[18F]FDG PET may differentiate cerebral amyloid angiopathy from Alzheimer’s disease
Sébastien Bergeret
Department of Nuclear Medicine, CHU French West Indies, Fort-de-France, France
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (equal)
Search for more papers by this authorMathieu Queneau
Department of Nuclear Medicine, Centre Cardiologique du Nord, Saint-Denis, France
Contribution: Data curation (equal), Writing - review & editing (supporting)
Search for more papers by this authorMathieu Rodallec
Department of Radiology, Centre Cardiologique du Nord, Saint-Denis, France
Contribution: Data curation (equal), Writing - review & editing (supporting)
Search for more papers by this authorEmmanuel Curis
Laboratoire de Biomathématiques, EA 7537 “BioSTM”, Faculté de Pharmacie, Université de Paris, Paris, France
Service de Biostatistiques et d'Information Médicale, Hôpital Saint-Louis, APHP, Paris, France
Contribution: Formal analysis (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJulien Dumurgier
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Contribution: Data curation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJacques Hugon
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Cognitive Neurology Center, APHP, Saint-Louis Lariboisière Fernand-Widal Hospital Group, Paris, France
Contribution: Conceptualization (supporting), Data curation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorClaire Paquet
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Cognitive Neurology Center, APHP, Saint-Louis Lariboisière Fernand-Widal Hospital Group, Paris, France
Contribution: Conceptualization (supporting), Data curation (equal), Writing - review & editing (supporting)
Search for more papers by this authorKarim Farid
Department of Nuclear Medicine, CHU French West Indies, Fort-de-France, France
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Contribution: Conceptualization (lead), Methodology (equal), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Jean-Claude Baron
Department of Neurology, Sainte-Anne Hospital, Université de Paris, Paris, France
INSERM U1266: Institut de Psychiatrie et Neurosciences de Paris, Université de Paris, Paris, France
Correspondence
Jean-Claude Baron, Department of Neurology, Sainte-Anne Hospital, Université de Paris, Paris, France.
Email: [email protected]
Contribution: Conceptualization (lead), Formal analysis (equal), Funding acquisition (lead), Methodology (lead), Project administration (equal), Supervision (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorSébastien Bergeret
Department of Nuclear Medicine, CHU French West Indies, Fort-de-France, France
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (equal)
Search for more papers by this authorMathieu Queneau
Department of Nuclear Medicine, Centre Cardiologique du Nord, Saint-Denis, France
Contribution: Data curation (equal), Writing - review & editing (supporting)
Search for more papers by this authorMathieu Rodallec
Department of Radiology, Centre Cardiologique du Nord, Saint-Denis, France
Contribution: Data curation (equal), Writing - review & editing (supporting)
Search for more papers by this authorEmmanuel Curis
Laboratoire de Biomathématiques, EA 7537 “BioSTM”, Faculté de Pharmacie, Université de Paris, Paris, France
Service de Biostatistiques et d'Information Médicale, Hôpital Saint-Louis, APHP, Paris, France
Contribution: Formal analysis (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJulien Dumurgier
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Contribution: Data curation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJacques Hugon
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Cognitive Neurology Center, APHP, Saint-Louis Lariboisière Fernand-Widal Hospital Group, Paris, France
Contribution: Conceptualization (supporting), Data curation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorClaire Paquet
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Cognitive Neurology Center, APHP, Saint-Louis Lariboisière Fernand-Widal Hospital Group, Paris, France
Contribution: Conceptualization (supporting), Data curation (equal), Writing - review & editing (supporting)
Search for more papers by this authorKarim Farid
Department of Nuclear Medicine, CHU French West Indies, Fort-de-France, France
INSERM UMR-S 1144: Therapeutic Optimization in Neuropsychopharmacology, Université de Paris, Paris, France
Contribution: Conceptualization (lead), Methodology (equal), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Jean-Claude Baron
Department of Neurology, Sainte-Anne Hospital, Université de Paris, Paris, France
INSERM U1266: Institut de Psychiatrie et Neurosciences de Paris, Université de Paris, Paris, France
Correspondence
Jean-Claude Baron, Department of Neurology, Sainte-Anne Hospital, Université de Paris, Paris, France.
Email: [email protected]
Contribution: Conceptualization (lead), Formal analysis (equal), Funding acquisition (lead), Methodology (lead), Project administration (equal), Supervision (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorKarim Farid and Jean-Claude Baron share senior authorship.
