Session Title: Alzheimer's Disease (AD) including Non-Cognitive Aspects
Presentation Date: Friday, March 14 – Saturday, March 15, 2009
A RAPIDLY PROGRESSIVE SUBTYPE OF ALZHEIMER´S DISEASE
C. Schmidt1, K. Redyk1, B. Meissner1, L. Krack1, N. von Ahsen2, S. Roeber3, H. Kretzschmar3, I. Zerr1
1University Hospital, Georg-August University Göttingen, Dep. of Neurology, Göttingen, Germany, 2University Hospital, Georg-August University Göttingen, Dep. of Clinical Chemistry, Göttingen, Germany, 3Hospital of the Ludwig-Maximilian University Munich, Dep. of Neuropathology, Munich, Germany
Objective: To characterize the clinical features as well as CSF biomarkers and genetic polymorphisms of patients suffering from a rapidly progressive subtype of Alzheimer´s dementia (rpAD).
Methods: Retrospective analyses of neuropathologically confirmed rpAD cases were performed. Those cases had been differentially diagnosed with AD out of a group with rapidly progressive dementia suspicious of Creutzfeldt-Jakob disease. Clinical features, biomarkers (CSF proteins 14-3-3, Tau protein, Amyloid beta 1-42) and genetic markers (PRNP Codon 129, Apo E polymorphism) were examined.
Results: Thirtytwo patients were identified. Median survival: 26 months, age at onset: 73 years. Mean CSF Amyloid beta 1-42: 266 pg/ml, median CSF Tau: 491 pg/ml, 31% positive for 14-3-3 proteins. Genetic polymorphisms were abnormal as compared to classical AD patients PRNP codon 129 methionine homozygosity being predominant. Frequency of the Apo E4 allele: 31%. No patient was homozygous for Apo E4. The frequency of 35 symptoms and their time point of occurrence are demonstrated. Frequent signs were myoclonus (75%), disturbed gait (66%) and rigidity (50%). Symptom manifestation dependant from PRNP gene codon 129 polymorphism was evaluated as well.
Interpretation: rpAD appears to be associated with a diversity of focal neurologic signs even able to mimick CJD. Physicians should be aware of this AD subtype´s existence as this knowledge aids the differential diagnostic process. It should be considered when revising criteria for the clinical diagnosis of AD. The distribution of genetic polymorphisms differ from those seen in classical AD types. These factors might modify the disease progression rate.