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P2–405: Achei efficacy in familial Alzheimer's disease

2006; Wiley; Volume: 2; Issue: 3S_Part_12 Linguagem: Inglês

10.1016/j.jalz.2006.05.1246

1552-5279

Gianfranco Puccio, Rosanna Colao, Francesca Frangipane, Sabrina A.M. Curcio, Maria Mirabelli, Livia Bernardi, Carmine Tomaino, Nicoletta Smirne, Amalia C. Bruni,

Cholinesterase and Neurodegenerative Diseases

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no causative therapies are available. Acetylcholinesterase inhibitors (ACheEIs) are the current symptomatic approach largely used to enhance cholinergic function and hence cognitive performances. Nevertheless, drug response shows a large variability and is poorly predictable. It probably relies on the AD great genetic and phenotypic heterogeneity. 30% of AD cases display familiarity and 5% is caused by genes mutations. AD is particularly aggressive showing early onset and brief duration in the Calabrian families segregating PS1–Met146Leu mutation. To date, no studies on AChEis efficacy have been performed taking into account the presence of genes mutations and more generally the familiarity for AD. To evaluate AChEis response in a group of familial AD patients (with and without PS1Met146Leu) and to individuate possible predictors of response. Forty AD patients with familiarity (16 males, 24 females; mean age at onset 60.4+14,2 range 33–83) were diagnosed through NINCDS–ADRDA criteria, neuropsychological and neuroradiological assessment. Ten belonged to a PS1–Met146Leu family; 30 were familial cases not mutated (FADnm) whose familiarity was established through history. MMSE score measured degree of cognitive decline at T0, T3, T9, T15, T21 and T27 months. T0 was at about 4 years from onset, MMSE value at T0 was 15.6+3.7. Inquired predictors were: sex, education, age at onset, rate progression, MMSE score at T0, APOE4+, PS1 Met146Leu+, CYP46 polymorphism. Pearson/Spearman and the single t–test were used to compare to the expected decline (4.4 points for year). All patients had a good response to AchEI: MMSE score improved of 1.3 point in mean at T3 (p=0.001) and patients maintained cognitive benefit up to 27 months (p=0.000). No predictors of drug response were identified. When stratified dataset for PS1 Met146Leu we observed that genetic patients were the worst responders in mean (at T3, MMSE score difference was not significant) but response was highly individual: T3 score varying from +4 to –2. We demonstrate a favourable effect of AChEIs in familial AD patients more evident in patients without genetic mutations. The genetic group efficacy was individual and not predictable.