Skip to main content
AAN.com

Abstract

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 ε4 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.

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (okello_73-10-754.pdf)
File (table_e-1.doc)

REFERENCES

1.
Petersen RC, Parisi JE, Dickson DW, et al. Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 2006;63:665–672.
2.
Mufson EJ, Chen EY, Cochran EJ, et al. Entorhinal cortex beta-amyloid load in individuals with mild cognitive impairment. Exp Neurol 1999;158:469–490.
3.
Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985–1992.
4.
Boyle PA, Wilson RS, Aggarwal NT, et al. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology 2006;67:441–445.
5.
Tierney MC, Szalai JP, Snow WG, et al. Prediction of probable Alzheimer’s disease in memory-impaired patients: a prospective longitudinal study. Neurology 1996;46:661–665.
6.
Jack CR, Jr., Petersen RC, Xu YC, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 1999;52:1397–1403.
7.
Chetelat G, Desgranges B, de la Sayette V, Viader F, Eustache F, Baron JC. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer’s disease? Neurology 2003;60:1374–1377.
8.
Yuan Y, Gu ZX, Wei WS. Fluorodeoxyglucose-positron-emission tomography, single-photon emission tomography, and structural MR imaging for prediction of rapid conversion to Alzheimer disease in patients with mild cognitive impairment: a meta-analysis. AJNR Am J Neuroradiol Epub 2008.
9.
Bouwman FH, Schoonenboom SN, van der Flier WM, et al. CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment. Neurobiol Aging 2007;28:1070–1074.
10.
Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004;55:306–319.
11.
Forsberg A, Engler H, Almkvist O, et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 2008;29:1456–1465.
12.
Koivunen J, Pirttila T, Kemppainen N, et al. PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement Geriatr Cogn Disord 2008;26:378–383.
13.
Morris JC, Mohs RC, Rogers H, Fillenbaum G, Heyman A. Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) clinical and neuropsychological assessment of Alzheimer’s disease. Psychopharmacol Bull 1988;24:641–652.
14.
Wechsler D. Wechsler Memory Scale–Revised manual. San Antonio: The Psychological Corporation;
15.
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984;141:1356–1364.
16.
Delis DC, Kramer JH, Kaplan E, et al. California Verbal Learning Test Adult version. San Antonio: The Psychological Corporation; Harcourt Brace & Company;
17.
Becker JT, Boller F, Saxton J, McGonigle-Gibson KL. Normal rates of forgetting of verbal and non-verbal material in Alzheimer’s disease. Cortex 1987;23:59–72.
18.
Okello A, Edison P, Archer HA, et al. Microglial activation and amyloid deposition in mild cognitive impairment. Neurology 2009;72:56–62.
19.
Kemppainen NM, Aalto S, Wilson IA, et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 2007;68:1603–1606.
20.
Edison P, Archer HA, Hinz R, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 2007;68:501–508.
21.
Edison P, Rowe CC, Rinne JO, et al. Amyloid load in Parkinson’s disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry 2008;79:1331–1338.
22.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
23.
Brix G, Zaers J, Adam LE, et al. Performance evaluation of a whole-body PET scanner using the NEMA protocol: National Electrical Manufacturers Association. J Nucl Med 1997;38:1614–1623.
24.
Kemppainen NM, Aalto S, Wilson IA, et al. Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology 2006;67:1575–1580.
25.
Hammers A, Allom R, Koepp MJ, et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 2003;19:224–247.
26.
Turkheimer FE, Smith CB, Schmidt K. Estimation of the number of “true” null hypotheses in multivariate analysis of neuroimaging data. Neuroimage 2001;13:920–930.
27.
Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology 2007;68:1718–1725.
28.
Price JC, Klunk WE, Lopresti BJ, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 2005;25:1528–1547.
29.
Larrieu S, Letenneur L, Orgogozo J, et al. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology 2002;59:1594–1599.
30.
Klunk WE, Price JC, Mathis CA, et al. Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci 2007;27:6174–6184.
31.
Koivunen J, Verkkoniemi A, Aalto S, et al. PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer’s disease. Brain 2008;131:1845–1853.
32.
Remes AM, Laru L, Tuominen H, et al. Carbon 11-labeled Pittsburgh compound B positron emission tomographic amyloid imaging in patients with APP locus duplication. Arch Neurol 2008;65:540–544.
33.
Engler H, Forsberg A, Almkvist O, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006;129:2856–2866.
34.
Kemppainen NM, Aalto S, Karrasch M, et al. Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol 2008;63:112–118.
35.
Schmechel DE, Saunders AM, Strittmatter WJ, et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993;90:9649–9653.
36.
Rebeck GW, Reiter JS, Strickland DK, Hyman BT. Apolipoprotein E in sporadic Alzheimer’s disease: allelic variation and receptor interactions. Neuron 1993;11:575–580.
37.
Polvikoski T, Sulkava R, Haltia M, et al. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. N Engl J Med 1995;333:1242–1247.
38.
Grimmer T, Henriksen G, Wester HJ, et al. Clinical severity of Alzheimer’s disease is associated with PIB uptake in PET. Neurobiol Aging Epub 2008.
39.
Pike K, Savage G, Villemagne V, et al. β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 2007;130:2837–2844.
40.
Mintun MA, Larossa GN, Sheline YI, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 2006;67:446–452.

