The main results of this study show: 1) morphological changes characterized by an increased carotid IMT and functional changes qualified as an increase in central SBP in hypertensive patients with CD; 2) Among the risk factors for the development of CD, the age, HDL cholesterol, LDL cholesterol, triglycerides and increased IMT were significantly associated with a drop in MMSE scores in hypertensive patients.
Several factors have been associated with loss of cognitive function in older adults. According to many studies the educational level is considered to be one of the most important determinants [17
] with less well educated individuals being more likely to have CD. Age has also been linked directly to a loss of cognitive function [61
]. Other factors have also been mentioned in studies such as being female [66
], smoking [67
], atherosclerosis [69
], diabetes mellitus [17
], family history of dementia [73
] and low-income [17
In this study, the atherosclerotic profile, confirmed by increases in LDL cholesterol, triglycerides and subclinical atherosclerosis characterized by increased carotid IMT were associated with higher ORs for cognitive dysfunction in hypertensive patients independently of the pharmacological antihypertensive treatment and the other risk factors for cardiovascular disease.
Elevation of LDL cholesterol levels increase the risk of cognitive dysfunction by 17% in hypertensive patients in agreement with a few previous reports that showed negative effects of the atherosclerotic lipid profile on the cognitive function in adults [30
On the other hand, epidemiological studies in Rotterdam, Netherlands, demonstrated a significant association between various cardiovascular risk factors including hypertension [76
], cerebral white matter lesions and worse performance in neuropsychometric tests [59
]. Additionally, Ikeda et al. [79
], in an analysis of 76 untreated hypertensive patients, 173 treated hypertensive patients and 69 normotensive individuals, showed that the non-treated hypertensive subjects had a higher prevalence of asymptomatic cerebral lacunae at computed tomography compared to normotensive individuals. In this study, the severity and duration of hypertension had a direct correlation with cerebrovascular complications. Studies with large samples showed comparable findings. Liao et al. [79
], for example, studied 1920 subjects using magnetic resonance imaging. Hypertension, smoking and age were associated with a higher prevalence of cerebral white matter lesions although the authors did not investigate possible associations between these lesions and CD. Clinical and epidemiological studies also showed positive results in the analysis of this association. Starr et al. [31
] in a cross-sectional study of 598 elderly, identified a lower mean MMSE score for individuals with high SBP compared to individuals with normal or low SBPs. Prince et al. [32
] performed a case–control study in a clinical trial designed to investigate hypertension treatment in the elderly; a subsample of 50 dementia cases and 223 controls was selected. The study showed that systolic hypertension, without increases in the DBP, was identified as a risk factor for dementia. Launer et al. [80
] identified an 8% increase in the risk of CD for each 10
mmHg increase in SBP among 3,735 Japanese Americans. Freidl et al. [81
], studying a sample of 1927 healthy elderly in the United States, found among the 16 sociodemographic, environmental and behavioral factors investigated that only age and the presence of hypertension were associated with impaired cognitive performance. Our study also showed that age was significantly associated with a decline in the MMSE scores irrespective of BP, biochemical markers and anthropometric variables.
Scuteri et al. demonstrated the role of vascular health in determining cognitive function in older individuals using multiple regression models and showed that arterial stiffness was a strong predictor of loss of cognitive function independent of age, gender, education and traditional cardiovascular risk factors [82
Similarly, vascular remodeling detected by estimating the carotid IMT has been linked to increased risk of cardiovascular, coronary and brain events; this represents an important step in carotid plaque formation and progression and is a characteristic marker of atherosclerosis. [83
]. Of the different pathophysiological explanations, an association between increased IMT and greater pressure variations found in hypertensive patients with vascular remodeling has been described [86
]. On the other hand, Forman et al. reported that endothelial-dependent and endothelial-independent vascular responsiveness was correlated with neurocognitive performance among older cardiovascular disease patients, particularly in respect to the attention-executive domain. [87
With clinical observation, there is a non-consensual understanding that the different forms of hypertension and the results of complications in target organs, related to stiffening of the vascular wall and atherosclerotic plaque formation among other things, are associated to micro- and macro-infarcts of the white substance and is an important causal agent of CD [60
]. However, there are few studies in the literature on the association of vascular structural alterations and CD. The results of the current study demonstrate that structural alterations characterized by increased carotid IMT are significantly associated with hypertension in the hypertensive group with CD when compared to hypertensive patients without CD and the CT group and may provide additional information to conventional risk factors for cognitive dysfunction.
There are also few publications in the literature regarding functional hemodynamic changes in hypertensive patients with CD. Our study shows that hypertensive patients, both with and without CD, have significantly higher CSBP compared to the CT group. However, there was no statistically significant difference in the CSBPs of hypertensive patients with and without CD.
There were no statistically significant differences for the Augmentation Index corrected for HR between the three groups (HCD, HNCD and CT).
Several hypotheses may explain the absence of significant differences between hypertensive patients with and without CD. Antihypertensive therapy using renin-angiotensin-aldosterone blockers and calcium channel blockers interferes in the hemodynamics of arterial, central and peripheral BP thus favoring a reduction in the height of the central pressure wave, thereby reducing the Augmentation Index and the central SBP. However, this does not invalidate the important structural finding represented by the main alteration found in the hypertensive group with CD; vascular remodeling characterized by increased carotid IMT.
Potentially confounding effects of antihypertensive therapy on vascular structural and hemodynamic changes may influence cognitive function. In this study the antihypertensive medication did not influence the results (specifically beta-blockers, ACE inhibitors, ARBs and calcium channel blockers).
This study has some limitations: the results are based on a cross-sectional study and so a longitudinal approach is needed to confirm the influence of age on results. Additionally we cannot exclude the influence of genetic factors on the pathophysiology of CD in hypertensive patients. However, new opportunities for structural and functional hemodynamic evaluations are presented for prospective studies on hypertensive patients who have risk factors for CD which may reinforce the importance of achieving the goal in the treatment of hypercholesterolemia in high-risk patients to prevent CD.