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

Memory and Aging Center, Department of Neurology, University of California San Francisco, 350 Parnassus Avenue, Suite 905, San Francisco, CA 94143, USA. .
Alzheimer's Research and Therapy (Impact Factor: 3.98). 11/2011; 3(6):31. DOI: 10.1186/alzrt93
Source: PubMed
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.

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    • "In fact, ratings were tpvCBS on all methods of assessment suggesting underlying AD pathology . Importantly, significant neuritic plaques (and positive amyloid PET) can also be seen in 15% to 30% of cognitively normal older individuals [37]. Therefore, while a negative amyloid scan 'rules out' AD with high likelihood in patients presenting with CBS, a positive scan does not exclude a co-pathology that may be the primary etiology of symptoms, particularly in patients with frontal features which are most strongly associated with underlying FTLD pathology. "
    [Show abstract] [Hide abstract] ABSTRACT: Group comparisons demonstrate greater visuospatial and memory deficits and temporoparietal-predominant degeneration on neuroimaging in patients with corticobasal syndrome (CBS) found to have Alzheimer's disease (AD) pathology versus those with underlying frontotemporal lobar degeneration (FTLD). The value of these features in predicting underlying AD pathology in individual patients is unknown. The goal of this study is to evaluate the utility of modified clinical criteria and visual interpretations of magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting amyloid deposition (as a surrogate of Alzheimer's disease neuropathology) in patients presenting with CBS. In total, 25 patients meeting CBS core criteria underwent amyloid (Pittsburgh compound B; PIB) PET scans. Clinical records, MRI, and FDG scans were reviewed blinded to PIB results. Modified clinical criteria were used to classify CBS patients as temporoparietal variant CBS (tpvCBS) or frontal variant CBS (fvCBS). MRI and FDG-PET were classified based on the predominant atrophy/hypometabolism pattern (frontal or temporoparietal). A total of 9 out of 13 patients classified as tpvCBS were PIB+, compared to 2out of 12 patients classified as fvCBS (P < 0.01, sensitivity 82%, specificity 71% for PIB+ status). Visual MRI reads had 73% sensitivity and 46% specificity for PIB+ status with moderate intra-rater reliability (Cohen's kappa = 0.42). Visual FDG reads had higher sensitivity (91%) for PIB+ status with perfect intra-rater reliability (kappa = 1.00), though specificity was low (50%). PIB results were confirmed in all 8 patients with available histopathology (3 PIB+ with confirmed AD, 5 PIB- with FTLD). Splitting CBS patients into frontal or temporoparietal clinical variants can help predict the likelihood of underlying AD, but criteria require further refinement. Temporoparietal-predominant neuroimaging patterns are sensitive but not specific for AD.
    Full-text · Article · Dec 2015 · Alzheimer's Research and Therapy
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    • "Among the factors to be considered are its lack of correlation with cognitive status and neuronal injury biomarkers and its low performance in predicting progression or differentiating between subtypes of MCI [68]. Amyloid PET is only a marker of amyloid pathology in vivo and lacks diagnostic power in differentiating between different AD variants, DLB and cerebral amyloid angiopathy [69, 70]. Nonetheless, there are several clinical situations in which amyloid PET has a crucial role, for example in early-onset atypical presentations and in the primary progressive aphasia spectrum (e.g. "
    [Show abstract] [Hide abstract] ABSTRACT: The process leading to the identification and validation of biomarkers for the diagnosis of early Alzheimer’s disease (early AD) has been a major focus of research interest in the past 10 years, and has been accompanied by a debate on the feasibility of implementing the research criteria in clinical practice. In the context of imaging performed using the two currently identified classes of AD biomarkers, i.e. markers of pathology and neurodegeneration, amyloid PET and 18F-FDG PET imaging are decisive tools whose crucial value is acknowledged in the recent guidelines for the early diagnosis of AD and other dementia conditions. The available recommendations draw on an extensive body of PET imaging literature, based mainly on visual methods. For the research criteria to be adopted in clinical settings, several uncertainties and gaps in knowledge must be overcome, in particular the low sensitivity and specificity provided by visual qualitative PET scan evaluation at the single-subject level. Indeed, the sensitivity and specificity of the 18F-FDG PET methods depend largely on the use of “objective methods” that result in improved accuracy for diagnosis and prognosis. Here, we review the most widely used parametric and semi-quantitative approaches to 18F-FDG PET and amyloid PET imaging, highlighting their importance in early and differential diagnosis in both research and clinical settings.
    Preview · Article · Aug 2014
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    • "Moreover, such biomarkers may also make it possible to achieve early etiological characterization of the prodromal stage of dementia, also known as mild cognitive impairment (MCI) [9]. This is a particularly important aspect, given that the disease-modifying drugs currently under development are expected to be more effective in the early disease phase [10]. Neuronal damage or dysfunction and specific pathological features of dementias are the targets of the most widely validated PET biomarkers [11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo imaging techniques that, using a wide range of tracers, allow the non-invasive tracking of pathophysiological processes in healthy and diseased brain. One of most promising of the various PET and SPECT applications is the investigation of pathophysiological aspects of neurodegenerative disorders. This is an extremely important area of investigation given the aging of the global population and the high prevalence of brain disorders such as Alzheimer’s disease and Parkinson’s disease in elderly persons. Clinical translation of advances in molecular imaging research into clinical practice may, by overcoming the limitations of a diagnostic approach that relies exclusively on clinical judgment and structural imaging, lead to better clinical management of affected patients.
    Preview · Article · Dec 2013
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