Abstract
Background
Cerebral amyloid angiopathy (CAA) is a frequent cause of both intracerebral hemorrhage (ICH) and cognitive impairment in the elderly. Diagnosis relies on the Boston criteria, which use magnetic resonance imaging markers including ≥2 exclusively lobar cerebral microbleeds (lCMBs). Although amyloid positron emission tomography (PET) may provide molecular diagnosis, its specificity relative to Alzheimer's disease (AD) is limited due to the prevalence of positive amyloid PET in cognitively normal elderly. Using early-phase 11C-Pittsburgh compound B as surrogate for tissue perfusion, a significantly lower occipital/posterior cingulate (O/PC) tracer uptake ratio in probable CAA relative to AD was recently reported, consistent with histopathological lesion distribution. We tested whether this finding could be reproduced using [18F]fluorodeoxyglucose (FDG)-PET, a widely available modality that correlates well with early-phase amyloid PET in both healthy subjects and AD.
Methods
From a large memory clinic database, we retrospectively included 14 patients with probable CAA (Boston criteria) and 21 patients with no lCMB fulfilling AD criteria including cerebrospinal fluid biomarkers. In all, [18F]FDG-PET/computed tomography (CT) was available as part of routine care. No subject had a clinical history of ICH. Regional standardized [18F]FDG uptake values normalized to the pons (standard uptake value ratio [SUVr]) were obtained, and the O/PC ratio was calculated.
Results
The SUVr O/PC ratio was significantly lower in CAA versus AD (1.02 ± 0.14 vs. 1.19 ± 0.18, respectively; p = 0.024).
Conclusions
Despite the small sample, our findings are consistent with the previous early-phase amyloid PET study. Thus, [18F]FDG-PET may help differentiate CAA from AD, particularly in cases of amyloid PET positivity. Larger prospective studies, including in CAA-related ICH, are however warranted.
CONFLICT OF INTEREST
None.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1Boulouis G, Charidimou A, Greenberg SM. Sporadic cerebral amyloid angiopathy: pathophysiology, neuroimaging features, and clinical implications. Semin Neurol. 2016; 36: 233-243.
- 2Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010; 9: 689-701.
- 3van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010; 9: 167-176.
- 4Arvanitakis Z, Leurgans SE, Wang Z, Wilson RS, Bennett DA, Schneider JA. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol. 2011; 69: 320-327.
- 5Banerjee G, Wilson D, Ambler G, et al. Cognitive impairment before intracerebral hemorrhage is associated with cerebral amyloid angiopathy. Stroke. 2018; 49: 40-45.
- 6Case NF, Charlton A, Zwiers A, et al. Cerebral amyloid angiopathy is associated with executive dysfunction and mild cognitive impairment. Stroke. 2016; 47: 2010-2016.
- 7Xiong L, Davidsdottir S, Reijmer YD, et al. Cognitive profile and its association with neuroimaging markers of non-demented cerebral amyloid angiopathy patients in a stroke unit. J Alzheimers Dis. 2016; 52: 171-178.
- 8Banerjee G, Carare R, Cordonnier C, et al. The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice. J Neurol Neurosurg Psychiatry. 2017; 88: 982-994.
- 9Arima H, Tzourio C, Anderson C, et al. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the progress trial. Stroke. 2010; 41: 394-396.
- 10Block F, Dafotakis M. Cerebral amyloid angiopathy in stroke medicine. Dtsch Arztebl Int. 2017; 114: 37-42.
- 11Charidimou A, Karayiannis C, Song TJ, et al. Brain microbleeds, anticoagulation, and hemorrhage risk: meta-analysis in stroke patients with AF. Neurology. 2017; 89: 2317-2326.
- 12Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010; 74: 1346-1350.
- 13Charidimou A, Boulouis G, Pasi M, et al. MRI-visible perivascular spaces in cerebral amyloid angiopathy and hypertensive arteriopathy. Neurology. 2017; 88: 1157-1164.
- 14Sharma R, Dearaugo S, Infeld B, O'Sullivan R, Gerraty RP. Cerebral amyloid angiopathy: review of clinico-radiological features and mimics. J Med Imaging Radiat Oncol. 2018. https://doi.org/10.1111/1754-9485.12726
- 15Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004; 55: 306-319.
- 16Lockhart A, Lamb JR, Osredkar T, et al. PIB is a non-specific imaging marker of amyloid-beta (abeta) peptide-related cerebral amyloidosis. Brain. 2007; 130: 2607-2615.
- 17Baron JC, Farid K, Dolan E, et al. Diagnostic utility of amyloid PET in cerebral amyloid angiopathy-related symptomatic intracerebral hemorrhage. J Cereb Blood Flow Metab. 2014; 34: 753-758.
- 18Farid K, Charidimou A, Baron JC. Amyloid positron emission tomography in sporadic cerebral amyloid angiopathy: a systematic critical update. Neuroimage Clin. 2017; 15: 247-263.
- 19Roberts RO, Aakre JA, Kremers WK, et al. Prevalence and outcomes of amyloid positivity among persons without dementia in a longitudinal, population-based setting. AMA Neurol. 2018; 75: 970-979.
- 20Charidimou A, Farid K, Baron JC. Amyloid-PET in sporadic cerebral amyloid angiopathy: a diagnostic accuracy meta-analysis. Neurology. 2017; 89: 1490-1498.
