Alzheimer’s disease pathology that are associated with risk of cognitive decline, even in subjects that are not showing evidence of dementia,” Mr. Lu said. “It also underscores the potential importance of diagnosing the cause of someone’s cognitive decline earlier rather than later, as this may provide useful information for a physician’s management or treatment plan for these patients.”

Similar findings have been noted in smaller studies. The Alzheimer’s Disease Neuroimaging Initiative, comprising 478 subjects, is the largest prospective study to date to look at the issue.

On PET imaging, florbetapir binds to amyloid plaques, a pathophysiologic hallmark of Alzheimer’s disease. So far, the agent is used only in studies of patients with diagnosed MCI or Alzheimer’s disease, and patients are limited to one scan. It is not covered by Medicare in clinical use.

Patients in the Alzheimer’s Disease Neuroimaging Initiative study had a mean age of 72, but ranged from 48 to 91. All participants had undergone at least one florbetapir scan as well as extensive cognitive testing with a variety of instruments, including the Mini-Mental State Examination (MMSE), the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

On imaging, 212 patients were amyloid negative and 266 were amyloid positive. Over a three-year follow-up period, amyloid-positive patients declined a mean of 4.03 points on the ADAS-cog, compared with 0.26 points for amyloid-negative patients. Amyloid-positive patients declined 2.61 points on the MMSE, compared with 0.40 in the negative patients, and on the CDR-SB, the change was 1.53 versus –0.11 points. All of these changes were statistically significant, Mr. Lu reported.

Declines of this magnitude would correlate with significant clinical changes, Mr. Lu noted. Compared with the amyloid-negative patients, the amyloid-positive patients had a twofold higher risk to progress to a clinically significant change (ie, an ADAS-cog score decline of 4 points or more), and nearly a fivefold higher risk of conversion to Alzheimer’s disease.

Michele G. Sullivan

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