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The raise of life expectancy has increased the inci­dence and prevalence of age-related diseases. The de­mographic changes of occidental world, characterized by an explosive growth up of population over 65 years, made expected that the problem size will become epide­mic during the first half of this century (Gómez Viera, Ro­dríguez, Gómez, Fernández & González Zaldívar, 2003). The considered disorders include neurodegenerative ones. Among them, dementias have the higher impact on public health due to their high social and economic costs (Butman et al, 2003). The patients, their families and their caregivers must face a significant loss of life quality and a consequent economic burden (Lima Argimon, Quarti Irri­garay & Milnitsky Stein, 2014).

Neurodegenerative disorders do not appear suddenly, but are preceded by early stages of gradual deterioration that usually can go unnoticed for the person and their fa­mily. This process, known as mild cognitive impairment (MCI), it’s characterized by a progressive loss of cognitive functions at a higher lever than the attributable to normal aging (Petersen et. al, 1999). Their early detection is use­ful for family and medical guidance of the future patient, as well as for the planning of compensatory strategies appli­cable to daily life (Albert, 2011; Artero, Petersen, Touchon y Ritchie, 2006). It should be noted that the conservation of practical –implicit- intelligence usually attenuates the impacts of cognitive decline in the everyday life of people who are passing through normal aging (Miranda, Pruvost, Palau, Rimoldi, Viale y Cáceres, 2015).

Hypertension (HT) is a chronic heart disturbance linked to numerous comorbid diseases, with a higher pre­valence in low and mid-income countries. This appears as an obstacle to life quality improvement, worsened by the relative low budget destined to its control and preven­tion (World Bank, 2014). The impact of HT can be verified in several body systems and activities. As consequence, this pathology may be even linked to cognitive and beha­vioral changes (Ovale Jaramillo, Álvarez Diez & Ibañez Pinilla, 2012).

Longitudinal studies on hypertensive patients proved that various cognitive functions impaired more as longer as the hypertensive disorder was conserved (Birkenhä­ger, Forette, Seux, Wang & Staessen, 2001). This corre­lation between hypertensive disease and low neuropsy­chological performance has been verified in samples of middle-aged subjects (Singh-Manoux & Marmot, 2005), like in older adults (Saxby, Harrington, McKeith, Wesnes & Ford, 2003).

Although there are differences in the methods used for the analysis and different hypotheses regarding the causes, there is actually enough evidence to support the relation between hypertensive disorders and cognitive im­pairment.

Thus, it has been shown that hypertension is positi­vely correlated with visual memory decrease (Elias et. al, 1997), increasing global mental deterioration of subjects in their last decades. It has been also verified that hyper­tensive patients get lower yields in complex cognitive functions, such as spatial orientation and calculus; deficits that could also be related with any other of the behavioral expressions of dementia (Arias de Castillo, 2014; Chá­vez-Romero, Núñez-López, Díaz-Vélez y Poma-Ortíz, 2014; Espinoza, Quijada, Chuki y Berbesi, 2017). Accor­dingly, patients with hypertension concomitant diseases have shown a depletion of their attention capacity (Lama & Jeninson, 2013).

Longitudinal studies have analyzed samples with hypertensive subjects in contrast to normotensive sub­jects. These investigations managed to isolate the hyper­tensive factor and to relate it with the differences found in its neuropsychological results (Matoso, Santos, Moreira, Lourenço & Correira, 2013).

Method

A search for articles referred to cognitive performan­ce impact of hypertension was performed utilizing the keywords: hypertenson and cognitive impairment in five scientific databases: Ebsco, Redalyc, Dialnet, Scielo, and Directory Of Open Acces Journals. Based on the infor­mation gathered, a categorization was made to justify the correlation between hypertension and cognitive impair­ment starting with the theoretical explanations with major empirical support. In the present article, the most rele­vant evidences are analyzed in relation to each one of the hypotheses and their concordances and divergences are discussed. Applied inclusion criteria were as follows: abs­tract in English and published in the period 2000-2015. Papers before 2000 were cited only to reference general concepts. Being a theoretical work with exploration tar­gets, the performed screening should not be considered as exhaustive.

Results

Having found enough evidence about the link be­tween hypertensive diseases and the decrease of various cognitive functions, it is necessary to detail the factors that currently intend to justify this relation.

The three postulates that currently have higher em­pirical support and represent the themes addressed by a majority of studies are listed below: 1) cognitive impair­ment as a comorbid disorder with hypertensive diseases; 2) hypertension as a brain damage causal that lead to cognitive impairment, and 3) cognitive impairment as an undesirable effect of antihypertensive medication. It must be noticed that, although each postulates is presented se­parately, literature shows that the association of cognitive performance and hypertension disorders could probably be sustained by a convergence of the three statements. The proposed order in this article responds uniquely to expository reasons.

