• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (149)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Aging/ Geriatrics  • Neurology  • Alzheimer Disease  • Dementias  • Alert me on articles by topic  Social Bookmarking   What's this?

Howard Jay Aizenstein, MD, PhD; Robert D. Nebes, PhD; Judith A. Saxton, PhD; Julie C. Price, PhD; Chester A. Mathis, PhD; Nicholas D. Tsopelas, MD; Scott K. Ziolko, MS; Jeffrey A. James, BS; Beth E. Snitz, PhD; Patricia R. Houck, MS; Wenzhu Bi, MS; Ann D. Cohen, PhD; Brian J. Lopresti, BS; Steven T. DeKosky, MD; Edythe M. Halligan, MA; William E. Klunk, MD, PhD

Arch Neurol. 2008;65(11):1509-1517.

Objective  To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests.

Design  Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs).

Setting  University medical center.

Participants  From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included.

Main Outcome Measures  Regional PiB retention and cognitive test performance.

Results  Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants.

Conclusions  Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

Author Affiliations: Departments of Psychiatry (Drs Aizenstein, Nebes, Tsopelas, Cohen, and Klunk and Mss Houck and Halligan), Neurology (Drs Saxton, Snitz, DeKosky, and Klunk), and Radiology (Drs Price and Mathis and Messrs Ziolko, James, Bi, and Lopresti), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

This Month in Archives of Neurology
Arch Neurol. 2008;65(11):1415-1416.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

{beta}-Amyloid burden in healthy aging: Regional distribution and cognitive consequences
Rodrigue et al.
Neurology 2012;78:387-395.
ABSTRACT | FULL TEXT  

APOE modifies the association between A{beta} load and cognition in cognitively normal older adults
Kantarci et al.
Neurology 2012;78:232-240.
ABSTRACT | FULL TEXT  

Association of Lifetime Cognitive Engagement and Low {beta}-Amyloid Deposition
Landau et al.
Arch Neurol 2012;0:archneurol.2011.2748v1-7.
ABSTRACT | FULL TEXT  

Effectiveness and Safety of 18F-FDG PET in the Evaluation of Dementia: A Review of the Recent Literature
Bohnen et al.
JNM 2012;53:59-71.
ABSTRACT | FULL TEXT  

Blood-brain barrier P-glycoprotein function in Alzheimer's disease
van Assema et al.
Brain 2012;135:181-189.
ABSTRACT | FULL TEXT  

Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD
Rabinovici et al.
Neurology 2011;77:2034-2042.
ABSTRACT | FULL TEXT  

Brain Amyloid Imaging
Rowe and Villemagne
JNM 2011;52:1733-1740.
ABSTRACT | FULL TEXT  

Using Positron Emission Tomography and Florbetapir F 18 to Image Cortical Amyloid in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer Disease
Fleisher et al.
Arch Neurol 2011;68:1404-1411.
ABSTRACT | FULL TEXT  

CSF Biomarker and PIB-PET-Derived Beta-Amyloid Signature Predicts Metabolic, Gray Matter, and Cognitive Changes in Nondemented Subjects
Ewers et al.
Cereb Cortex 2011;0:bhr271v1-bhr271.
ABSTRACT | FULL TEXT  

Chromatin plasticity and the pathogenesis of Huntington disease
Ehrlich and Gandy
Proc. Natl. Acad. Sci. USA 2011;108:16867-16868.
FULL TEXT  

Subtypes of progressive aphasia: application of the international consensus criteria and validation using {beta}-amyloid imaging
Leyton et al.
Brain 2011;134:3030-3043.
ABSTRACT | FULL TEXT  

Magnetic resonance spectroscopy, {beta}-amyloid load, and cognition in a population-based sample of cognitively normal older adults
Kantarci et al.
Neurology 2011;77:951-958.
ABSTRACT | FULL TEXT  

Early detection of Alzheimer disease: 11C-PiB PET in twins discordant for cognitive impairment
Scheinin et al.
Neurology 2011;77:453-460.
ABSTRACT | FULL TEXT  

Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology
O'Brien et al.
J Psychopharmacol 2011;25:997-1019.
ABSTRACT | FULL TEXT  

Ecology of the Aging Human Brain
Sonnen et al.
Arch Neurol 2011;68:1049-1056.
ABSTRACT | FULL TEXT  

Amyloid Imaging with 18F-Florbetaben in Alzheimer Disease and Other Dementias
Villemagne et al.
JNM 2011;52:1210-1217.
ABSTRACT | FULL TEXT  

Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology
Hedden et al.
Cereb Cortex 2011;0:bhr172v1-bhr172.
ABSTRACT | FULL TEXT  

Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease
Ikonomovic et al.
Neurology 2011;77:39-47.
ABSTRACT | FULL TEXT  

Longitudinal Patterns of {beta}-Amyloid Deposition in Nondemented Older Adults
Sojkova et al.
Arch Neurol 2011;68:644-649.
ABSTRACT | FULL TEXT  

Cognitive reserve and Alzheimer's disease biomarkers are independent determinants of cognition
Vemuri et al.
Brain 2011;134:1479-1492.
ABSTRACT | FULL TEXT  

Spatial patterns of brain amyloid-{beta} burden and atrophy rate associations in mild cognitive impairment
Tosun et al.
Brain 2011;134:1077-1088.
ABSTRACT | FULL TEXT  

In Vivo Fibrillar {beta}-Amyloid Detected Using [11C]PiB Positron Emission Tomography and Neuropathologic Assessment in Older Adults
Sojkova et al.
Arch Neurol 2011;68:232-240.
ABSTRACT | FULL TEXT  

