%0 Journal Article %J J Alzheimers Dis %D 2019 %T Why Is Amyloid-β PET Requested After Performing Cerebrospinal Fluid Biomarkers? %A Reimand, Juhan %A Groot, Colin %A Teunissen, Charlotte E %A Windhorst, Albert D %A Boellaard, Ronald %A Barkhof, Frederik %A Nazarenko, Sergei %A van der Flier, Wiesje M %A van Berckel, Bart N M %A Scheltens, Philip %A Ossenkoppele, Rik %A Bouwman, Femke %X

BACKGROUND: Amyloid-β PET and cerebrospinal fluid (CSF) Aβ42 are considered interchangeable for clinical diagnosis of Alzheimer's disease.

OBJECTIVE: To explore the clinical reasoning for requesting additional amyloid-β PET after performing CSF biomarkers.

METHODS: We retrospectively identified 72 memory clinic patients who underwent amyloid-β PET after CSF biomarkers analysis for clinical diagnostic evaluation between 2011 and 2019. We performed patient chart reviews to identify factors which led to additional amyloid-β PET. Additionally, we assessed accordance with appropriate-use-criteria (AUC) for amyloid-β PET.

RESULTS: Mean patient age was 62.0 (SD = 8.1) and mean Mini-Mental State Exam score was 23.6 (SD = 3.8). CSF analysis conflicting with the clinical diagnosis was the most frequent reason for requesting an amyloid-β PET scan (n = 53, 74%), followed by incongruent MRI (n = 16, 22%), unusual clinical presentation (n = 11, 15%) and young age (n = 8, 11%). An amyloid-β PET scan was rarely (n = 5, 7%) requested in patients with a CSF Aβ+/tau+ status. Fifteen (47%) patients with a post-PET diagnosis of AD had a predominantly non-amnestic presentation. In n = 11 (15%) cases, the reason that the clinician requested amyloid-β was not covered by AUC. This happened most often (n = 7) when previous CSF analysis did not support current clinical diagnosis, which led to requesting amyloid-β PET.

CONCLUSION: In this single-center study, the main reason for requesting an amyloid-β PET scan after performing CSF biomarkers was the occurrence of a mismatch between the primary clinical diagnosis and CSF Aβ/tau results.

%B J Alzheimers Dis %V 73 %P 559-569 %8 2020 Jan 21 %G eng %N 2 %R 10.3233/JAD-190836 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Quantitative PET and Histology of Brain Biopsy Reveal Lack of Selective Pittsburgh Compound-B Binding to Intracerebral Amyloidoma. %A Groot, Colin %A Tolboom, Nelleke %A Ikonomovic, Milos D %A Lammertsma, Adriaan A %A Boon, Baayla D C %A Barkhof, Frederik %A Scheltens, Philip %A Klunk, William E %A Rozemuller, Annemieke J M %A Ossenkoppele, Rik %A van Berckel, Bart N M %X

This single case study examines selective Pittsburgh compound-B (PiB) binding to an intracerebral light-chain amyloidoma using a 90-minute dynamic [11C]PiB-PET scan and brain biopsy tissue. Parametric non-displaceable binding potential (BPND) images showed low specific binding in the amyloidoma (BPND = 0.23), while relative tracer delivery was adequate (R1 = 0.44). Histology of the tissue revealed strong coloring with Congo-red, thioflavin-S, and X-34, indicating presence of amyloid. However, immunological staining with 6F/3D revealed absence of amyloid-β and histofluorescence of 6-CN-PiB, a highly fluorescent derivative of PiB, was at background levels. Our results suggest that PiB does not detect the atypical amyloid pathology associated with an intracerebral light-chain amyloidoma. These findings are of interest to clinicians and researchers applying [11C]PiB-PET to detect atypical forms of amyloid pathology.

%B J Alzheimers Dis %8 2018 Jul 18 %G eng %R 10.3233/JAD-180316 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Diagnostic Accuracy of MRI and Additional [18F]FDG-PET for Behavioral Variant Frontotemporal Dementia in Patients with Late Onset Behavioral Changes. %A Vijverberg, Everard G B %A Wattjes, Mike P %A Dols, Annemiek %A Krudop, Welmoed A %A Möller, Christiane %A Peters, Anne %A Kerssens, Cora J %A Gossink, Flora %A Prins, Niels D %A Stek, Max L %A Scheltens, Philip %A van Berckel, Bart N M %A Barkhof, Frederik %A Pijnenburg, Yolande A L %X

BACKGROUND: Neuroimaging has a reasonable accuracy to differentiate behavioral variant frontotemporal dementia (bvFTD) from other neurodegenerative disorders, its value for the differentiation of bvFTD among subjects with acquired behavioral disturbances is unknown.

