Imaging β-amyloid burden in aging and dementia

Rowe, Christopher C.; Ng, Serena; Ackermann, Uwe; Gong, Sylvia; Pike, Kerryn E.; Savage, Greg; Cowie, Tiffany; Dickinson, Kerryn L; Maruff, Paul; Darby, David; Smith, Charmaine; Woodward, Mark; Merory, John; Tochon-Danguy, Henri; O’Keefe, Graeme; Klunk, William E.; Mathis, C. A.; Price, Julie C.; Masters, Colin L.; Villemagne, Victor L.

doi:10.1212/01.wnl.0000261919.22630.ea

Cited by 990 publications

(894 citation statements)

References 55 publications

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“…PIB also demonstrated the ability to discriminate between healthy young controls and older patients, with no significant retention seen in controls [6]. Subsequent studies were able to demonstrate congruence of findings, with retention of PIB and diagnosis consistent with AD [7][8][9][10] . Equivocal findings in patients with PIB retention and clinical diagnoses of MCI are variable likely owing to cofounders, including amnesia, depression, and alternative dementias playing a role.…”

Section: Compounds Of Interestmentioning

confidence: 84%

Amyloid Imaging: Poised for Integration into Medical Practice

Anand

Sabbagh

2017

Neurotherapeutics

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Amyloid imaging represents a significant advance as an adjunct in the diagnosis of Alzheimer's disease (AD) because it is the first imaging modality that identifies in vivo changes known to be associated with the pathogenesis. Initially, 11 C-PIB was developed, which was the prototype for many 18 F compounds, including florbetapir, florbetaben, and flutemetamol, among others. Despite the high sensitivity and specificity of amyloid imaging, it is not commonly used in clinical practice, mainly because it is not reimbursed under current Center for Medicare and Medicaid Services guidelines in the USA. To guide the field in who would be most appropriate for the utility of amyloid positron emission tomography, current studies are underway [Imaging Dementia Evidence for Amyloid Scanning (IDEAS) Study] that will inform the field on the utilization of amyloid positron emission tomography in clinical practice. With the advent of monoclonal antibodies that specifically target amyloid antibody, there is an interest, possibly a mandate, to screen potential treatment recipients to ensure that they are suitable for treatment. In this review, we summarize progress in the field to date.

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Section: Compounds Of Interestmentioning

confidence: 84%

Amyloid Imaging: Poised for Integration into Medical Practice

Anand

Sabbagh

2017

Neurotherapeutics

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“…This increased retention is reported to be lower than that observed in AD subjects. The different increase in 11 C-PIB PET retention reported in normal controls, AD and DLB patients reflects a broad range of Aβ deposition [31] which may be related to the degree of microglia activation and/or CX3CR1 expression [30].…”

Section: Amyloid Imagingmentioning

confidence: 92%

“…Preliminary studies report that cognitively normal elderly subjects show an increased 11 C-PIB retention in the prefrontal and posterior cingulate/precuneus regions [31]. This increased retention is reported to be lower than that observed in AD subjects.…”

Section: Amyloid Imagingmentioning

confidence: 93%

“…Pittsburgh compound B [PIB; 2-(4′-methylaminophenyl)-6-hydroxybenzothiazole or 6-OH-BTA-1] binds specifically to fibrils of Aβ40 peptides and is a sensitive marker for Aβ pathology in mild cognitive impairment (MCI) and AD. PIB has provided quantitative information on Aβ burden, leading to new insights into Aβ deposition in neurodegenerative disease in which Aβ may play a role [31]. PET studies have shown not only a significative difference in 11 C-PIB retention between agematched healthy controls and AD patients [31], but also inverse correlations with glucose hypometabolism [31].…”

Section: Amyloid Imagingmentioning

confidence: 99%

“…PIB has provided quantitative information on Aβ burden, leading to new insights into Aβ deposition in neurodegenerative disease in which Aβ may play a role [31]. PET studies have shown not only a significative difference in 11 C-PIB retention between agematched healthy controls and AD patients [31], but also inverse correlations with glucose hypometabolism [31]. Furthermore, comparison of the diagnostic utility of Aβ versus 2-[ 18 F]-fluoro-2-deoxy-D-glucose ( 18 F-FDG) imaging demonstrated that PIB imaging may provide an additional tool for the diagnosis of AD [32].…”

Section: Amyloid Imagingmentioning

confidence: 99%

See 2 more Smart Citations

Imaging of neuroinflammation

Ciarmiello

2011

Eur J Nucl Med Mol Imaging

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The Aging Brain and Cognition

Marchant¹,

Reed²,

Sanossian³

et al. 2013

JAMA Neurol

117

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Importance: ␤-Amyloid (A␤) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD).Objective: To examine the relationship between neuroimaging measures of VBI and brain A␤ deposition and their associations with cognition. Design and Setting:A cross-sectional study in a community-and clinic-based sample recruited for elevated vascular disease risk factors. Participants: Clinically normal (mean age, 77.1 years [N = 30]), cognitively impaired (mean age, 78.0 years [N = 24]), and mildly demented (mean age, 79.8 years [N=7]) participants. Interventions: Magnetic resonance imaging, A␤ (Pittsburgh Compound B-positron emission tomographic [PiB-PET]) imaging, and cognitive testing.Main Outcome Measures: Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early A␤ deposition; PiB positivity (29 PiBpositive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory.Results: Vascular brain injury and A␤ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P Ͻ .05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI. Conclusions and Relevance:In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than A␤ in contemporaneous cognitive function and remained predictive after including the possible influence of A␤. There was no evidence that VBI increases the likelihood of A␤ deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment.

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Imaging β-amyloid burden in aging and dementia

Cited by 990 publications

References 55 publications

Amyloid Imaging: Poised for Integration into Medical Practice

Amyloid Imaging: Poised for Integration into Medical Practice

Imaging of neuroinflammation

The Aging Brain and Cognition

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