Navegando por Palavras-chave "cerebrovascular disorders"

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    Assessment of risk factors for earlier onset of sporadic Alzheimer's disease dementia
    (Medknow Publications & Media Pvt Ltd, 2014-11-01) Oliveira, Fabricio Ferreira de [UNIFESP]; Bertolucci, Paulo Henrique Ferreira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Smith, Marilia de Arruda Cardoso [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background: Pharmacological treatment has mild effects for patients with Alzheimer's disease dementia (AD); therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account the Framingham risk scoring as the sole measure of vascular risk. Subjects and Methods: We included 209 consecutive late-onset AD patients to find out which factors among educational levels, coronary heart disease risk estimated by way of Framingham risk scores, history of head trauma or depression, surgical procedures under general anesthesia, family history of neurodegenerative diseases, gender, marital status and APOE haplotypes might be related to the age of dementia onset in this sample of patients with low mean schooling. Results: Mean age of AD onset was 73.38 +/- 6.5 years old, unaffected by schooling or family history of neurodegenerative diseases. Patients who were APOE-epsilon 4 carriers, married, or with history of depression, had earlier onset of AD, particularly when they were women. Coronary heart disease risk was marginally significant for later onset of AD. Conclusions: APOE haplotypes, marital status and history of depression were the most important factors to influence the age of AD onset in this sample. While midlife cerebrovascular risk factors may increase incidence of AD, they may lead to later dementia onset when present in late life.
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    Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia
    (Assoc Brasileira Psiquiatria, 2017) de Oliveira, Fabricio F. [UNIFESP]; Chen, Elizabeth S. [UNIFESP]; Smith, Marilia C. [UNIFESP]; Bertolucci, Paulo H. [UNIFESP]
    Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs1 1669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121. Results: Considering 201 patients, only APOE-epsilon 4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs1 1669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.
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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.
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    Risk factors for age at onset of dementia due to Alzheimer's disease in a sample of patients with low mean schooling from São Paulo, Brazil
    (Wiley-Blackwell, 2014-10-01) Oliveira, Fabricio Ferreira de [UNIFESP]; Bertolucci, Paulo Henrique Ferreira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Smith, Marilia Cardoso [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective: in view of the mild effects of pharmacological treatment for dementia due to Alzheimer's disease (AD), the search for modifiable risk factors is an important challenge. Although risk factors for AD are widely recognized, elements that influence the time of onset of the dementia syndrome have not been comprehensively reported. We aimed to investigate which risk factors might be associated with the age at onset of AD in a sample of patients with low mean schooling from São Paulo, Brazil.Methods: We included 210 consecutive patients with late-onset AD to investigate whether education, gender, nationality, urban living and sanitation, occupation, cognitive and physical inactivity, head trauma, depression, systemic infections, surgical interventions, cerebrovascular risk factors, family history of neurodegenerative diseases or cardiovascular diseases and apolipoprotein E gene (APOE) haplotypes might be related to the age at AD onset.Results: Each copy of APOE-epsilon 4 led to onset of AD almost 2 years earlier, while depression, smoking, higher body mass index and family history of cardiovascular diseases were also highly significant. Protective factors included non-Brazilian nationality, use of a pacemaker and waist circumference. Cerebrovascular risk factors had a mild combined effect for earlier onset of AD.Conclusion: APOE haplotypes, depression, nationality and cerebrovascular risk factors were the most important elements to influence the age at AD onset in this sample, whereas gender, education, occupation and physical activities had no isolated effects over the age at onset of this dementia syndrome. Copyright (C) 2014 John Wiley & Sons, Ltd.