ABSTRACT

Hypertension is a highly prevalent condition established as a cardiovascular and cerebrovascular

disease risk factor, along with dementia, it is recognized as a common disorder in elderly people.
While understanding of the relationship between cardiovascular dysfunction and brain health has
significantly improved over the past several decades, it remains unclear whether hypertension is a
potential risk factor for cognitive regression and dementia. HT in the elderly is associated with higher
dementia rates, including Alzheimer's disease (AD) and vascular dementia (VaD). Some studies have
suggested in connection with this that HT in old age correlates with dementia pathogenesis.
Although, it is clear that hypertension can affect the structure and function of the brain, recent
findings suggest that the associations between blood pressure and brain health are complex and, in
many cases, depend on factors such as age, chronic hypertension, and use of antihypertensive drugs.
While large epidemiological studies showed a consistent association between high BP in middle aged
and increased incidence of late onset cognitive regression and dementia (middle aged class with high
blood pressure are more likely to present with dementia later in life), associations between late
onset high blood pressure and cognition were less consistent. Recent evidence indicates that high
blood pressure can encourage brain morphologic and physiologic alterations through remodeling of
the cerebral vessel, leading to cerebral autoregulation, reduction of brain infusion, and limiting the
ability of the brain to clear potentially harmful proteins such as β-amyloid. This review aims at
synthesizing the latest findings in an overview of the current knowledge regarding the relationship
between blood pressure and cognitive function throughout our life cycle from epidemiological,
neuro-imaging, physiological, genetic and translational research.

INTRODUCTION

Hypertension is highly prevalent in 1/3 of adults worldwide and 2/3 of adults over sixty-five years of
age (Kearney et al., 2005). Evidence that hypertension can also play a significant role in the
development of cognitive decrease, Alzheimer's disease and vascular dementia (Kennelly SP, Lawlor
BA, Kenny RA, 2009) has already been established for cardiovascular and cerebrovascular disease
(MacMahon et al., 1990). Because hypertension is a modifiable risk factor, it is a crucial mechanism
through which it is possible to prevent or delay age-related cognitive disorders. Therefore, the
research priority in the last two decades has been to understand the role of hypertension in the
development and progression of age-related cognitive impairment and dementia. Although much
was learned from epidemiology, the effectiveness of hypertension therapy in preventing or slowing
cognitive decline remains unknown. What is evident, however, is the biologically complex and still
not fully understood connection between blood pressure (BP) and cognitive function.

The objective of this review is to analyze studies which has helped to understand the relationship
between BP and cognitive function, with careful attention paid to recent results. This review
provides an overview of the known links between hypertension, cognitive function, Alzheimer's
disease and vascular dementia. Secondly, it will describe neurobiological alterations associated with
hypertension and will show how these biological processes affect neuronal function. Finally, the
results of clinical studies aimed at assessing the effectiveness of antihypertensive drugs for cognitive
decline prevention or delay will be summed up. Methodological and specific recommendations will
also be discussed for future research. Although this review focuses on the subject of hypertension
and cognitive function, it also discusses the link between low BP and cognition.
HYPERTENSION AND COGNITIVE FUNCTION

During the past few decades, many age groups have been examining the link between hypertension
and cognitive function. Much of these studies focused on understanding the relationship between
BP and cognition in the elderly, the group most likely to experience cognitive impairment, but
studies that evaluate BP from the middle ages have also been informative and follow up participants
until they reach old ages. Many epidemiological studies have shown that higher BP, especially
untreated hypertension, within the 4th and 5th decade of life, increases the risk of cognitive
impairment 20-30 years later (Launer et al., 1995). These findings were further endorsed by
longitudinal studies that indicated that high BP in middle aged class was associated with increased
cognitive impairment over the long term (Gottesman et al., 2014). Because confounding variables
such as education and socio-economic status (as compared to baseline cognitive abilities) are less
likely to affect cognitive change (Schneider et al., 2012), studies that show an increased cognitive
decrease in hypertensive adults over time have shown particularly strong evidence of high BP
deleterious effects. These studies also identify the course of hypertension and trajectory of BP levels
as key indicators of cognitive function later in life (Power et al., 2013).

Hypertension was associated with poorer cognitive overall function and a reduction in cognitive
function in the 6th and 7th decade (Kuo et al., 2004). The risk factors for mild cognitive impairment
(MCI), the subtle decline in cognition believed to precede the onset of dementia (Cherbuin et al.,
2009), were also found to be hypertension among individuals in their' 70s. In contrast, studies
including individuals in their eighth, ninth and tenth decades have been largely unsuccessful in
finding such correlation (Pandav et al., 2003), or have found that high BP protects against cognitive
impairment (Waldstein et al., 2005). These results together, indicate that in late onset,
the connection between cognition and BP may depend on age (Shang et al., 2016).

