MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz

Zusammenfassung

Langfristig angelegte Studien sind notwendig um die präventive und frühtherapeutische Wirksamkeit von Interventionen im Vorfeld der Demenzmanifestation zu erfassen. Wegen des hohen Aufwands an Patienten und Untersuchungen, der erwartbar hohen drop-out Raten und der geringen klinischen Progression in den Gesamtstichproben, ist der Einsatz von Biomarkern von besonderem Interesse. Die Eignung funktioneller und auch struktureller Bildgebungsverfahren wird derzeit – mit ersten positiven Ergebnissen – geprüft; ob sich konventionelle Liquormarker der Alzheimer Krankheit wie beta-Amyloid und die Tau-Proteine als hinreichend veränderungssensitiv erweisen, um die Effekte früher Interventionen zu erfassen, erscheint fraglich. Auch muss offen bleiben, ob sich ähnliche Methoden in abgewandelter Form zum Einsatz in der Praxis eignen.

Abstract

Long-term studies will be pivotal in order to examine the efficacy of preventive and early therapeutic interventions during the preclinical phase of dementia. Biomarkers will be of importance due to the large sample sizes and the necessary logistic efforts, high drop-out rates and slow clinical progression. The validity of functional and even structural imaging methods is currently investigated with early and promising results; it is presently unclear whether conventional csf-markers of Alzheimer’s disease (beta-amyloid and tau-proteins) are sufficiently sensitive to monitor the effects of early interventions. It also remains doubtful whether modifications of these methods will ever be useful and available for practical purposes.

Schlüsselwörter

leichte kognitive Beeinträchtigung - MCI-plus - Neuropsychologie - Progression - Demenz - Morbus Alzheimer - Biomarker - Neuroimaging - CSF-Marker

Keywords

Mild cognitive impairment - MCI-plus - neuropsychology - progression - dementia - Alzheimer’s disease - biomarkers - neuroimaging - tau - beta-amyloid