OBJECTIVE: To determine the diagnostic accuracy of MRI, additional [18F]FDG-PET, and their combination for bvFTD among subjects with late onset behavioral changes.

METHODS: Patients with late onset behavioral changes referred to a memory clinic or psychiatric services were included. At baseline, 111 patients had a brain MRI scan and 74 patients received an additional [18F]FDG-PET when the MRI was inconclusive. The consensus diagnosis after two-year-follow-up was used as the gold standard to calculate sensitivity and specificity for baseline neuroimaging.

RESULTS: 27 patients had probable/definite bvFTD and 84 patients had a non-bvFTD diagnosis (primary psychiatric diagnosis or other neurological disorders). MRI had a sensitivity of 70% (95% CI 52-85%) with a specificity of 93% (95% CI 86-97%). Additional [18F]FDG-PET had a sensitivity of 90% (95% CI 66-100%) with a specificity of 68% (95% CI 56-79%). The sensitivity of combined neuroimaging was 96% (95% CI 85-100%) with a specificity of 73% (95% CI 63-81%). In 66% of the genetic FTD cases, MRI lacked typical frontotemporal atrophy. 40% of cases with a false positive [18F]FDG-PET scan had a primary psychiatric diagnosis.

CONCLUSION: A good diagnostic accuracy was found for MRI and additional [18F]FDG-PET for bvFTD in patients with late onset behavioral changes. Caution with the interpretation of neuroimaging results should especially be taken in cases with a genetic background and in cases with a primary psychiatric differential diagnosis where [18F]FDG-PET is the only abnormal investigation.

%B J Alzheimers Dis %V 53 %P 1287-97 %8 2016 Jun 30 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27372646?dopt=Abstract %R 10.3233/JAD-160285 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Heterogeneous Language Profiles in Patients with Primary Progressive Aphasia due to Alzheimer's Disease. %A Louwersheimer, Eva %A Keulen, M Antoinette %A Steenwijk, Martijn D %A Wattjes, Mike P %A Jiskoot, Lize C %A Vrenken, Hugo %A Teunissen, Charlotte E %A van Berckel, Bart N M %A van der Flier, Wiesje M %A Scheltens, Philip %A van Swieten, John C %A Pijnenburg, Yolande A L %K Aged %K Alzheimer Disease %K Aphasia, Primary Progressive %K Atrophy %K Biomarkers %K Brain %K Female %K Humans %K Language %K Language Tests %K Magnetic Resonance Imaging %K Male %K Mental Status Schedule %K Organ Size %K Positron-Emission Tomography %K Retrospective Studies %X

BACKGROUND: The logopenic variant of Primary Progressive Aphasia (lvPPA) is associated with underlying Alzheimer's disease (AD) pathology and characterized by impaired single word retrieval and repetition of phrases and sentences.

OBJECTIVE: We set out to study whether logopenic aphasia is indeed the prototypic language profile in PPA patients with biomarker evidence of underlying AD pathology and to correlate language profiles with cortical atrophy patterns on MRI.

METHODS: Inclusion criteria: (I) clinical diagnosis of PPA; (II) CSF profile and/or PiB-PET scan indicative for amyloid pathology; (III) availability of expert language evaluation. Based on language evaluation, patients were classified as lvPPA (fulfilling lvPPA core criteria), lvPPA extended (fulfilling core criteria plus other language disturbances), or PPA unclassifiable (not fulfilling lvPPA core criteria). Cortical atrophy patterns on MRI were visually rated and quantitative measurements of cortical thickness were performed using FreeSurfer.

RESULTS: We included 22 patients (age 67±7 years, 50% female, MMSE 21±6). 41% were classified as lvPPA, 36% as lvPPA extended with additional deficits in language comprehension and/or confrontation naming, and 23% as PPA unclassifiable. By both qualitative and quantitative measurements, patients with lvPPA showed mild global cortical atrophy on MRI, whereas patients with lvPPA extended showed more focal cortical atrophy, predominantly at the left tempo-parietal side. For PPA unclassifiable, qualitative measurements revealed a heterogeneous atrophy pattern.

CONCLUSION: Although most patients fulfilled the lvPPA criteria, we found that their language profiles were heterogeneous. The clinical and radiological spectrum of PPA due to underlying AD pathology is broader than pure lvPPA.

%B J Alzheimers Dis %V 51 %P 581-90 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26890751?dopt=Abstract %R 10.3233/JAD-150812