Estudo dos fatores psicossociais, comorbidades clínicas e polimorfismos funcionais dos genes BDNF, COMT, 5HTT e APOE no binômio depressão-demência no idoso

Abstract

Alzheimer's disease (AD) and major depressive disorders are highly prevalent diseases in the population with high rates of disability. These two diseases are closely related and previous studies suggest that depression, particularly late-onset depression, may represent a risk factor for AD or an early manifestation of disease. Depression and AD usually have comorbidities associated with vascular risk factors such as diabetes mellitus (DM), dyslipidemia, hypertension (HBP) and coronary artery disease. AD and depression are complex diseases that involve multiple causes. Several polymorphisms seem to be implicated in the pathophysiology of both diseases. The only polymorphism unquestionably involved with the AD is the APOE 4. However, several studies suggest the involvement of other genes in AD. Because it is a disease whose treatment is still very inefficient, with high cost and significant side effects, and the fact that affects a significant number of elderly individuals, determining irreversible disability, it is necessary to clarify the mechanisms involved in its etiology and disease progression. We conducted a cross-sectional study involving 406 elderly divided into control group (97 subjects), AD without behavioral and psychological symptoms of dementia (BPSD) (75 subjects), DA with BPSD (94 individuals), late onset depression (140 patients). We analyzed the socio-demographic and clinical co-variables, as well as genotyping of functional polymorphisms of BDNF, APOE, COMT and 5-HTTLPR genes. We analyzed allele frequencies, genotypes, haplotypes and interactions between genes by comparing the three groups of patients with the control group. Our results showed an association between female sex and the two diseases; between low schooling and DA; smoking DA and depression; a strong association between AD and depression; diabetes and dyslipidemia were correlated only with AD with BPSD. The APOE4 was strongly associated with the diagnosis of AD with and without BPSD and earlier age of onset. We observed that depression is associated with the Met allele of rs6265 and showed synergistic interaction between 5-HTTLPR and rs4680. There was an association between DA and rs6265 and rs429358 and only a tendency for synergism (not statistically significant) between rs6265 and rs7124442. Psychosocial factors were associated with AD with BPSD and late onset depression. This study allows us to correlate some socio-demographic, psychosocial, genetic and clinical data involved in depression-dementia in the elderly.