RESUMO
Mutations in the presenilin 1 (PSEN1) gene are known to cause nearly 50% of early-onset, familial Alzheimer's disease (AD) cases. To determine whether E318G mutation is related causally to AD in the Polish population E318G mutation frequency was assessed using PCR-RFLP method in a total of 659 subjects: 256 AD patients, 210 healthy, age-matched control subjects, 100 Parkinson's disease patients and 93 centenarians. When the mutation frequencies were compared to healthy controls, no significant differences between the groups were found. It could be concluded that E318G mutation is not related causally to AD in the Polish population, either as a risk factor or a disease causing mutation.
Assuntos
Doença de Alzheimer/genética , Proteínas de Membrana/genética , Mutação Puntual , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Frequência do Gene , Ácido Glutâmico/genética , Glicina/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Polônia , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Presenilina-1RESUMO
BACKGROUND AND PURPOSE: The aim of the work was to investigate the effect of treatment with rivastigmine, one of the inhibitors of acetylcholinesterase (AChE-I) on the regional cerebral perfusion (rCBF) and the cognitive functions of the brain in patients with Alzheimer's Disease (AD) and Vascular Dementia (VaD). MATERIAL AND METHODS: The investigations of rCBF were carried out using SPECT (Single Photon Emission Computed Tomography). The results given concern investigations of patients carried out at the onset of the investigation, after 12 months, and 24 months of rivastigmine treatment. RESULTS: In patients with AD it was found that treatment with rivastigmine increases rCBF by 5-7% in the temporal areas during the first 12 months. In the frontal areas the increase was by 3-5%. During the next 12 months rCBF with an accuracy of 2% returned to the initial level, with the exception of the motor cortex, where it remained on the level increased by 5-6%. However, the cognitive functions remained constant during the first 12 months of treatment and decreased significantly during the next 12 months. In patients with VaD rCBF increased in all the regions of the brain except for the temporal posterior regions, and remained at an elevated level for the next 12 months. The cognitive functions deteriorated slowly, but to a much lesser degree than in the case of AD. CONCLUSIONS: From the investigations carried out it follows that treatment with rivastigmine during 24 months prevents a decrease of rCBF in patients with AD. However, the cognitive functions deteriorate after 24 months.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Demência Vascular/tratamento farmacológico , Fenilcarbamatos/uso terapêutico , Idoso , Doença de Alzheimer/fisiopatologia , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Cognição/efeitos dos fármacos , Demência Vascular/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Fenilcarbamatos/farmacologia , Rivastigmina , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Mutations in three causative genes have been identified in patients with an autosomal-dominant form of early-onset Alzheimer's disease (EOAD). To determine the spectrum of mutations in a group consisting of 40 Polish patients with clinically diagnosed familial EOAD and 1 patient with mild cognitive impairment (MCI) and family history of AD, we performed a screening for mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) genes. Four previously recognized pathogenic mutations in PSEN1 gene (H163R, M139V) and APP gene (T714A, V715A), and three novel putative mutations in PSEN1 gene (P117R and I213F) and PSEN2 gene (Q228L) were identified. The 34 patients with no mutations detected were older than the patients with mutations. A frequency of APOE4 allele was higher in this group. Frequency of mutations is relatively low (17%), possibly due to used operational definition of a patient with familial EOAD (a patient having at least one relative with early-onset dementia). It could be concluded that screening for mutations in the three genes could be included in a diagnostic program directed at patients with a positive family history or age of onset before 55 years.