Klinischer Nutzen nuklearmedizinischer Verfahren in der Demenzdiagnostik

Zusammenfassung

Eine sichere Diagnose neurodegenerativer Demenzerkrankungen kann nur mittels post mortem histopathologischer Evaluation des Gehirngewebes erfolgen. Es ist akzeptiert, dass die pathologischen Veränderungen Jahre bis Jahrzehnte vor Beginn der klinischen Symptomatik einsetzen. Der Nutzen klinischneuropsychologischer Maße für die frühe Diagnostik dieser Erkrankungen im vor- oder geringsymptomatischen Stadium ist somit limitiert. Die zum Teil deutliche symptomatische Überlappung unterschiedlicher Demenzerkrankungen erschwert zusätzlich die klinische Differenzialdiagnostik. Insbesondere neue Therapieansätze machen aber eine frühe und zuverlässige Differenzialdiagnose immer wichtiger, was den Bedarf an geeigneten Biomarkern unterstreicht. Hier sollen zwei Verfahren der molekularen und funktionellen Bildgebung behandelt werden, die vielversprechend und gut evaluiert sind: Die FDGPET (Positronen Emissions Tomografie) als Marker der regionalen neuronalen Dysfunktion. Und die Amyloidplaquebildgebung mittels moderner PET-Tracer wie dem PIB. Deren Wertigkeit in der Früh- und Differenzialdiagnostik sowie für die Patientenselektion für Therapiestudien und für eine objektive Therapiekontrolle wird diskutiert.

Summary

So far, a definite diagnosis of different forms of neurodegenerative dementias can only be carried out by post-mortem histopathological evaluation of brain tissue. It is accepted that the pathological changes in the brain start years to decades ahead of the onset of clinical symptoms. The utility of clinical/neuropsychological test measures for early diagnosis of these disorders in mild or asymptomatic stages is therefore limited. Additionally, the symptomatic overlap between different forms of dementia hampers clinical differential diagnosis. Particularly new treatment approaches constitute the need for reliable early and differential diagnosis, which underlines the need for suitable biomarkers. Here, we will discuss the value of two functional/ molecular imaging procedures, which are most promising and well-evaluated for this purpose FDG PET (positron emission tomography) as a measure of neuronal dysfunction and amyloid- plaque imaging using modern PET tracer such as PIB. The value of these imaging tools for early and differential diagnosis as well as for patient selection for therapy studies and for objective therapy control will be discussed.

