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Journals
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issn:0003-99.2
1.  In Vivo Fibrillar β-Amyloid Detected Using [11C]PiB Positron Emission Tomography and Neuropathologic Assessment in Older Adults 
Archives of neurology  2011;68(2):232-240.
Background
In demented older adults, in vivo amyloid imaging shows agreement with diagnostic neuropathologic assessment of β-amyloid (Aβ). However, the extent of agreement in nondemented older adults remains unclear.
Objective
To compare Aβ quantified using in vivo carbon 11–labeled Pittsburgh Compound B positron emission tomography and postmortem neuropathologic assessment of Aβ in older adults.
Design
Case series.
Setting
Community-dwelling older adults who came to autopsy.
Participants
Five nondemented and 1 demented participant from the Baltimore Longitudinal Study of Aging.
Main Outcome Measure
Agreement between the mean cortical distribution volume ratio and the Consortium to Establish a Registry for AD (CERAD) neuritic plaque (NP) score used for pathologic diagnosis of Alzheimer disease.
Results
Of the 6 participants, 4 had moderate NPs, 2 had sparse or no detectable NPs, and 3 had microscopic findings of cerebral amyloid angiopathy at autopsy. On in vivo imaging, the mean cortical distribution volume ratio ranged from 0.96 to 1.59. Although there was agreement between in vivo amyloid imaging and CERAD NP scores in participants with either high or negligible Aβ levels in vivo, only limited agreement was observed among those with intermediate levels of Aβ. The best overall agreement was achieved at a distribution volume ratio of 1.2.
Conclusions
In older adults, variable agreement between in vivo imaging and CERAD NP score was observed. The limited agreement may, in part, reflect differences in typical measurements of Aβ using imaging compared with the CERAD neuropathologic protocol. Direct quantification of regional Aβ in relation to in vivo imaging is necessary to further enhance our understanding of the imaging–pathologic assessment correlation.
doi:10.1001/archneurol.2010.357
PMCID: PMC3082956  PMID: 21320990
2.  Absence of PIttsburgh Compound B Detection of CerebralAmyloid Beta in a Patient With Clinical, Cognitive, and Cerebrospinal FluidMarkers of Alzheimer Disease 
Archives of neurology  2009;66(12):1557-1562.
Objective
To determine the temporal relationships of clinical, cognitive, Pittsburgh Compound-B (PiB) amyloid imaging, and cerebrospinal fluid (CSF) markers of Alzheimer’s disease (AD).
Design
A case report of a longitudinally assessed participant in a memory and aging study who had serial clinical and psychometric assessments over 6 years, in addition to PiB imaging and CSF biomarker assays, prior to coming to autopsy.
Setting
Alzheimer’s Disease Research Center
Findings
An 85-year old individual was cognitively normal at his initial and next 3 annual assessments. Decline in measures of episodic memory and, to a lesser degree, working memory began at about age 88 years. PiB-PET amyloid imaging was negative at age 88.5 years, but at age 89.5 years there was reduced amyloid-beta 42 (Aβ42) and elevated levels of tau in the CSF. At his 6th assessment, when he was 90 years old, he was diagnosed with very mild dementia of the Alzheimer type. After death at age 91 years, the autopsy revealed foci of frequent neocortical diffuse Aβ plaques, sufficient to fulfill Khachaturian neuropathologic criteria for AD, but neuritic plaques and neurofibrillary tangles were sparse. Postmortem biochemical analysis of the cerebral tissue confirmed that PiB-PET-binding was below the level needed for in vivo detection.
Conclusion
Clinical, cognitive, and CSF markers consistent with AD may precede detection of cerebral Aβ with amyloid imaging agents such as PiB, which primarily label fibrillar Aβ plaques.
doi:10.1001/archneurol.2009.279
PMCID: PMC2796200  PMID: 20008664
3.  Carbon 11–Labeled Pittsburgh Compound B and Carbon 11–Labeled (R)-PK11195 Positron Emission Tomographic Imaging in Alzheimer Disease 
Archives of neurology  2009;66(1):60-67.
Background
Alzheimer disease (AD) is defined neuropathologically by the presence of neurofibrillary tangles and plaques associated with tau and β-amyloid protein deposition. The colocalization of microglia and β-amyloid plaques has been widely reported in pathological examination of AD and suggests that neuroinflammation may play a role in pathogenesis and/or progression. Because postmortem histopathological analyses are limited to single end-stage assessment, the time course and nature of this relationship are not well understood.
Objective
To image microglial activation and β-amyloid deposition in the brains of subjects with and without AD.
Design, Setting, and Participants
Using two carbon 11 ([11C])–labeled positron emission tomographic imaging agents, Pittsburgh Compound B (PiB) and (R)-PK11195, we examined the relationship between amyloid deposition and microglial activation in different stages of AD using 5 control subjects, 6 subjects diagnosed with mild cognitive impairment, and 6 patients with mild to moderate AD.
Results
Consistent with prior reports, subjects with a clinical diagnosis of probable AD showed significantly greater levels of [11C]PiB retention than control subjects, whereas patients with mild cognitive impairment spanned a range from control-like to AD-like levels of [11C]PiB retention. Additionally, 2 asymptomatic control subjects also exhibited evidence of elevated PiB retention in regions associated with the early emergence of plaques in AD and may represent prodromal cases of AD. We observed no differences in brain [11C](R)-PK11195 retention when subjects were grouped by clinical diagnosis or the presence or absence of β-amyloid pathological findings as indicated by analyses of [11C]PiB retention.
Conclusions
These findings suggest that either microglial activation is limited to later stages of severe AD or [11C](R)-PK11195 is too insensitive to detect the level of microglial activation associated with mild to moderate AD.
doi:10.1001/archneurol.2008.511
PMCID: PMC2666881  PMID: 19139300
4.  Biopsy Support for the Validity of Pittsburgh Compound B Positron Emission Tomography With a Twist 
Archives of neurology  2008;65(10):1281-1283.
doi:10.1001/archneur.65.10.1281
PMCID: PMC2637565  PMID: 18852340
5.  Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly 
Archives of neurology  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.
doi:10.1001/archneur.65.11.1509
PMCID: PMC2636844  PMID: 19001171

Results 1-5 (5)