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Imaging Alzheimer Pathology in Mild Cognitive Impairment

A new imaging technique shows promise in distinguishing MCI and AD from normal aging.

Early diagnosis of Alzheimer disease (AD) is critical for finding a successful disease-modifying therapy. Several imaging markers have shown promise in identifying individuals at risk for AD. Now, researchers have tested the ability of using FDDNP, a positron emission tomography (PET) radiotracer that binds to amyloid plaques and neurofibrillary tangles, to differentiate early AD from normal aging. At baseline, 83 adults (age range, 49–84) underwent imaging and neuropsychological testing; 12 had follow-up imaging and testing about 2 years later.

The 28 subjects with mild cognitive impairment (MCI) had significantly more FDDNP binding than did the 30 normal controls and significantly less FDDNP binding than did the 25 patients with clinical AD. FDDNP-PET seemed to differentiate the three groups better than did either volumetric MRI or FDG-PET (another PET imaging method that measures glucose metabolism).

Higher levels of FDDNP binding correlated significantly with worse performance on cognitive tests. A small subset of subjects had repeat FDDNP-PET imaging after approximately 2 years, and three subjects who had evidence of clinical worsening showed increased FDDNP binding at follow-up.

Comment: These findings add to a growing literature that supports PET imaging of AD pathology as a potential tool in early diagnosis and in assessment of promising therapies for AD. Several studies of Pittsburgh Compound B, a PET agent that primarily binds fibrillar amyloid, have had similar findings. One potential issue in the current study was the relatively large number of individuals who underwent FDDNP-PET imaging but were excluded from analysis because they did not complete the neuropsychological testing or had poor-quality FDDNP-PET data due to head motion. Longitudinal studies of individuals with MCI are underway to determine whether PET amyloid imaging can accurately predict which subjects will progress to clinical AD.

— Reisa Sperling, MD, MMSc

Dr. Sperling is Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital, Boston.

Published in Journal Watch Neurology March 27, 2007

Citation(s):

Small GW et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med 2006 Dec 21; 355:2652-63.

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