Carbon-11-Pittsburgh compound B positron emission tomography imaging of amyloid deposition in presenilin 1 mutation carriers
Knight et al.
Brain 2011;134:293-300.
ABSTRACT | FULL TEXT  

Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease
Jack et al.
Brain 2010;133:3336-3348.
ABSTRACT | FULL TEXT  

Hippocampal CA1 apical neuropil atrophy in mild Alzheimer disease visualized with 7-T MRI
Kerchner et al.
Neurology 2010;75:1381-1387.
ABSTRACT | FULL TEXT  

Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia
Kadir and Nordberg
JNM 2010;51:1418-1430.
ABSTRACT | FULL TEXT  

Pittsburgh Compound B (11C-PIB) and Fluorodeoxyglucose (18 F-FDG) PET in Patients With Alzheimer Disease, Mild Cognitive Impairment, and Healthy Controls
Devanand et al.
J Geriatr Psychiatry Neurol 2010;23:185-198.
ABSTRACT  

Alzheimer Disease: Update on Basic Mechanisms
Bi
J Am Osteopath Assoc 2010;110:S3-S9.
ABSTRACT | FULL TEXT  

Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images
Tolboom et al.
J. Neurol. Neurosurg. Psychiatry 2010;81:882-884.
ABSTRACT | FULL TEXT  

Vascular and Degenerative Processes Differentially Affect Regional Interhemispheric Connections in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease
Lee et al.
Stroke 2010;41:1791-1797.
ABSTRACT | FULL TEXT  

Alzheimer disease identification using amyloid imaging and reserve variables: Proof of concept
Roe et al.
Neurology 2010;75:42-48.
ABSTRACT | FULL TEXT  

Blood-Borne Amyloid-{beta} Dimer Correlates with Clinical Markers of Alzheimer's Disease
Villemagne et al.
J. Neurosci. 2010;30:6315-6322.
ABSTRACT | FULL TEXT  

Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer's disease
Zhou et al.
Brain 2010;133:1352-1367.
ABSTRACT | FULL TEXT  

Ginkgo biloba and Cognitive Decline--Reply
Snitz et al.
JAMA 2010;303:1477-1478.
FULL TEXT  

Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
De Strooper
Physiol. Rev. 2010;90:465-494.
ABSTRACT | FULL TEXT  

Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB
Resnick et al.
Neurology 2010;74:807-815.
ABSTRACT | FULL TEXT  

Pittsburgh Compound B Imaging and Prediction of Progression From Cognitive Normality to Symptomatic Alzheimer Disease
Morris et al.
Arch Neurol 2009;66:1469-1475.
ABSTRACT | FULL TEXT  

Cognitive Decline and Brain Volume Loss as Signatures of Cerebral Amyloid-{beta} Peptide Deposition Identified With Pittsburgh Compound B: Cognitive Decline Associated With A{beta} Deposition
Storandt et al.
Arch Neurol 2009;66:1476-1481.
ABSTRACT | FULL TEXT  

High Striatal Amyloid {beta}-Peptide Deposition Across Different Autosomal Alzheimer Disease Mutation Types
Villemagne et al.
Arch Neurol 2009;66:1537-1544.
ABSTRACT | FULL TEXT  

Absence of Pittsburgh compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: a case report.
Cairns et al.
Arch Neurol 2009;66:1557-1562.
ABSTRACT | FULL TEXT  

Basal Cerebral Metabolism May Modulate the Cognitive Effects of A{beta} in Mild Cognitive Impairment: An Example of Brain Reserve
Cohen et al.
J. Neurosci. 2009;29:14770-14778.
ABSTRACT | FULL TEXT  

G Protein-Coupled Receptors, Cholinergic Dysfunction, and A{beta} Toxicity in Alzheimer's Disease
Thathiah and De Strooper
Sci Signal 2009;2:re8-re8.
ABSTRACT | FULL TEXT  

Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls
Scheinin et al.
Neurology 2009;73:1186-1192.
ABSTRACT | FULL TEXT  

Disruption of Functional Connectivity in Clinically Normal Older Adults Harboring Amyloid Burden
Hedden et al.
J. Neurosci. 2009;29:12686-12694.
ABSTRACT | FULL TEXT  

Amyloid imaging in the prediction of Alzheimer-type dementia in subjects with amnestic MCI
Visser and Knopman
Neurology 2009;73:744-745.
FULL TEXT  

Phase 1 Study of the Pittsburgh Compound B Derivative 18F-Flutemetamol in Healthy Volunteers and Patients with Probable Alzheimer Disease
Nelissen et al.
JNM 2009;50:1251-1259.
ABSTRACT | FULL TEXT  

Treatment with a C5aR Antagonist Decreases Pathology and Enhances Behavioral Performance in Murine Models of Alzheimer's Disease
Fonseca et al.
J. Immunol. 2009;183:1375-1383.
ABSTRACT | FULL TEXT  

Episodic memory loss is related to hippocampal-mediated {beta}-amyloid deposition in elderly subjects
Mormino et al.
Brain 2009;132:1310-1323.
ABSTRACT | FULL TEXT  

Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease
Jack et al.
Brain 2009;132:1355-1365.
ABSTRACT | FULL TEXT  

In vivo mapping of amyloid toxicity in Alzheimer disease
Frisoni et al.
Neurology 2009;72:1504-1511.
ABSTRACT | FULL TEXT  

Fibrillar amyloid-{beta} burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
Reiman et al.
Proc. Natl. Acad. Sci. USA 2009;106:6820-6825.
ABSTRACT | FULL TEXT  

Carbon 11-Labeled Pittsburgh Compound B and Carbon 11-Labeled (R)-PK11195 Positron Emission Tomographic Imaging in Alzheimer Disease
Wiley et al.
Arch Neurol 2009;66:60-67.
ABSTRACT | FULL TEXT