Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complaints of memory loss☆,☆☆
Introduction
Advancing age is also characterized by progressive cognitive decline and increased risk for dementia that significantly impacts on loss of personal independency [1]. The prevalence of dementia increases with advancing age, affecting around 7% of subjects over 65 years and 30% of those over 80 [2]. Since there is no effective therapy for dementia, any strategy capable of preventing, delaying its onset and decreasing the rate of progression of the disease will have a great impact on patients and on public healthcare costs. Identification of subjects at faster decline of cognitive function and of factors influencing the trajectory of cognitive decline represents an emerging strategy to reduce the burden of dementia.
In the clinical practice, it is very common that older subjects seek medical attention because of subjective complaints of memory loss. This stage has an unclear prognosis, but increasing evidence suggests that it often represents a preclinical stage of dementia. In fact, older subjects with subjective complaints of memory loss present a 4.5 fold higher risk of developing dementia [3].
In the last years, epidemiological studies provided evidence that vascular contributions to cognitive impairment and dementia are important (see [4] for review). These cardiovascular (CV) and hemodynamic factors have mostly been intended as “local” factors, i.e. related to cerebral district circulation, whereas less attention has been given to systemic hemodynamic factors contributing to cognitive dysfunction in older subjects [5], [6].
Arterial stiffness, measured as Pulse Wave Velocity (PWV), has emerged as a significant risk factor for cognitive decline [7], [8], [9]. Cerebral White Matter Lesions (WML), that can be identified by neuroimaging and are associated with declining memory and executive functions [10], may reflect microvascular brain damage [5] and are both a risk factor for and a consequence of repeated episodes of cerebral hypoperfusion [11]. A stiffer arterial system is accompanied by impaired cerebral autoregulation. Thus hypotensive episodes occurring in the context of a stiffer arterial system may potentiate the risk of brain hypoperfusion and, consequently, of cognitive dysfunction [12].
To render the picture of brain/cognitive function and CV system cross-talk more complex, it should be remarked that many of these arterial, cardiac, hemodynamic, and neuroimaging markers individually reported to be associated with cognitive dysfunction are inter-related. For instance, not only aorta stiffness [8], [9], but also blood pressure (BP) variability [13], [14], increased left ventricular mass (LVMI) [15] or diastolic dysfunction [16] have been associated with poorer cognitive function in older subjects. Aorta stiffness is linked to BP levels and profile over the daily 24 h [17], [18], both aorta stiffness [19] and BP variability [20] are associated with greater LVMI. All these parameters are risk factors for brain White Matter Lesions (WML) [21], [22].
The goal of the present study was to identify baseline predictors of cognitive change in older patients with subjective complaints of memory loss, and more specifically to evaluate the contribution of cardiac, vascular, and hemodynamic factors to cognitive function, independently of each other and of traditional CV risk factors (office blood pressure, plasma lipids, glucose levels and diabetes). Additionally, we tested the possible synergistic effect of the simultaneous occurrence of systemic and cerebral vascular determinants of cognitive impairment.
Section snippets
Study population
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Cross sectional analysis
The study population consisted of patients who visited our center in Rome because of subjective complaints of memory loss in the previous year. Subjects were excluded if they had cancer, acute myocardial infarction in the previous 6 months, hepatic or cardiac failure, serum creatinine > 2 mg/dl, secondary hypertension, or thyroid disease. Additional exclusion criteria were: previous large vessel stroke; atrial fibrillation, since its presence interferes with the accuracy of
Results
Table 1 summarizes the characteristic of the study population. Studied older subjects with subjective complain of memory loss (mean age 78.3 ± 6.3 years) were mostly subjects at high CV risk (78.6% presented hypertension, 22.1% diabetes mellitus, average LDL cholesterol levels were > 130 mg/dl, 83.9% had LVH).
Discussion
The present study conducted in older patients with subjective complaints of memory loss (thus at higher risk of cognitive decline until development of clinical overt dementia) showed that specific systemic hemodynamic and vascular parameters (namely, PWV and episodes of systolic hypotension) together with markers of cerebral microvascular damage (WML) are significant risk factors for age-related cognitive dysfunction and for its progression until cognitive impairment—independently of education,
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Each author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
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The present study was not supported by any specific grant.