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O1‐05‐01: Structural requirements for APP processing by γ ‐secretase
Author(s) -
KienlenCampard Pascal,
Constantinescu Stefan N.,
Tasiaux Bernadette,
Van Hees Joanne,
Ben Khalifa Naouel,
Huysseune Sandra,
Verslype Antoine,
Sato Takeshi,
Tang Tuchun,
Smith Steven O.,
Ocatve JeanNoël
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.223
Subject(s) - transmembrane domain , proteolysis , transmembrane protein , mutant , amyloid precursor protein , cleavage (geology) , biophysics , microbiology and biotechnology , biology , biochemistry , chemistry , gene , enzyme , alzheimer's disease , medicine , paleontology , receptor , disease , pathology , fracture (geology)
patients with mild to moderate Alzheimers disease (AD). Over a period of three years 233 AD patients, not treated with antidementive drugs before, were recruited by twelve university memory clinics. Methods: Outpatients with the diagnosis of probable AD according to the NINCDS-ADRDA criteria, presenting with a mild to moderate dementia syndrome and a MMSE score between 15-26 points at study entry, were treated for one year either with 24 mg galantamine CR alone or with a combination containing additionally 20 mg memantine. Patients with dementia any other type than AD, significant other neurological diseases, diagnosis of psychosis, history of epileptic seizures and any other acute or poorly controlled illness were excluded. Global severity of dementia was repetitively determined applying the CDR scale to monitor clinical progression of AD. Memory and cognitive performance were assessed using the ADAS-cog/11 at baseline, at sixteen weeks, six month and after twelve month. Additional parameters comprised the NPI to assess non-cognitive symptoms, the MADRS to measure depressive symptoms and the ADCS-ADL to assess the ability to perform activities of daily living. Results: The last patient completed the trial at the end of 2008 and the data bank will be closed early in 2009. Safety monitoring has already provided evidence that the combination regimen was well tolerated and severe unexpected side effects were lacking. Conclusions: At the conference data will be presented elucidating the primary objective that a combination therapy in AD patients improves memory or cognitive performance to a larger extent than galantamine alone.