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Published online before print July 8, 2009, doi:10.1212/WNL.0b013e3181b23564)
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Volume 73, Number 10, September 8, 2009
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NEUROLOGY 2009;73:754-760
© 2009 American Academy of Neurology

Conversion of amyloid positive and negative MCI to AD over 3 years

An 11C-PIB PET study

A. Okello, MRCP, J. Koivunen, BM, P. Edison, MRCP, H. A. Archer, PhD, F. E. Turkheimer, PhD, K. Någren, PhD, R. Bullock, MA, MRCPsych, Z. Walker, MD, FRCPsych, A. Kennedy, MD, N. C. Fox, MD, FRCP, M. N. Rossor, MD, FRCP, J. O. Rinne, MD, PhD and D. J. Brooks, MD, DSc

From the Division of Neuroscience and Mental Health (A.O., P.E., F.E.T., A.K., D.J.B.), Faculty of Medicine, Imperial College London, UK; Turku PET Centre (J.K., K.N., J.O.R.), University of Turku, Finland; Dementia Research Centre (H.A.A., N.C.F., M.N.R.), Department of Neurodegenerative Disease, Institute of Neurology, University College London; Kingshill Research Centre (R.B.), Victoria Hospital, Swindon; Department of Mental Health Sciences (Z.W.), University College London; and Hammersmith Imanet (D.J.B.), GE Healthcare, UK.

Address correspondence and reprint requests to Professor David J. Brooks, Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK david.brooks{at}csc.mrc.ac.uk

Background: Patients with amnestic mild cognitive impairment (MCI) represent an important clinical group as they are at increased risk of developing Alzheimer disease (AD). 11C-PIB PET is an in vivo marker of brain amyloid load.

Objective: To assess the rates of conversion of MCI to AD during a 3-year follow-up period and to compare levels of amyloid deposition between MCI converters and nonconverters.

Methods: Thirty-one subjects with MCI with baseline 11C-PIB PET, MRI, and neuropsychometry have been clinically followed up for 1 to 3 years (2.68 ± 0.6 years). Raised cortical 11C-PIB binding in subjects with MCI was detected with region of interest analysis and statistical parametric mapping.

Results: Seventeen of 31 (55%) subjects with MCI had increased 11C-PIB retention at baseline and 14 of these 17 (82%) clinically converted to AD during follow-up. Only one of the 14 PIB-negative MCI cases converted to AD. Of the PIB-positive subjects with MCI, half (47%) converted to AD within 1 year of baseline PIB PET, these faster converters having higher tracer-retention values than slower converters in the anterior cingulate (p = 0.027) and frontal cortex (p = 0.031). Seven of 17 (41%) subjects with MCI with known APOE status were {varepsilon}4 allele carriers, this genotype being associated with faster conversion rates in PIB-positive subjects with MCI (p = 0.035).

Conclusions: PIB-positive subjects with mild cognitive impairment (MCI) are significantly more likely to convert to AD than PIB-negative patients, faster converters having higher PIB retention levels at baseline than slower converters. In vivo detection of amyloid deposition in MCI with PIB PET provides useful prognostic information.

Abbreviations: AD = Alzheimer disease; ADAS = Alzheimer’s Disease Assessment Scale; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; CVLT = California Verbal Learning Test; MCI = mild cognitive impairment; MNI = Montreal Neurological Institute; PIB = Pittsburgh compound B; ROI = region of interest; SPM = statistical parametric mapping; WMS-R = Wechsler Memory Scale–Revised.


Editorial, page 744

Supplemental data at www.neurology.org

e-Pub ahead of print on July 8, 2009, at www.neurology.org.

Supported by the Medical Research Council, the Sigrid Juselius Foundation, Academy of Finland, and clinical grant of Turku University Hospital (EVO). UCLH/UCL receives funding from the NIHR Biomedical Research Centres funding scheme.

Disclosure: Author disclosures are provided at the end of the article.

Received January 25, 2009. Accepted in final form May 13, 2009.


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P. J. Visser and D. S. Knopman
Amyloid imaging in the prediction of Alzheimer-type dementia in subjects with amnestic MCI
Neurology, September 8, 2009; 73(10): 744 - 745.
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