Navegando por Palavras-chave "alzheimer disease"

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    Farmacogenética dos moduladores do metabolismo cerebrovascular na síndrome demencial da doença de alzheimer
    (Universidade Federal de São Paulo (UNIFESP), 2014-10-31) Oliveira, Fabricio Ferreira de [UNIFESP]; Bertolucci, Paulo Henrique Ferreira Bertolucci [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective: The aim of this study consisted on the investigation of risk factors for cognitive and functional decline of patients with Alzheimer?s disease dementia, as well as on the pharmacogenetic analysis of centrally and peripherally acting angiotensinconverting enzyme inhibitors, angiotensin receptor blockers and lipophilic statins, taking into account APOE haplotypes in addition to genotypes and haplotypes of ACE, CETP, LDLR, and the LXR-? gene (intron 2). Methods: Comparative analysis of neuropsychiatric and functional evolution of patients with the diagnosis of Alzheimer?s disease dementia throughout one year, taking into account schooling, age at onset of dementia, body mass index, coronary heart disease risk, gender, pharmacological treatment and APOE haplotypes, as well as genotypes and haplotypes of ACE, CETP, LDLR, and of the intron 2 of the LXR-? gene. Results: For a total of 193 patients, there was significant decline in cognition and functionality throughout one year, with no impact over caregiver distress. Nevertheless, levels of independence in activities of daily living did not necessarily follow variations in cognitive scores. For all patients, age at onset of dementia was the most important risk factor for faster cognitive and functional decline, while late life coronary heart disease risk was inversely related with cognitive decline only for carriers of APOE4+ haplotypes. Schooling was protective against cognitive decline only for women and carriers of APOE4+ haplotypes, while higher body mass index in late life was protective against cognitive decline only for men. Genotypes of CETP and LDLR that had traditionally been associated with higher risk of Alzheimer?s disease dementia were associated with later onset of the dementia syndrome. Carriers of the APOE-?4/?4 haplotype had earlier onset of dementia, besides faster worsening of CDR sum-of-boxes scores when they used lipophilic statins, and vice-versa. In general, patients with genetic propensity for faster cognitive and functional decline had maximum benefits when they used lipophilic statins, and vice-versa. For all patients, lipophilic statins slowed the worsening of independence in activities of daily living, while angiotensin-converting enzyme inhibitors caused a 50% reduction in Mini-Mental State Examination score change. Angiotensin-converting enzyme inhibitors improved the instrumental functionality of carriers of the APOE-?4/?4 haplotype. Angiotensin receptor blockers had genetically mediated effects that led to faster cognitive and functional decline. Angiotensin-converting enzyme inhibitors as a whole had more benefits than centrally-acting angiotensin-converting enzyme inhibitors only. Conclusions: Angiotensin-converting enzyme inhibitors seem to have Alzheimer?s disease modifying properties, while the effects of lipophilic statins seem to depend on specific genotypes for improvement or worsening of cognition and functionality, and angiotensin receptor blockers may worsen cognitive and functional decline.