Cardiovascular risk factors and future risk of Alzheimer�s disease

BMC Medicine, Nov 2014

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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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. - 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)


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Ren�e de Bruijn, M Ikram. Cardiovascular risk factors and future risk of Alzheimer�s disease, BMC Medicine, 2014, pp. 130, 12, DOI: 10.1186/s12916-014-0130-5