- 21Charidimou A, Farid K, Tsai HH, Tsai LK, Yen RF, Baron JC. Amyloid-PET burden and regional distribution in cerebral amyloid angiopathy: a systematic review and meta-analysis of biomarker performance. J Neurol Neurosurg Psychiatry. 2018; 89: 410-417.
- 22Farid K, Hong YT, Aigbirhio FI, et al. Early-phase 11c-PiB PET in amyloid angiopathy-related symptomatic cerebral hemorrhage: potential diagnostic value? PLoS ONE. 2015; 10:e0139926.
- 23Vinters HV, Gilbert JJ. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke. 1983; 14: 924-928.
- 24Rosand J, Muzikansky A, Kumar A, et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol. 2005; 58: 459-462.
- 25Bunai T, Kakimoto A, Yoshikawa E, Terada T, Ouchi Y. Biopathological significance of early-phase amyloid imaging in the spectrum of Alzheimer's disease. J Alzheimers Dis. 2019; 69: 529-538.
- 26Daerr S, Brendel M, Zach C, et al. Evaluation of early-phase [(18)F]-florbetaben PET acquisition in clinical routine cases. Neuroimage Clin. 2017; 14: 77-86.
- 27Forsberg A, Engler H, Blomquist G, Langstrom B, Nordberg A. The use of PIB-PET as a dual pathological and functional biomarker in ad. Biochim Biophys Acta. 2012; 1822: 380-385.
- 28Rostomian AH, Madison C, Rabinovici GD, Jagust WJ. Early 11c-PIB frames and 18F-FDG PET measures are comparable: a study validated in a cohort of AD and FTLD patients. J Nucl Med. 2011; 52: 173-179.
- 29Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014; 13: 614-629.
- 30Jack CR Jr, Bennett DA, Blennow K, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016; 87: 539-547.
- 31Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992; 55: 967-972.
- 32Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 t in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987; 149: 351-356.
- 33Bermejo-Guerrero L, Sanchez-Tejerina D, Sanchez-Tornero M, et al. Low amyloid-PET uptake in Iowa-type cerebral amyloid angiopathy with cerebral venous thrombosis. J Alzheimers Dis. 2019; 72: 677-681.
- 34Clergue-Duval V, Questel F, Azuar J, et al. Brain 18FDG-PET pattern in patients with alcohol-related cognitive impairment. Eur J Nucl Med Mol Imaging. 2020; 47: 281-291.
- 35Finnsson J, Lubberink M, Savitcheva I, et al. Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy. Acta Neurol Scand. 2019; 139: 135-142.
- 36Josephs KA, Duffy JR, Strand EA, et al. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech. Brain. 2012; 135: 1522-1536.
- 37Pasi M, Marini S, Morotti A, et al. Cerebellar hematoma location: implications for the underlying microangiopathy. Stroke. 2018; 49: 207-210.
- 38Kalpouzos G, Chetelat G, Baron JC, et al. Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging. 2009; 30: 112-124.
- 39Petit-Taboue MC, Landeau B, Desson JF, Desgranges B, Baron JC. Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping. NeuroImage. 1998; 7: 176-184.
- 40Sepehry AA, Lang D, Hsiung GY, Rauscher A. Prevalence of brain microbleeds in Alzheimer disease: a systematic review and meta-analysis on the influence of neuroimaging techniques. AJNR Am J Neuroradiol. 2016; 37: 215-222.
- 41Charidimou A, Frosch MP, Al-Shahi Salman R, et al. Advancing diagnostic criteria for sporadic cerebral amyloid angiopathy: study protocol for a multicenter MRI-pathology validation of Boston criteria v2.0. Int J Stroke. 2019; 14: 956-971.
- 42Greenberg SM, Charidimou A. Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. Stroke. 2018; 49: 491-497.
- 43McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34: 939-944.
- 44Keage HA, Carare RO, Friedland RP, et al. Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol. 2009; 9: 3.
- 45Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience, part xv. Neurology. 1996; 46: 1592-1596.
- 46Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol. 2011; 70: 871-880.
- 47Samuraki M, Matsunari I, Yoshita M, et al. Cerebral amyloid angiopathy-related microbleeds correlate with glucose metabolism and brain volume in Alzheimer's disease. J Alzheimers Dis. 2015; 48: 517-528.
- 48Atri A, Locascio JJ, Lin JM, et al. Prevalence and effects of lobar microhemorrhages in early-stage dementia. Neurodegener Dis. 2005; 2: 305-312.
- 49Sheikh-Bahaei N, Manavaki R, Sajjadi SA, Priest AN, O'Brien JT, Gillard JH. Correlation of lobar cerebral microbleeds with amyloid, perfusion, and metabolism in Alzheimer's disease. J Alzheimers Dis. 2019; 68: 1489-1497.