Although people who develop hypertension in the early stages of life are likely to be exposed to the
detrimental neurological effects of hypertension till late in life, this is not the case for those who
develop hypertension much later. The strong links between hypertension in midlife and late-
life cognitive skills supports the idea that adult hypertension and chronicity may be particularly
important drivers of cognitive impairment in elderly people. Maybe the greatest support for this
inferential is a longitudinal study which found that a longer period between the onset of
hypertension and cognitive testing is associated with reduced cognitive abilities independent of age
(Power et al., 2013). Longitudinal studies in particular, have suggested that adults of the middle-
aged class with prolonged hypertension and elevated systolic blood pressure (SBP) for 25–30 years
have an exceptionally high risk of cognitive impairment later in their lives (Power et al., 2013). Thus,
research studies with a longer period between BP monitoring initiations and subsequent cognitive
evaluations can better detect neurocognitive outcomes with the impact of high BP. It is also
important to track changes in blood pressure from a medium to older age, since late-life
hypertension and low diastotic (DBP) are linked to reduced brain volumes and less cognitive
outcomes for older adults (Muller et al., 2014). Individuals developing high blood pressure before
the middle of age can also be at particularly high risk for cognitive impairment, as several studies
have shown associations between high PB, cognitive failure and decreased educational performance
in children, adolescents and young adults (Suhr, Stewart, France, 2004). Regardless of age, executive
functioning and information processing speeds are cognitive areas that appear most vulnerable to
hypertension. The integrity of the frontal and subcortical brain structures that are most vulnerable
to the effects of hypertension is a key element in both cognitive processes.
DEMENTIA RISK AND HYPERTENSION

Alzheimer’s disease

Different forms of cardiovascular disease have been identified, which together account for most
dementia cases worldwide (Prince et al., 2013), as risk factors for both Alzheimer's disease and
vascular dementia (Li, Wang, Xiao, 2016). The genetic contributions of Alzhemer's disease, stroke
and cardiovascular disease are shared (Traylor et al., 2016), and about 50% of those diagnosed with
Alzheimer's disease have significant autopsy cerebral pathologies (Schneider et al., 2007). Together,
these findings suggest that the pathophysiology of cardiovascular disease, Alzheimer's disease, and
vascular dementia overlap (Iadecola, 2016). Although there is significant evidence that
cardiovascular disease is involved in pathogenesis and the progression of Alzheimer's disease, it is
still not fully understandable that hypertension is associated with Alzheimer's disease. While there
has been evidence of a consistent relationship between high DBP at midlife and Alzheimer's disease
(Shah et al., 2012), evidence of an association with mid-life SBP has been contradictory (Power et al.,
2011). Late-life hypertension does not seem to be a risk factor for Alzheimer's disease incidence
(Power et al., 2011). In fact, several studies have indicated that an abnormally low DBP can increase
the risk of Alzheimer's disease in late life (Nilsson et al., 2007). Along with the late-life risk of DBP
and the disease of Alzheimer, some, however, did argue that BP tends to simultaneously decline
when the dementia begins and progresses (Li et al., 2007). Concerning the combination of high BP in
midlife and low BP in late life, individuals can be particularly at risk of developing Alzheimer's disease
together, according to previous findings. Few studies have however directly examined this
hypothesis (Glodzik et al., 2014).

Vascular Dementia

Because hypertension is a known risk factor for stroke (Knopman et al., 2011) and diseases of small
vessels of the brain (Raz et al., 2007), hypertension is often considered a risk factor for vascular
dementia, a type of neurodegeneration resulting from cerebrovascular disease of small or large
vessels (Ying et al., 2016). However, only a few studies have analyzed hypertension and vascular
dementia directly. Although earlier research has supported the relationship between midlife
hypertension and the development of VaD, it is unclear whether there is a link between late-life
hypertension and VD, as the results have been contradictory so far. The associations between
midlife hypertension and the Alzheimer's incident tend to be more robust and consistent when
comparing hypertension with vascular dementia. However, this distinction may not mean that the
patients are more likely than pure forms to develop mixed Alzheimer's and vascular dementia.

CONCLUSION

Hypertension can obviously affect the structure and function of the brain, which increases one's risk
of cognitive decline and dementia. The late cognitive deterioration and incident dementia have most
consistently been linked to hypertension, high SBS and high DBP during midlife. Hypertension,
however, was also linked to cognitive deficits of early life and medium life. While the association
among octogenarians and nonagenarians between late-life hypertension and cognitive function is
less obvious, there is little evidence that mildly higher BP in late-life protection against cognitive
degradation, in particular for persons with longstanding hypertension records. Hypertension
duration may be a particularly important determinant of cognitive decline since evidence indicates
that hypertension may have cumulative neurological effects. Few study studies have longitudinally
assessed BP and even fewer have tried to determine retrospectively how long hypertension lives
relate to cognitive function. Due to the increased hypertension prevalence among young people
(McNiece et a., 2007), it will be particularly important to evaluate the cumulative impact of elevated
BP on the entire lifetime to understand how BP can influence neurodevelopment and
neurodegeneration (Lande, Kupferman, 2015).

Recent progress on neuroimaging as well as physiological and hemodynamic surveillance has helped
to better understand the mechanisms that hypertension affects neurocognitive function. The risk
factor for cerebral atrophy, micro-structural harm in white material, and small vessel cerebral
diseases was identified as hypertension, especially in midlife. Evidence shows that hypertension
contributes by promoting vessel wall remodeling and endothelial dysfunction, which leads to
autoregulatory deficits, towards development and growth of such neurological changes. These
changes to the neurovascular unit vulnerable the brain to hypoperfusion caused by systemic BP
drops. Even though it is known how these pathophysiologic processes influence cognitive function
and promote Alzheimer's and vascular dementia in humans, there is much to support this model of
hypertension-induced cerebrovascular changes.
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