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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

Diagnostic impact of [18F]flutemetamol PET in early-onset dementia

Authors: Marissa D. Zwan, Femke H. Bouwman, Elles Konijnenberg, Wiesje M. van der Flier, Adriaan A. Lammertsma, Frans R. J. Verhey, Pauline Aalten, Bart N. M. van Berckel, Philip Scheltens

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

Early-onset dementia patients often present with atypical clinical symptoms, hampering an accurate clinical diagnosis. The purpose of the present study was to assess the diagnostic impact of the amyloid-positron emission tomography (PET) imaging agent [18F]flutemetamol in early-onset dementia patients, in terms of change in (confidence in) diagnosis and patient management plan.

Methods

This prospective bi-center study included 211 patients suspected of early-onset dementia who visited a tertiary memory clinic. Patients were eligible with Mini Mental State Examination ≥ 18 and age at diagnosis ≤ 70 years and in whom the diagnostic confidence was <90% after routine diagnostic work-up. All patients underwent [18F]flutemetamol PET, which was interpreted as amyloid-negative or amyloid-positive based on visual rating. Before and after disclosing the PET results, we assessed the diagnostic confidence (using a visual analog scale of 0–100%) and clinical diagnosis. The impact of [18F]flutemetamol PET on the patient management plan was also evaluated.

Results

[18F]flutemetamol PET scans were positive in 133 out of 211 (63%) patients, of whom 110 out of 144 (76%) patients had a pre-PET Alzheimer’s disease (AD) diagnosis and 23 out of 67 (34%) patients had a non-AD diagnosis. After disclosure of PET results, 41/211 (19%) diagnoses changed. Overall, diagnostic confidence increased from 69 ± 12% to 88 ± 15% after disclosing PET results (P < 0.001; in 87% of patients). In 79 (37%) patients, PET results led to a change in patient management and predominantly the initiation of AD medication when PET showed evidence for amyloid pathology.

Conclusions

[18F]flutemetamol PET changed clinical diagnosis, increased overall diagnostic confidence, and altered the patient management plan. Our results suggest that amyloid PET may have added value over the standardized diagnostic work-up in early-onset dementia patients with uncertain clinical diagnosis. This study provides evidence for the recommendations put forward in the appropriate use criteria for amyloid PET in clinical practice.