Hypertension and cognitive decline as related by co­morbidities

Hypertension is a present condition in different disor­ders, so it is reasonable to assume that cognitive impair­ment would be concomitant to broader pathologies. Some of these diseases are the following:

Diabetes type II

Studies concerning diabetes mellitus type II have yiel­ded significant evidence tending to prove the concomi­tance hypothesis. Being a high morbidity disorder, it fa­cilitates accomplishment of detailed longitudinal studies, allowing to assess its impact on cognitive performance. The presence of hyperglycemia seems to be an impor­tant variable, since it has been found a lower cognitive impairment in patients without hyperglycemia (Morris, Vi­doni, Honea, Burns & Alzheimer’s Disease Neuroimaging Initiative, 2014). Current data appears to be conclusive in the consideration of cognitive impairment as one conse­quence of diabetes mellitus type II (Yaffe et. al, 2013).

Dyslipidemias

Dyslipidemia involves a symptomatic scenario that signs presence of metabolic disorders as a common fac­tor. It has been verified the impact that metabolic disor­ders have on some expressions counted as mood states. Recent studies have positively correlated the presence of dyslipidemia related disorders with negative adjustments in cognitive abilities (Bulhões et. al, 2013).

Obesity

Similar consequences have been observed in obe­sity. Although it can be considered a precisely-defined disorder, it appears related with others disorders in diffe­rent systems. Thus, the links between obesity and cog­nitive impairment has shown contradictory results (Beni­to-León, Mitchell, Hernández-Gallego & Bermejo-Pareja, 2013). Although it is possible to indicate that cognitive de­cline may be tied to several obesity-related phenomena and possibly not with the specific obesity phenomenon, it does not result illogical to considerer a more broad conco­mitance between obesity and cognitive impairment (Sellbom & Gustand, 2011).

Heart diseases

Hypertension can be one of direct consequences of heart disease. Thereby, samples of hypertensive subjects usually integrates a considerable number of cardiopa­thic individuals. The vast variability of disturbances, cau­ses, installation time and morbidity rate, caused different appreciations about the impact that might have on cog­nitive performance. However, this relation has extensive evidence to be considered (Eggermont, De Boer, Muller, Jaschke, Camp & Scherder, 2012).

Cerebrovascular disorders

The association between disorders of the cerebral vasculature and cognitive impairment -which will be ex­panded in section Hypertension and cognitive impair­ment of this article- has been extensively studied due high prevalence of dementias secondary to cerebrovascular accidents, with a relatively quick impact of these condi­tions on the patient behavior (Marchant et. al, 2013).

Other pathologies

Deterioration of cognitive ability seems to be related as well with other diseases in several systems. Correla­tions of these deficits with functional shifts on central ner­vous system and reproductive system, such as benign prostatic hypertrophy in hypotensive patients have been confirmed (Park, Rha & Ko, 2013); also, respiratory disea­ses such as asthma seems to have an impact on these symptoms (Caldera-Alvarado, Khan, Delfina, Pieper & Brown, 2013). These linkages have various but incon­clusive empirical evidences. However, we have included them in this review with the purpose of demonstrate the wide range of disorders that involves concomitant hyper­tension and cognitive decline.

Hypertension and cognitive impairment as related to brain damage

Hypertension promotes changes in the arterial sys­tem and cerebral vessels. These changes constitute an adaptive response to excessive pulsatile blood pressures which provokes an anatomical modification leading to atherosclerosis, arteriolesclerosis, arterial wall thickening, narrowing arterial diameter, and smooth muscle hyper­trophy. The lack of blood flow in brain key areas leads to neural performance decrease, and to corresponding efficiency decline on various cognitive functions whose might cause executive dysfunction. There is also enough evidence to indicate that blood pressure disorders can be considered as prognostic predictors of cognitive dysfunc­tions for elderly patients (Paulson, Strandgaard & Edvins­son, 1989).

One of the possible derivations of hypertension is the thickening of vessel walls, which tends to cause cerebral microangiopathy. Those disorders have been positively correlated with low efficiency in global cognitive perfor­mance assessments, and with memory especially when the damage is located in the frontoparietal lobe (Quinque et. al, 2012).

Insufficient blood supply is also often caused by hypertension-related accidents, such as brain microin­farcts and multiple strokes. These episodes might lead to vascular dementia, the second most prevalent dementia type in older adults (Zhang et. al, 2012), with typical me­mory dysfunction symptoms, and decrease of at least two higher cognitive functions (Davies, Ben-Shlomo & Martin, 2011).

Adaptive degenerative changes observed as result of HT on circulatory system provokes, as overall impact, cortical atrophy. Cognitive impact of this disease tends to worsen as anatomo-physiological effects are accentua­ted. Naturally, the dementia location focus and etiology are usually related to specific types of cognitive effects. Longitudinal studies describes the dementia progress as a gradual ability loss to daily task perform, plus a gra­dual impoverishment in neurocognitive performance tests (Chan et. al, 2015).

Although magnetic resonance studies can determine the focus and areas affected by cerebral microcirculation disorders, it’s still difficult to predict the cognitive effects of neural injuries, since technologies needed to determi­ne small vascular damages are not completely developed with required efficiency.