Information & Authors

Information

Published In

Neurology®
Volume 73Number 10September 8, 2009
Pages: 754-760
PubMed: 19587325

Publication History

Published online: July 8, 2009
Published in print: September 8, 2009

Permissions

Request permissions for this article.

Notes

Authors

Affiliations & Disclosures

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

Notes

Address correspondence and reprint requests to Professor David J. Brooks, Cyclotron Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [email protected]

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Image processing: an early detection tool for Alzheimer’s disease, Smart Diagnostics for Neurodegenerative Disorders, (99-136), (2024).https://doi.org/10.1016/B978-0-323-95539-3.00001-6
    Crossref
  2. Altered Feedback-Related Negativity in Mild Cognitive Impairment, Brain Sciences, 13, 2, (203), (2023).https://doi.org/10.3390/brainsci13020203
    Crossref
  3. Advances in diagnosing mild cognitive impairment and Alzheimer’s disease using 11C-PIB- PET/CT and common neuropsychological tests, Frontiers in Neuroscience, 17, (2023).https://doi.org/10.3389/fnins.2023.1216215
    Crossref
  4. Prediction of Amyloid β-Positivity with both MRI Parameters and Cognitive Function Using Machine Learning, Journal of the Korean Society of Radiology, 84, 3, (638), (2023).https://doi.org/10.3348/jksr.2022.0084
    Crossref
  5. Cognitive Trajectories and Associated Biomarkers in Patients with Mild Cognitive Impairment, Journal of Alzheimer's Disease, 92, 3, (803-814), (2023).https://doi.org/10.3233/JAD-220326
    Crossref
  6. Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment, Journal of Nanobiotechnology, 21, 1, (2023).https://doi.org/10.1186/s12951-023-01793-7
    Crossref
  7. Heart rate variability and risk of agitation in Alzheimer’s disease: the Atherosclerosis Risk in Communities Study, Brain Communications, 5, 6, (2023).https://doi.org/10.1093/braincomms/fcad269
    Crossref
  8. Learning potential and visuospatial memory could predict amyloid-beta positron emission tomography positivity in amnestic mild cognitive impairment, Psychiatry Research: Neuroimaging, 335, (111705), (2023).https://doi.org/10.1016/j.pscychresns.2023.111705
    Crossref
  9. Deep learning-based classification of healthy aging controls, mild cognitive impairment and Alzheimer’s disease using fusion of MRI-PET imaging, Biomedical Signal Processing and Control, 80, (104312), (2023).https://doi.org/10.1016/j.bspc.2022.104312
    Crossref
  10. Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer’s disease, Aging Clinical and Experimental Research, 35, 8, (1741-1752), (2023).https://doi.org/10.1007/s40520-023-02452-5
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share