Trial registration

Nederlands Trial Register NTR3743. Registered 7 December 2012.
Literature
1.
Koedam EL, Lauffer V, van der Vlies AE, van der Flier WM, Scheltens P, Pijnenburg YA. Early-versus late-onset Alzheimer’s disease: more than age alone. J Alzheimers Dis. 2010;19:1401–8.PubMed
2.
Smits LL, Pijnenburg YA, Koedam EL, van der Vlies AE, Reuling IE, Koene T, et al. Early onset Alzheimer’s disease is associated with a distinct neuropsychological profile. J Alzheimers Dis. 2012;30:101–8.PubMed
3.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefPubMedPubMedCentral
4.
Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9:e-16.CrossRef
5.
Schipke CG, Peters O, Heuser I, Grimmer T, Sabbagh MN, Sabri O, et al. Impact of beta-amyloid-specific florbetaben PET imaging on confidence in early diagnosis of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2012;33:416–22.CrossRefPubMed
6.
Ossenkoppele R, Prins ND, Pijnenburg YA, Lemstra AW, van der Flier WM, Adriaanse SF, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement. 2013;9:414–21.CrossRefPubMed
7.
Grundman M, Pontecorvo MJ, Salloway SP, Doraiswamy PM, Fleisher AS, Sadowsky CH, et al. Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline. Alzheimer Dis Assoc Disord. 2013;27:4–15.CrossRefPubMed
8.
Frederiksen KS, Hasselbalch SG, Hejl AM, Law I, Hojgaard L, Waldemar G. Added diagnostic value of (11)C-PiB-PET in memory clinic patients with uncertain diagnosis. Dement Geriatr Cogn Dis Extra. 2012;2:610–21.CrossRefPubMedPubMedCentral
9.
Sanchez-Juan P, Ghosh PM, Hagen J, Gesierich B, Henry M, Grinberg LT, et al. Practical utility of amyloid and FDG-PET in an academic dementia center. Neurology. 2014;82:230–8.CrossRefPubMedPubMedCentral
10.
Zannas AS, Doraiswamy PM, Shpanskaya KS, Murphy KR, Petrella JR, Burke JR, et al. Impact of (1)(8)F-florbetapir PET imaging of beta-amyloid neuritic plaque density on clinical decision-making. Neurocase. 2014;20:466–73.CrossRefPubMed
11.
Mitsis EM, Bender HA, Kostakoglu L, Machac J, Martin J, Woehr JL, et al. A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition. Mol Neurodegener. 2014;9:10.CrossRefPubMedPubMedCentral
12.
van der Flier WM, Pijnenburg YA, Prins N, Lemstra AW, Bouwman FH, Teunissen CE, et al. Optimizing patient care and research: the Amsterdam Dementia Cohort. J Alzheimers Dis. 2014;41:313–27.PubMed
13.
Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.CrossRefPubMedPubMedCentral
14.
Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43:250–60.CrossRefPubMed
15.
McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863–72.CrossRefPubMed
16.
Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol. 2003;54:S15–9.CrossRefPubMed
17.
Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996;47:1–9.CrossRefPubMed
18.
Surti S, Kuhn A, Werner ME, Perkins AE, Kolthammer J, Karp JS. Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities. J Nucl Med. 2007;48:471–80.PubMed
19.
Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, et al. Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc. 1999;47:564–9.CrossRefPubMed
20.
Mok W, Chow TW, Zheng L, Mack WJ, Miller C. Clinicopathological concordance of dementia diagnoses by community versus tertiary care clinicians. Am J Alzheimers Dis Other Demen. 2004;19:161–5.CrossRefPubMedPubMedCentral
21.
Beach TG, Monsell SE, Philips LE, Kukall W. Accuracy of the clinical diagnosis of alzheimer disease at National Institute on Aging Alzheimer’s Disease Centers, 2005–2010. J Neuropathol Exp Neurol. 2012;71:266–73.CrossRefPubMedPubMedCentral
22.
Dugger BN, Adler CH, Shill HA, Caviness J, Jacobson S, Driver-Dunckley E, et al. Concomitant pathologies among a spectrum of parkinsonian disorders. Parkinsonism Relat Disord. 2014;20:525–9.CrossRefPubMedPubMedCentral
23.
Zwan MD, Okamura N, Fodero-Tavoletti MT, Furumoto S, Masters CL, Rowe CC, et al. Voyage au bout de la nuit: Abeta and tau imaging in dementias. Q J Nucl Med Mol Imaging. 2014;58:398–412.PubMed
24.
Chételat G, Ossenkoppele R, Villemagne VL, Perrotin A, Landeau B, Mézenge F, et al. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer’s disease. Brain. 2016;139:2528–39.CrossRefPubMed
25.
Rinne JO, Wong DF, Wolk DA, Leinonen V, Arnold SE, Buckley C, et al. [(18)F]Flutemetamol PET imaging and cortical biopsy histopathology for fibrillar amyloid beta detection in living subjects with normal pressure hydrocephalus: pooled analysis of four studies. Acta Neuropathol. 2012;124:833–45.CrossRefPubMed
26.
Leinonen V, Rinne JO, Wong DF, Wolk DA, Trojanowski JQ, Sherwin PF, et al. Diagnostic effectiveness of quantitative [(1)(8)F]flutemetamol PET imaging for detection of fibrillar amyloid beta using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus. Acta Neuropathol Commun. 2014;2:46.CrossRefPubMedPubMedCentral
27.
Wong DF, Moghekar AR, Rigamonti D, Brasic JR, Rousset O, Willis W, et al. An in vivo evaluation of cerebral cortical amyloid with [18 F]flutemetamol using positron emission tomography compared with parietal biopsy samples in living normal pressure hydrocephalus patients. Mol Imaging Biol. 2013;15:230–7.CrossRefPubMedPubMedCentral
28.
Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313:1939–49.CrossRefPubMedPubMedCentral
29.
Bensaidane MR, Beauregard JM, Poulin S, Buteau FA, Guimond J, Bergeron D, et al. Clinical utility of amyloid PET imaging in the differential diagnosis of atypical dementias and its impact on caregivers. J Alzheimers Dis. 2016;52:1251–62.CrossRefPubMed
Metadata
Title
Diagnostic impact of [18F]flutemetamol PET in early-onset dementia
Authors
Marissa D. Zwan
Femke H. Bouwman
Elles Konijnenberg
Wiesje M. van der Flier
Adriaan A. Lammertsma
Frans R. J. Verhey
Pauline Aalten
Bart N. M. van Berckel
Philip Scheltens
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-016-0228-4

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