Schlüsselwörter

PET - FDG - PIB - Demenz - Alzheimer

Keywords

PET - FDG - PIB - dementia - Alzheimer’s disease

• Literatur

• 1 Aizenstein HJ. et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 2008; 65 (Suppl. 11) 1509-17.
• 2 Alafuzoff I. The pathology of dementias: an overview. Acta Neurol Scand Suppl 1992; 139: 8-15.
• 3 Alexander GE. et al. Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer’s disease treatment studies. Am J Psychiatry 2002; 159 (Suppl. 05) 738-45.
• 4 Arnaiz E. et al. Mild cognitive impairment: a crossnational comparison. J Neurol Neurosurg Psychiatry 2004; 75 (Suppl. 09) 1275-80.
• 5 Arnaiz E. et al. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport 2001; 12 (Suppl. 04) 851-5.
• 6 Bickel H. [Dementia syndrome and Alzheimer disease: an assessment of morbidity and annual incidence in Germany]. Gesundheitswesen 2000; 62 (Suppl. 04) 211-8.
• 7 Boyle A. et al. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology 2006; 67 (Suppl. 03) 441-5.
• 8 Braak E. et al. Neuropathology of Alzheimer’s disease: what is new since A. Alzheimer?. Eur Arch Psychiatry Clin Neurosci 1999; 249 (Suppl. 03) 14-22.
• 9 Bundesministerium für Umwelt, N.u.R.. Jahresbericht: Umweltradioaktivität und Strahlenbelastung; 2006
• 10 Catana C. et al. Simultaneous acquisition of multislice PET and MR images: initial results with a MRcompatible PET scanner. J Nucl Med 2006; 47 (Suppl. 12) 1968-76.
• 11 Chetelat G. et al. Mild cognitive impairment: Can FDG-PET predict who is to rapidly convert to Alzheimer’s disease?. Neurology 2003; 60 (Suppl. 08) 1374-7.
• 12 Davies RR. et al. The pathological basis of semantic dementia. Brain 2005; 128 (Suppl. 09) 1984-95.
• 13 de Leon J. et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro- 2-deoxy-D-glucose/poitron-emission tomography (FDG/PET). Proc Natl Acad Sci USA 2001; 98 (Suppl. 19) 10966-71.
• 14 Devanand D. et al. Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology 2007; 68 (Suppl. 11) 828-36.
• 15 Diehl-Schmid J. et al. Longitudinal changes of cerebral glucose metabolism in semantic dementia. Dement Geriatr Cogn Disord 2006; 22 (Suppl. 04) 346-51.
• 16 Diehl-Schmid J. et al. Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study. Neurobiol Aging 2007; 28 (Suppl. 01) 42-50.
• 17 Drzezga A. Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 01) S4-11.
• 18 Drzezga A. et al. Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. Neurology 2009; 72 (Suppl. 17) 1487-94.
• 19 Drzezga A. et al. Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease. Neuroimage 2008; 39 (Suppl. 02) 619-33.
• 20 Drzezga A. et al. Prediction of individual clinical outcome in MCI by means of genetic assessment and 18F-FDG PET. J Nucl Med 2005; 46 (Suppl. 10) 1625-32.
• 21 Drzezga A. et al. Prominent hypometabolism of the right temporoparietal and frontal cortex in two lefthanded patients with primary progressive aphasia. J Neurol 2002; 249 (Suppl. 09) 1263-7.
• 22 Drzezga A. et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 2003; 30 (Suppl. 08) 1104-13.
• 23 Engler H. et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006; 129 (Suppl. 11) 2805-7.
• 24 Engler H. et al. In vivo amyloid imaging with PET in frontotemporal dementia. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 01) 100-6.
• 25 Fleisher AS. et al. Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment. Neurology 2008; 70 (Suppl. 03) 191-9.
• 26 Forsberg A. et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 2008; 29 (Suppl. 10) 1456-65.
• 27 Grimmer T. et al. Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 2009; 65 (Suppl. 11) 927-34.
• 28 Hardy JA, Higgins G. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992; 256 5054 184-5.
• 29 Henriksen G. et al. Development and evaluation of compounds for imaging of beta-amyloid plaque by means of positron emission tomography. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 01) S75-81.
• 30 Herholz K. FDG PET and differential diagnosis of dementia. Alzheimer Dis Assoc Disord 1995; 9 (Suppl. 01) 6-16.
• 31 Herholz K. PET studies in dementia. Ann Nucl Med 2003; 17 (Suppl. 02) 79-89.
• 32 Herholz K. et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 2002; 17 (Suppl. 01) 302-16.
