Cerebrovascular risk factors in Alzheimer's disease: brain hemodynamics and pharmacogenomic implications.

Abstract:

:Recent evidence indicates that different vascular risk factors are present in Alzheimer's disease (AD) and other prevalent dementia types probably contributing to deterioration of cerebrovascular function, thus enhancing neurodegeneration and premature neuronal death due to a reduction in brain perfusion. Brain blood flow shows a reduced velocity and increased pulsatility (PI) and resistance indices (RI) in different types of dementia and in diabetes and hypertension, as well. High levels of diastolic blood pressure correlate with diminished brain blood flow and elevated PI and RI, accompanied by cognitive deterioration. Nitric oxide (NO) levels are found increased in the sera and brain tissue of AD patients. Vascular risk factors (hyperglycemia, LDL-cholesterol, triglycerides, hypertension) and altered brain hemodynamic parameters correlate with APOE genotypes of which APOE-4/4 carriers represent the AD population with the highest cerebrovascular risk. In addition, the genomic profiles of patients with dementia integrating AD-related genes (APOE, PS1, PS2, cFOS) in a mini-tetragenic haplotype significantly differ from controls with an absolute genetic variation of about 50%-60%. Cerebrovascular dysfunction is a factor common to most types of dementia; however, genetic variation among different dementia types might be determinant for the activation of early vascular events inducing or accelerating neurodegeneration. In this regard, cerebrovascular dysfunction should be considered a potential therapeutic target in dementia.

journal_name

Neurol Res

journal_title

Neurological research

authors

Cacabelos R,Fernández-Novoa L,Lombardi V,Corzo L,Pichel V,Kubota Y

doi

10.1179/016164103101202002

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

567-80

issue

6

eissn

0161-6412

issn

1743-1328

journal_volume

25

pub_type

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