Hypertension and cognitive impairment associated by medication side effects

Antihypertensive drugs can be categorized based on its action mechanisms used to modify the blood pressure, as follows: beta blockers, angiotensin enzyme converting inhibitors, angiotensin receptor blockers, and calcium an­tagonists. Although numerous drugs apply more than one active principle, it remains useful to analyze the influence of each one of these groups in cognitive performance.

Beta blockers works reducing myocardial rhythm and potency, resulting in: a decrease of blood volume and flow rate; inhibition of rennin production; stimulation of kinins production; and the generation of a central antisympathe­tic effect. Cognitive impacts of those drugs might vary in relation to each specific chemical compounds ones, but in general are positively correlated with a decrease in me­mory performance (Fogari et. al, 2003).

Instead, angiotensin converting enzyme inhibitors produces a renin decrease by declining its precursor, the angiotensin. It produces relaxation of blood vessels by in­creasing its luminal space. It seems that its administration finds positive linkages with cortical shifts, which integra­te similar features to various memory disorders markers (Savaskan et. al, 2001).

Likewise, the called angiotensin receptor blockers, in­hibits the angiotensin cellular receptors, reducing its per­formance on renin production. Some scientific literature denominates those drugs as angiotensin blockers type II. It was found that several drugs of this type could be res­ponsible for neuropathologies (Hajjar, I., Brown, L., Mack, W. J., & Chui, H., 2012).

Also, calcium antagonists inhibit calcium entrance into cells, reducing the narrowing tendency of small ar­teries. This allows to reduce myocardial contractility and peripheral vascular resistance. It seems that its supplying could acts as source of shifts in memory functions (John­son, Ait-Daoud & Wells, 2000).

Diuretic drugs produce sodium elimination through nephro-urologyc system, which reduces the circulatory flow volume. Data concerning its cognitive impact is stri­king, since some studies found a positive relation between the administration of these drugs and an increase in lear­ning tasks performance. Nor does it appears to cause negative effects on memory performance (Yasar et. al, 2012). Despite these evidences, it is necessary to say that diuretics drugs are not antihypertensive drugs themsel­ves, but are supplied in early stages of this disorder due to its contribution to some symptomatic attenuation.

While chronic medication can be necessary for a number hypertensive disorders wich could otherwise re­sult in serious drawbacks, it is important to consider its potential impact on brain functioning. Drug treatment is usually sustained for several decades, which would maxi­mize the possibility of a cognitive decline.

Conclusions

The expose of the three theoretical explanations gi­ven in this article seems to show that correlation between hypertension and cognitive impairment could be a mul­ti-causal phenomenon, and that each scenario should be considered without excluding the others.

It is expected that technological advances on neu­rologic diagnoses techniques will allow to elucidate with greater accuracy the causal relations behind the scena­rios that currently can only be expressed on correlative means. We wish to emphasize the consideration given to the advantages and disadvantages of chronic antihyper­tensive medication, due the proven negative impact which most of this drugs cause on cognition. In this same theme, there is a critical disproportion among the available scien­tific data related to functions such as memory and atten­tion, to detriment of the data over higher processes such as executive functions. Finally, we appeal to a techniques homogenization for diagnosis and monitoring of disorders related to cognitive impairment.

Discussion

Given the gathered information, it seems reasonable to hold the existence of a significant association between hypertension and cognitive impairment. However, it is ne­cessary to evaluate new interpretations of existing data, and to encourage further researches to clarify the link.

We located vast evidence about changes in memory functions, but we could not find the same amount of scien­tific production in reference to higher cognitive abilities, such as executive functions. Would be reasonable to ask if the environment-related adaptive sensitivity of executi­ve functions results in a protective trait or, conversely, in a vulnerability trait regarding the effects of hypertension.

In this meaning, we emphasize the relevance of in­terdisciplinary dialogue and integral training of professio­nals. In scenarios where the factor convergence can be considered as an overlap, the organic approach of one disorder should not deprive the consideration of its neu­ropsychological derivations. Being HT as common as broad in consequences, is convenient to consider the full impact spectrum of its treatment on the patient daily life.

We believe that diagnostic techniques advances will allow a more detailed observation of the small-sca­le effects of hypertension over specific brain structures. Meanwhile, we insist on the need of accurately warn about benefits and harms of chronic use of antihyper­tensive medication. Likewise, it corresponds to privilege the consensus generation of criteria and methodology. Otherwise, heterogeneity of data, classifications and tests, may limit the concrete application of any progress accomplished in the researches. Hypertensive disorders and cognitive impairment are diseases typically associa­ted to the age span of which we expect a major growth in coming decades. Therefore, addressing these issues has a pronounced preventive and epidemiological importance for health containment. Under current demographic data, strategies aimed to reduce health care cost, and to im­prove protection and integration of these age groups will represent targets and urgencies with growing importance.

Considering that pharmacological strategies have been found ineffective over mild cognitive impairment, we reinforce the early detection importance, as well as preventive or palliative approaches which include: perio­dic cognitive assessment, clinical and psychological fo­llow-up, stimulation activities that reinforce the conserved neuroplastic capacity, and guidance for family and caregi­vers. By this way, it is possible to expect concrete impro­vements of life quality for patients and their families.

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