Cardiovascular risk factors and future risk of Alzheimer�s disease
Rene FAG de Bruijn
0
1
3
M Arfan Ikram
0
1
2
3
0
Department of Neurology, Erasmus MC University Medical Center
,
's-Gravendijkwal 230, 3015, CE, Rotterdam
,
the Netherlands
1
Department of Epidemiology, Erasmus MC University Medical Center
,
Wytemaweg 80, 3015, CN, Rotterdam
,
the Netherlands
2
Department of Radiology, Erasmus MC University Medical Center
,
's-Gravendijkwal 230, 3015, CE, Rotterdam
,
the Netherlands
3
Department of Neurology, Erasmus MC University Medical Center
,
's-Gravendijkwal 230, 3015, CE, Rotterdam
,
the Netherlands
Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD.
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Introduction
Alzheimers disease (AD) is the most common subtype
of dementia, and has a large patient and societal burden.
AD has a complex and multifactorial etiology that
involves senile plaques and neurofibrillary tangles [1].
Increasingly, the role of cardiovascular disease (CVD) is
also being recognized as an important etiologic hallmark
of AD. Indeed, many studies have shown the importance
of vascular pathology in AD [2-7]. As CVDs have
established therapeutic options and the risk factors of CVD
are modifiable, focusing on the association between
vascular pathology and AD might provide pathways to
prevent or delay AD in elderly individuals [8,9]. In this
narrative review, we provide an overview of the current
knowledge on the relation between AD and clinical
CVDs, imaging markers of pre-clinical CVD, and
established and emerging cardiovascular risk factors (Table 1).
Review
Cardiovascular disease
CVDs, such as stroke, atrial fibrillation, coronary heart
disease (CHD), and heart failure are very common in
elderly individuals and have regularly been linked to AD.
This association might be due to shared risk factors
between CVDs and AD, but there might also be a direct
causal association as cardiac disease causes
hypoperfusion and microemboli, which have been implicated in
the etiology of AD [10,11]. In the following sections, we
discuss current evidence relating common CVDs with
risk of AD.
Stroke
Clinical stroke has often been associated with an
increased risk of subsequent dementia, but this is by
definition then termed post-stroke dementia or vascular
dementia [12]. Such terminology hampers thorough
investigation of the role of clinical stroke in AD. Therefore,
important evidence implicating stroke in the etiology of
AD comes from studies investigating asymptomatic or
silent stroke, which are often lacunae. Numerous studies
have shown that lacunae strongly increase the risk of
dementia, including AD [13-15]. Moreover, white matter
lesions, which also represent ischemic brain damage, are
also associated with cognitive impairment and AD [16,17].
These findings suggest that stroke is causally involved in
the etiology of dementia. Mechanisms underlying this
association include the following. Firstly, stroke causes loss
of neuronal tissue, which might enhance the degenerative
effect of neuronal tissue loss as a result of amyloid and tau
pathology [15]. Secondly, it has been suggested that
cerebrovascular disease directly influences amyloid pathology
Table 1 List of potential vascular factors implicated in Alzheimers disease
Pre-clinical markers of cardiovascular disease
Established cardiovascular risk factors
Lacunae and white matter lesions
Retinal vascular changes
Microstructural integrity and connectivity
as a result of accelerating amyloid production or
hampering amyloid clearance [3,18], although studies on
these pathways remain inconsistent [3,18-21].
Atrial fibrillation
Several studies have shown that individuals with atrial
fibrillation (AF) more often have AD and are at an
increased risk of AD [22-24]. Because AF causes
embolisms that could lead to stroke, the relation between AF
and AD might be explained by clinical or silent stroke
[10,25-27]. Accordingly, a meta-analysis showed that a
consistent relation between AF and a higher risk of
dementia was restricted to individuals with stroke [23].
However, another study found that stroke-free
individuals with AF performed worse on memory and learning
tasks, and had a reduced hippocampal volume [28]. Both
memory function and hippocampal volume are strongly
related to AD, which suggests there might be additional
pathways explaining the association bet (...truncated)