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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282X

Arq. Neuro-Psiquiatr. vol.73 no.3 São Paulo Mar. 2015

http://dx.doi.org/10.1590/0004-282X20140226 

THESE

Pharmacogenetics of cerebrovascular metabolism modulators in dementia due to Alzheimer’s disease

Farmacogenética dos moduladores do metabolismo cerebrovascular na síndrome demencial da doença de Alzheimer

Fabricio Ferreira de Oliveira1 

1Resumo da Tese de Doutorado apresentada à Escola Paulista de Medicina, Universidade Federal de São Paulo. Área de Neurologia e Neurociência. São Paulo SP, Brasil.

ABSTRACT

The aims of this study were to investigate risk factors for cognitive and functional decline among 193 patients with Alzheimer’s disease dementia (AD), and to conduct pharmacogenetic analysis on cerebrovascular metabolism modulators, taking into account APOE haplotypes and the genotypes of ACE, CETP, LDLR and the LXR-β gene. For all patients, later age at AD onset was the most important risk factor for faster cognitive and functional decline, while the late-life coronary heart disease risk was inversely related to 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. Carriers of the APOE-ε4/ε4 haplotype had earlier AD onset, whereas genotypes of CETP and LDLR that had traditionally been associated with higher risk of AD were associated with later onset of dementia. Angiotensin-converting enzyme inhibitors caused a 50% reduction in Mini-Mental State Examination score changes, and had better disease-modifying properties than did centrally-acting angiotensin-converting enzyme inhibitors alone. Angiotensin receptor blockers had genetically mediated effects that led to faster cognitive and functional decline, while patients with genetic tendencies towards faster cognitive and functional decline had maximum benefits when they used lipophilic statins, and vice versa.

Key words: Alzheimer disease; dementia; cerebrovascular disorders; neurodegenerative diseases; risk factors; pharmacogenetics; genetics

Received: October 20, 2014; Revised: November 06, 2014; Accepted: November 26, 2014

Correspondence: Fabricio Ferreira de Oliveira; Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia; Rua Botucatu, 740, Vila Clementino; 04023-900 São Paulo SP, Brasil; E-mail: fabricioferreiradeoliveira@hotmail.com

Supervisor: Paulo Henrique Ferreira Bertolucci (Departamento de Neurologia e Neurocirurgia).

Co-Supervisora: Marilia de Arruda Cardoso Smith (Departamento de Morfologia e Genética).

Support: CAPES – Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.