• 33 Herholz K. et al. Direct comparison of spatially normalized PET and SPECT scans in Alzheimer’s disease. J Nucl Med 2002; 43 (Suppl. 01) 21-6.
• 34 Hoffman JM. et al. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med 2000; 41 (Suppl. 11) 1920-8.
• 35 Hull M, Berger M, Heneka M. Disease-modifying therapies in Alzheimer’s disease: how far have we come?. Drugs 2006; 66 (Suppl. 16) 2075-93.
• 36 Ibanez V. et al. Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer’s disease. Neurology 1998; 50 (Suppl. 06) 1585-93.
• 37 Ikeda M, Ishikawa T, Tanabe H. Epidemiology of frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 2004; 17 (Suppl. 04) 265-8.
• 38 Ikonomovic MD. et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 2008; 131 (Suppl. 06) 1630-45.
• 39 Ishii K. Clinical application of positron emission tomography for diagnosis of dementia. Ann Nucl Med 2002; 16 (Suppl. 08) 515-25.
• 40 Jack CR. et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 2008; 131 (Suppl. 03) 665-80.
• 41 Jack CR. et al. Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology 2005; 65 (Suppl. 08) 1227-31.
• 42 Johnson JK. et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol 2005; 62 (Suppl. 06) 925-30.
• 43 Kawachi T. et al. Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2006; 33 (Suppl. 07) 801-9.
• 44 Klunk WE. et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004; 55 (Suppl. 03) 306-19.
• 45 Klunk WE. et al. Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci 2007; 27 (Suppl. 23) 6174-84.
• 46 Knopman DS. et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 56 (Suppl. 09) 1143-53.
• 47 Leinonen V. et al. Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol 2008; 65 (Suppl. 10) 1304-9.
• 48 Li Y. et al. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 12) 2169-81.
• 49 Lim A. et al. Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 1999; 47 (Suppl. 05) 564-9.
• 50 Lockhar A. et al. PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain 2007; 130 (Suppl. 10) 2607-15.
• 51 Magistretti J, Pellerin L. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 1999; 354 1387 1155-63.
• 52 Matsunari I. et al. Comparison of 18F-FDG PET and optimized voxel-based morphometry for detection of Alzheimer’s disease: aging effect on diagnostic performance. J Nucl Med 2007; 48 (Suppl. 12) 1961-70.
• 53 McKeith I. et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007; 6 (Suppl. 04) 305-13.
• 54 McKeith IG. et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005; 65 (Suppl. 12) 1863-72.
• 55 McKhann G. et al. 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 (Suppl. 07) 939-44.
• 56 Minoshima S. Imaging Alzheimer’s disease: clinical applications. Neuroimaging Clin N Am 2003; 13 (Suppl. 04) 769-80.
• 57 Minoshima S. et al. Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol 2001; 50 (Suppl. 03) 358-65.
• 58 Minoshima S. et al. A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36 (Suppl. 07) 1238-48.
• 59 Minoshima S. et al. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 1997; 42 (Suppl. 01) 85-94.
• 60 Mintun M. et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 2006; 67 (Suppl. 03) 446-52.
• 61 Mormino EC. et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain 2009; 132 (Suppl. 05) 1310-23.
• 62 Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDGPET studies in MCI and AD. Eur J Nucl Med Mol Imaging 2005; 32 (Suppl. 04) 486-510.
• 63 Mosconi L. et al. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2009; 36 (Suppl. 05) 811-22.
• 64 Mosconi L. et al. MCI conversion to dementia and the APOE genotype: a prediction study with FDGPET. Neurology 2004; 63 (Suppl. 12) 2332-40.
• 65 Mosconi L. et al. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J Nucl Med 2006; 47 (Suppl. 11) 1778-86.
• 66 Mosconi L. et al. Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis. Neurology 2005; 64 (Suppl. 11) 1860-7.
• 67 Mosconi L. et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med 2008; 49 (Suppl. 03) 390-8.
• 68 Moulin-Romsee G. et al. Cost-effectiveness of 18F-fluorodeoxyglucose positron emission tomography in the assessment of early dementia from a Belgian and European perspective. Eur J Neurol 2005; 12 (Suppl. 04) 254-63.
• 69 Neary D. et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51 (Suppl. 06) 1546-54.
