NEUROLOGY 2009;73:2079-2085
© 2009 American Academy of Neurology
Differential association of [11C]PIB and [18F]FDDNP binding with cognitive impairment
N. Tolboom, MD,
W. M. van der Flier, PhD,
M. Yaqub, PhD,
T. Koene, MSc,
R. Boellaard, PhD,
A. D. Windhorst, PhD,
P. Scheltens, MD, PhD,
A. A. Lammertsma, PhD and
B.N.M. van Berckel, MD, PhD
From the Departments of Nuclear Medicine & PET Research (N.T., M.Y., R.B., A.D.W., A.A.L., B.N.M.v.B.), Neurology & Alzheimer Centre (N.T., W.M.v.d.F., P.S.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), and Department of Medical Psychology (T.K.), VU University Medical Centre, Amsterdam, the Netherlands.
Address correspondence and reprint requests to Dr. N. Tolboom, Department of Neurology and Alzheimer Centre, VU University Medical Centre, PO Box 7057, 1007 MB, Amsterdam, the Netherlands n.tolboom{at}vumc.nl
Objective: To evaluate associations of [11C]Pittsburgh compound B (PIB) and [18F]FDDNP with impairment in specific cognitive domains over the broader spectrum comprising cognitively normal elderly subjects, patients with mild cognitive impairment (MCI), and patients with Alzheimer disease (AD).
Methods: Twelve patients with AD, 13 patients with MCI, and 15 cognitively normal elderly subjects were included. Paired [11C]PIB and [18F]FDDNP PET scans were performed in all subjects. Binding potential (BPND) was calculated using parametric images of BPND for global, frontal, parietal, and temporal cortex; medial temporal lobe; and posterior cingulate. Cognitive functions were assessed using a battery of neuropsychological tests. Linear regression analyses were used to assess associations of [11C]PIB and [18F]FDDNP binding with cognitive measures.
Results: Adjusted for age, sex, and [18F]FDDNP binding, higher global [11C]PIB binding was associated with lower scores on the Mini-Mental State Examination, immediate and delayed recall of the Rey Auditory Verbal Learning Task (RAVLT), Visual Association Task, and Trail Making Test part B. Conversely, higher [18F]FDDNP binding was independently associated with lower scores on immediate recall of the RAVLT. After additional adjustment for diagnosis, higher [11C]PIB binding remained independently associated with delayed recall (standardized β = –0.39, p = 0.01), whereas higher [18F]FDDNP binding remained independently associated with immediate recall (standardized β = –0.32, p = 0.03). When regional binding was assessed using stepwise models, both increased frontal [11C]PIB and temporal [18F]FDDNP binding were associated with memory, whereas increased parietal [11C]PIB binding was associated with nonmemory functions.
Conclusion: Increased [18F]FDDNP binding is specifically associated with impairment of episodic memory, whereas increased [11C]Pittsburgh compound B binding is associated with impairment in a broader range of cognitive functions.
Abbreviations: Aβ = amyloid-β; AD = Alzheimer disease; BPND = binding potential; FOV = field of view; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; MR = magnetic resonance; MTL = medial temporal lobe; PIB = Pittsburgh compound B; RAVLT = Rey Auditory Verbal Learning Task; ROI = region of interest; SA = specific activity; TMT = Trail Making Test; VAT = Visual Association Task.
Supported by the Internationale Stichting Alzheimer Onderzoek (grant 05512) and the American Health Assistance Foundation (grant A2005-026).
The clinical database structure was developed with funding from Stichting Dioraphte. The Alzheimer Centre VUmc receives funding from Stichting VUmc fonds, Stichting Alzheimer Nederland, and Stichting Dioraphte.
Disclosure: Author disclosures are provided at the end of the article.
Received May 20, 2009. Accepted in final form October 6, 2009.