Literatur

• 1 Apostolova L G, Dutton R A, Dinov I D. et al . Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps.  Arch Neurol. 2006;  63 693-9
• 2 Barrio J R, Kepe V, Satyamurthy N, Huang S C, Small G. Amyloid and tau imaging, neuronal losses and function in mild cognitive impairment.  J Nutr Health Aging. 2008;  12 61S-65
• 3 Bickel H, Mösch E, Seigerschmidt E, Siemen M, Förstl H. Prevalence and persistence of mild cognitive impairment among elderly patients in general hospitals.  Dement Geriatr Cogn Disord. 2006;  21 242-50
• 4 Brys M, Pirraglia E, Rich K. et al . Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.  Neurobiol Aging. 2007;  , Epub ahead of print
• 5 De Jager C A, Hogervorst E, Combrinck M, Budge M M. Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer’s disease.  Psychol Med. 2003;  33 1039-1050
• 6 Dickerson B C, Sperling R A. Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer’s disease: Insights from functional MRI studies.  Neuropsychologia. 2008;  46 (6) 1624-1635
• 7 Döbert N, Pantel J, Frölich L, Hamscho N, Menzel C, Grünwald F. Diagnostic value of FDG-PET and HMPAO-SPET in patients with early dementia and MCI: Metabolic index and perfusion index.  Dementia Geriat Cognitive Disord. 2005;  20 63-70
• 8 Förstl H, Bickel H, Frölich L. et al . Leichte kognitive Beeinträchtigung mit Vorzeichen rascher Verschlechterung.  Dtsch Med Wochenschr. 2007;  133 431-436
• 9 Förstl H, Gratz S, Hahn U, Schwarz J, Jarnig M. Demenz mit Lewy-Körperchen und verminderter Dopamin-Transporter-Bindung verweist auf Acetylcholin-Mangel.  Dtsch Med Wochenschr. 2008;  133, Suppl 1 S11-14
• 10 Förstl H, Hentschel F, Sattel H. et al . Age-associated memory impairment and early Alzheimer’s disease – only time will tell the difference.  Arzneimittel Forschung. 1995;  45 394-397
• 11 Fox N C, Black R S, Gilman S. et al . Effects of Aß-immunisation (AN1792) on MRI measures of cerebral volume in Alzheimer disease.  Neurology. 2005;  64 1563-1572
• 12 Greenaway M C, Lacritz L H, Binegar D. et al . Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.  Cog Behav Neurol. 2006;  19 79-84
• 13 Hahn U, Schwarz J, Gratz S. et al . Morphologische Magnetresonanztomographie: Ihre Wertigkeit bei der Diagnose neurodegenerativer Erkrankungen.  DMW. 2008;  133 S15-S18
• 14 Hashimoto M, Kazui H, Matsumoto K, Nakano Y, Yasuda M, Mori E. Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer’s disease?.  Am J Psychiat. 2005;  162 676-82
• 15 Jelic V. et al . Clinical trials in mild cognitive impairment: lessons for the future.  J Neurol Neurosurg Psychiat. 2006;  77 429-438
• 16 Jessen F, Traeber F, Freymann K, Maier W, Schild, HH, Block, W. Treatment monitoring and response prediction with proton MR spectroscopy in AD.  Neurology. 2006;  67 528-530
• 17 Luckhaus C, Flüb M O, Wittsack H J. et al . Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer’s dementia by perfusion-weighted magnetic resonance imaging.  Neuroimage. 2008;  40 495-503
• 18 Mix J A, Crews W D. A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761® in a sample of cognitively intact older adults: neuropsychological findings.  Hum Psychopharmacol Clin Exp. 2002;  17 267-277
• 19 Pike K E, Savage G, Villemagne V L. et al . Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease.  Brain. 2007;  130 2837-44
• 20 Pilatus U, Lais C, de Du Mesnil Rochmont A, Kratzsch T, Frölich L, Lanfermann H, Zanella F, Pantel J. Conversion to dementia in mild cognitive impairment is associated with decline of N-acetyl aspartate and creatine as revealed by MR-spectroscopy. Psychiatry Research: Neuroimaging (im Druck)
• 21 Raschetti R, Albanese E, Vanacore N, Maggini M. Cholinesterase inhibitors in mild cognitive impairment: A systematic review of randomised trials.  PLoS Med. 2007;  4 e338 , doi10.1371/ journal. pmed. 0040338
• 22 Ries M L, Carlsson C M, Rowley H A. et al . Magnetic resonance imaging characterization of brain structure and function in mild cognitive impairment: a review.  J Am Geriat Soc. 2008;  56 920-934
• 23 Sabri O, Kendziorra K, Wolf, H. et al . Acetylcholine receptors in dementia and mild cognitive impairment.  Europ J Nucl Med Mol Imaging. 2008;  35 S30-S45
• 24 Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F. Progression of leuko-araiosis and cognition.  Stroke. 2007;  38 2619-25
• 25 Schönknecht P, Pantel J, Kaiser E. et al . Increased tau protein differentiates mild cognitive impairment from geriatric depression and predicts conversion to dementia.  Neurosci Lett. 2007;  416 39-42
• 26 Shimizu S, Hanyu H, Iwamoto T, Koizumi K, Abe K. SPECT follow-up study of cerebral blood flow changes during Donepezil therapy in patients with Alzheimer’s disease.  J Neuroimaging. 2006;  16 16-23
• 27 Sorg C, Riedl V, Mühlau M. et al . Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease.  PNAS. 2007;  104 18760-65
• 28 Teipel S J, Drzezga A, Bartenstein P, Möller H J, Schwaiger M, Hampel H. Effects of donepezil on cortical metabolic response to activation during (18)FDG-PET in Alzheimer’s disease: a double-blind cross-over trial.  Psychopharmacology (Berl). 2006;  187 86-94
• 29 Twamley E W, Legendre Ropacki S A, Bondi M W. Neuropsychological and neuroimaging changes in preclinical Alzheimer’s disease.  J Int Neuropsychol Soc. 2006;  12 707-35
• 30 Vellas B, Andrieu S, Sampaio C, Wilcock G. for the EUROPEAN TASK FORCE GROUP . Disease Modifying Trials in Alzheimer’s Disease: A European Task Force Consensus.  Lancet Neurology. 2007;  6 56-62
• 31 Wolf H, Hensel A, Wahlund L O, Gertz H J. Structural correlates of mild cognitive impairment.  Neurobiol Aging. 2004;  25 913-924