• 70 Nestor J, Fryer T, Hodges J. Declarative memory impairments in Alzheimer’s disease and semantic dementia. Neuroimage 2006; 30 (Suppl. 03) 1010-20.
• 71 Neumann M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314 5796 130-3.
• 72 Neurologie DGF. Leitlinien für Diagnostik und Therapie in der Neurologie; 4. Auflage. Stuttgart: Thieme Verlag; 2008
• 73 Ng S. et al. Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer’s disease. J Nucl Med 2007; 48 (Suppl. 04) 547-52.
• 74 Nobili F. et al. Principal component analysis of FDG PET in amnestic MCI. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 12) 2191-202.
• 75 Perneczky R. et al. Activities of daily living, cerebral glucose metabolism, and cognitive reserve in Lewy body and Parkinson’s disease. Dement Geriatr Cogn Disord 2008; 26 (Suppl. 05) 475-81.
• 76 Petersen R. et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56 (Suppl. 03) 303-8.
• 77 Phelps ME, Schelbert H, Mazziotta J. Positron computed tomography for studies of myocardial and cerebral function. Ann Intern Med 1983; 98 (Suppl. 03) 339-59.
• 78 Pike KE. et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 2007; 130 (Suppl. 11) 2837-44.
• 79 Price J. et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound- B. J Cereb Blood Flow Metab 2005; 25 (Suppl. 11) 1528-47.
• 80 Rabinovici GD. et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007; 68 (Suppl. 15) 1205-12.
• 81 Rabinovici GD. et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 2008; 64 (Suppl. 04) 388-401.
• 82 Reiman EM. et al. Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 1996; 334 (Suppl. 12) 752-8.
• 83 Reiman EM. et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA 2009; 106 (Suppl. 16) 6820-5.
• 84 Rowe CC. et al. Imaging beta-amyloid burden in aging and dementia. Neurology 2007; 68 (Suppl. 20) 1718-25.
• 85 Salmon E. et al. Differential diagnosis of Alzheimer’s disease with PET. J Nucl Med 1994; 35 (Suppl. 03) 391-8.
• 86 Selkoe DJ. Folding proteins in fatal ways. Nature 2003; 426 6968 900-4.
• 87 Selkoe DJ. Soluble oligomers of the amyloid betaprotein impair synaptic plasticity and behavior. Behav Brain Res 2008; 192 (Suppl. 01) 106-13.
• 88 Shi J. et al. Histopathological changes underlying frontotemporal lobar degeneration with clinico- pathological correlation. Acta Neuropathol (Berl) 2005; 110 (Suppl. 05) 501-12.
• 89 Silverman DH. et al. Evaluating early dementia with and without assessment of regional cerebral metabolism by PET: a comparison of predicted costs and benefits. J Nucl Med 2002; 43 (Suppl. 02) 253-66.
• 90 Silverman DH. et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. Jama 2001; 286 (Suppl. 17) 2120-7.
• 91 Stefanova E. et al. Longitudinal PET evaluation of cerebral glucose metabolism in rivastigmine treated patients with mild Alzheimer’s disease. J Neural Transm 2006; 113 (Suppl. 02) 205-18.
• 92 Thompson W. et al. Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer’s disease pathologies. J Neurochem 2009; 109 (Suppl. 02) 623-30.
• 93 Villemagne VL. et al. Abeta deposits in older nondemented individuals with cognitive decline are indicative of preclinical Alzheimer’s disease. Neuropsychologia 2008; 46 (Suppl. 06) 1688-97.
• 94 Waxman A. et al. Society of Nuclear Medicine Procedure Guideline for FDG PET Brain Imaging. Version 1.0. Society of Nuclear Medicine 2009
• 95 Weisman D. et al. In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution. Neurology 2007; 69 (Suppl. 04) 356-9.
• 96 Yuan Y, Gu Z, Wei WS. Fluorodeoxyglucose-positron- emission tomography, single-photon emission tomography, and structural MR imaging for prediction of rapid conversion to Alzheimer disease in patients with mild cognitive impairment: a meta-analysis. AJNR Am J Neuroradiol 2009; 30 (Suppl. 02) 404-10.
• 97 Zaccai J, McCracken C, Brayne C. A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 2005; 34 (Suppl. 06) 561-6.
• 98 Zamrini E, De Santi S, Tolar M. Imaging is superior to cognitive testing for early diagnosis of Alzheimer’s disease. Neurobiol Aging 2004; 25 (Suppl. 05) 685-91.
• 99 Tatsch K. et al. Klinischer Nutzen nuklearmedizinischer Verfahren in der Diagnostik von Bewegungsstörungen. Nervenheilkunde 2009; 28: 691-700.
• 100 Drzezga A. Amyloid plaque imaging in early and differential diagnosis in dementia. Ann Nucl Med. 2009 ; im Druck.