Imaging Marker Predicts Decline to Alzheimer's

by Crystal Phend for MedPage TodayA new imaging marker for the protein plaques and tangles in the brain associated with Alzheimer's disease may act as an early warning for progressive cognitive decline, researchers found.An increase in cortical binding of the chemical marker on PET scans predicted declining memory over two years among middle-age and older adults (P=0.03 to P=0.01), Gary W. Small, MD, of the University of California Los Angeles, and colleagues reported in the February issue of the Archives of Neurology.Among individuals with mild cognitive impairment, the marker known as 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl) methylamino]-2-napthyl}ethylidene) malononitrile, or [¹⁸F]FDDNP for short, was most accurate at predicting conversion to Alzheimer's disease.Accuracy for predicting a diagnostic change from mild cognitive impairment to Alzheimer's disease was 68% for medial temporal [¹⁸F]FDDNP binding, 84% for frontal binding, 81% for parietal binding, and 88% for frontal and parietal binding.PET scans with the marker "may not only assist in predicting future cognitive decline and identifying individuals more likely to benefit from prevention treatments, but it may also track the effectiveness of such treatments to accelerate drug discovery efforts," the group suggested.Two other imaging markers have also been developed in the past decade to enable researchers to "see" evidence of Alzheimer's disease in the brain.Both carbon 11–Pittsburgh Compound B and fluorine 18-labeled florbetapir measure only amyloid plaques, though. The novel marker [¹⁸F]FDDNP is the first to measure amyloid together with neurofibrillary tau tangles.Small's group followed a cohort of 43 middle-age or older individuals without dementia at baseline who had been previously studied with the new marker.Follow-up PET imaging a median of two years later showed a mean 2.7% increase in global cortical binding of the marker among the 21 participants with mild cognitive impairment at baseline, indicating greater buildup of amyloid and tau (P<0.001).The 22 individuals studied with normal cognition didn't have significant increases in [¹⁸F]FDDNP binding over time in any area of the brain or globally.Altogether, changes in memory scores from baseline to follow-up correlated with changes in [¹⁸F]FDDNP binding globally and in the frontal cortex (both P=0.01) and in the anterior cingulate (P=0.03).This association didn't differ between the mild cognitive impairment and normal cognitive aging groups.Higher amyloid and tau levels measured by [¹⁸F]FDDNP at baseline predicted greater decline in cognitive performance in domains including executive function, language, attention and information processing speed, and visuospatial function.Alzheimer's disease was diagnosed during follow-up in six of the 21 individuals (29%) who started with mild cognitive impairment. Their baseline [¹⁸F]FDDNP binding was higher than that of the nonconverters for:

• Frontal (P=0.03)
• Parietal (P=0.04)
• Global (P=0.03)

At the optimal cutoffs, [¹⁸F]FDDNP frontal and parietal binding had a sensitivity of 100% and specificity of 67% for conversion from mild cognitive impairment to Alzheimer's disease.Medial temporal region binding had 83% sensitivity and 60% specificity for the same outcome in the mild cognitive impairment group."Thus, the pattern of [¹⁸F]FDDNP binding in mild cognitive impairment, consistent with known disease progression observed at autopsy, may provide useful information for physicians when individual patients are evaluated," Small's group concluded.In the normal aging group, two of the three participants who developed mild cognitive impairment had the highest baseline regional [¹⁸F]FDDNP binding levels seen in the group.While the numbers were too small to be definitive, this finding suggested that the marker may be promising in picking out patients at high risk for progression to mild cognitive impairment, the investigators suggested.Other limitations were the well-educated sample and binding level cutoffs optimized for the patient group studied that may not be representative of other or general populations.Source: http://www.medpagetoday.com/Neurology/Dementia/31173