Chemical Marker that Binds to Brain Deposits May Help Identify Persons At-Risk For Future Cognitive Decline



Increases in brain cortical binding of the chemical marker called [18F]FDDNP were associated with increases in clinical symptoms of neurodegeneration, and regional baseline values of this marker appear to be associated with future cognitive decline, according to a report in the February issue of Archives of Neurology, one of the JAMA/Archives journals.

“Nearly 20 percent of people 65 years or older have mild cognitive impairment (MCI), and 10 percent have dementia. Such a high prevalence has led to recent research on the development of brain imaging tools to track the neuropathologic changes associated with these conditions,” the authors write as background information. “Previous cross-sectional studies have shown that [18F]FDDNP brain binding patterns correspond to the known neuropathologic deposition patterns determined from autopsy studies.”

To assess whether [18F]FDDNP brain regional binding values increase as cognitive decline progresses and whether baseline [18F]FDDNP binding values are predictors of future cognitive decline, Gary W. Small, M.D., and colleagues with the David Geffen School of Medicine at the University of California, Los Angeles, evaluated a volunteer sample of 43 middle-age and older persons (median age 64 years; range 40 to 87 years), which included 21 patients with mild cognitive impairment (MCI) and 22 patients with normal aging. The authors measured longitudinal [18F]FDDNP positron emission tomography (PET) binding values in specific areas of the brain among patients in each group (MCI vs. normal aging).

At the two-year follow up, patients in the MCI group showed significant increases in [18F]FDDNP binding values in frontal, parietal, posterior cingulate, and global regions, but levels in the medial temporal region did not increase significantly. The normal aging group did not show significant binding increases in any region. Also, among patients in the MCI group, frontal and parietal [18F]FDDNP binding showed the greatest diagnostic accuracy in identifying patients at highest risk of converting to Alzheimer disease compared with those who were not at risk of converting after two years.

The authors also found that among the entire study group, increases in frontal, posterior cingulate, and global binding at follow-up were associated with progression of memory decline after two years. Higher [18F]FDDNP binding at baseline was also associated with future decline in most cognitive domains including language, attention, executive, and visuospatial abilities.

“Our findings indicate that in vivo regional [18F]FDDNP binding patterns are consistent with known patterns of disease deposition and associated with future disease course,” the authors conclude. “Using [18F]FDDNP PET 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.”

(Arch Neurol. 2012;69[2]:215-222.