Amyloid imaging in dementias with atypical presentation

Abstract

We explored the potential value of amyloid imaging in patients with atypical presentations of dementia. Twenty-eight patients with atypical dementia underwent PET imaging with the amyloid imaging tracer Pittsburgh Compound-B (PiB). Twenty-six had [18F]fluoro-2-deoxy-D-glucose (FDG) PET scans. After extensive clinical evaluation, this group of patients generated considerable diagnostic uncertainty and received working diagnoses that included possible AD (pAD), focal dementias [e.g. posterior cortical atrophy (PCA)], or cases in which no clear diagnostic category could be determined (dementia of uncertain etiology; DUE). Patients were classified as PiB-positive, -negative, or -intermediate based on objective criteria. Anterior-posterior (A-P) and left-right (L-R) indices of PiB and FDG uptake were calculated to examine differences in distribution of amyloid pathology and metabolic changes associated with clinical phenotype. Eleven patients (39%) were PiB-positive, 16 were PiB-negative (57%) and one (4%) was intermediate. By diagnostic category, 3/10 patients (30%) with DUE, 1/5 (20%) with primary progressive aphasia (PPA), 3/5 (60%) with posterior cortical atrophy (PCA), and 4/7 (57%) with pAD were PiB-positive. Brain metabolism of both PiB-positive and -negative patients were generally similar by phenotype, but differed from typical AD. PCA patients also appeared to differ in their relative distribution of PiB compared to typical AD, consistent with their atypical phenotype. AD pathology is frequently present in atypical presentations of dementia and can be identified by amyloid imaging. Clinical phenotype is more related to the pattern of cerebral hypometabolism than the presence/absence of amyloid pathology. These findings have diagnostic, prognostic, and therapeutic implications.

Amyloid Imaging With 11C-PIB in Patients With Cognitive Impairment in a Clinical Setting

“…29,40 On the other hand, 3 of these 8 patients and the 7 patients with CD and DLB suspicion showed PIB retention, confirming that β-amyloid can be also present in other dementias not AD related. 41 Often, this kind of patients may have comorbidities or a mix of neurological pathologies in which the amyloid deposition can be unspecific, and 11 C-PIB may bind to neuritic plaques regardless the pathology. Of course, in this context, a negative 11 C-PIB has the greatest value.…”

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease

“…In previous studies of typical and atypical clinical presentations of Alzheimer's disease, there has been a dissociation between the rather diffuse distribution of amyloid-b plaques and the highly specific patterns of neurodegeneration that strongly correlate with symptomatology (Rabinovici et al, 2010;Wolk et al, 2012;Lehmann et al, 2013;Jung et al, 2015). It has often been suggested that tau pathology, rather than amyloid-b, may be driving disease manifestation (Desikan et al, 2012;Jack and Holtzman, 2013).…”

“…Among many other applications, amyloid-b imaging has been incorporated into diagnostic criteria for various stages of the disease (Albert et al, 2011;McKhann et al, 2011;Sperling et al, 2011;Dubois et al, 2014), has substantial impact on clinical decision-making (Ossenkoppele et al, 2013a;Sanchez-Juan et al, 2014) and patient management plans (Schipke et al, 2012;Grundman et al, 2013), and has shown potential as a surrogate outcome measure in clinical trials tailored to reduce cerebral amyloid-b plaque burden (Salloway et al, 2014;Liu et al, 2015). A yet unresolved issue after a decade of amyloid-b imaging research, however, is the disconnection between the diffuse distribution of amyloid-b pathology throughout the neocortex (Rabinovici et al, 2010;Wolk et al, 2012;Lehmann et al, 2013;Jung et al, 2015) and the selective patterns of brain atrophy and glucose hypometabolism that strongly correlate with clinical symptoms (Rabinovici et al, 2010;Ridgway et al, 2012;Lehmann et al, 2013;Madhavan et al, 2013). Thus, although amyloid-b deposition may be a prerequisite to developing Alzheimer's disease dementia, at some point during the disease course additional factors are likely involved in determining regional neurodegeneration and symptomatology.…”

Emerging Concepts in Alzheimer's Disease

“…Of interest, whereas structural (MRI) imaging has emphasized mesial temporal (e.g., hippocampal) atrophy (see above), FDG-PET scanning shows hypometabolism in the lateral temporoparietal and medial parietal cortex, including the precuneus and posterior cingulate gyrus (3,105). It is now possible to study a living brain using all of these modalities and to integrate or coregister the resultant data and correlate them with CSF markers (110)(111)(112)(113)(114). Much of this work has been accomplished through the Alzheimer Disease Neuroimaging Initiative (ADNI), a multicenter, multidisciplinary investigation charged with studying large numbers of subjects with early AD or MCI and comparing them with normal controls (110).…”