Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications.

Robert Laforce,Gil D Rabinovici

doi:10.1186/alzrt93

Abstract

In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique.

Highlights

Positron emission tomography (PET) with amyloid ligands has revolutionized neuroimaging of aging and dementiaPittsburgh Compound B (PIB)-PET has rapidly become an integral part of research studies on cognitive aging and the evolution of Alzheimer’s disease (AD)
In 62 AD patients and 45 frontotemporal lobar degeneration (FTLD) patients matched for age and disease severity, PIB visual reads had a higher sensitivity for AD than FDG-PET (89.5% vs. 77.5%), with similar specificity (83% vs. 84%)
The recommendations were formulated using the following principles: amyloid PET cannot be interpreted in the absence of clinical context; amyloid PET will be most useful in differentiating amyloid beta (Aβ) from non-Aβ causes of dementia in scenarios in which this distinction is clinically challenging – these scenarios might include patients with mild symptoms, cases presenting with pathologically heterogeneous clinical syndromes, patients with early age-of-onset dementia, or cases with symptoms that could be explained by either Aβ processes or nondegenerative causes; and, some very important applications of amyloid PET should be restricted to research studies

Summary

Introduction

Positron emission tomography (PET) with amyloid ligands has revolutionized neuroimaging of aging and dementia. On autopsy the patient was found to have both Pick’s disease and high-likelihood AD (CERAD frequent/ Braak 5) This case demonstrates that while PIB can accurately detect AD pathology, a positive amyloid scan does not rule out comorbid non-Aβ pathology, which in this case was FTLD, as predicted based on the clinical presentation and FDG-PET pattern. The recommendations were formulated using the following principles: amyloid PET cannot be interpreted in the absence of clinical context (as is the case with any diagnostic test); amyloid PET will be most useful in differentiating Aβ from non-Aβ causes of dementia in scenarios in which this distinction is clinically challenging – these scenarios might include patients with mild symptoms (for example, MCI), cases presenting with pathologically heterogeneous clinical syndromes (for example, PPA, CBS), patients with early age-of-onset dementia, or cases with symptoms that could be explained by either Aβ processes or nondegenerative causes (for example, NPH, intracranial microhemorrhages); and, some very important applications of amyloid PET should be restricted to research studies (for example, scanning asymptomatic or minimally symptomatic patients)

Conclusions

Findings

Jagust WJ