Prediction of Cognitive decline via PET of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome

Positron Emission Tomography of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome

Science daily article

Dr. Linda D. Nelson, PhD, Dr. Prabha Siddarth, PhD, Dr. Vladimir Kepe, PhD, Mr. Kevin E. Scheibel, BS, Dr. S. C. Huang, PhD, Dr. Jorge R. Barrio, PhD, and Dr. Gary W. Small, MD

Departments of Psychiatry and Biobehavioral Sciences (Drs Nelson, Siddarth, and Small), Molecular and Medical Pharmacology (Drs Kepe, Huang, and Barrio), and Neurology (Mr Scheibel), Semel Institute for Neuroscience and Human Behavior (Drs Nelson, Siddarth, and Small), Brain Research Institute (Dr Nelson), UCLA Intellectual and Developmental Disabilities Research Center (Dr Nelson), Mary S. Easton Center for Alzheimer’s Disease Research (Drs Kepe and Small), and UCLA Center on Aging (Dr Small), University of California, Los Angeles

strong>ABSTRACT

Objectives
To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18–labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([18F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [18F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants.
Design
Cross-sectional clinical study.
Participants
Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years).
Main Outcome Measures
Binding of [18F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding).
Results
The [18F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [18F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [18F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [18F]FDDNP binding.
Conclusions
Consistent with neuropathological findings from postmortem studies, [18F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [18F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer-type neuropathological findings in this population.

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