**1. Introduction**

The aging of the population is a worldwide phenomenon, and studying age-related diseases has become a relevant issue from both a scientific and a public health perspective. Dementia is a syndrome characterised by loss of cognitive abilities in multiple domains that results in impairment in normal activities of daily living and loss of independence [1]. Both prevalence and incidence of dementia rise exponentially with advancing age, and 70% of all dementia cases occur in people aged 75+ years [2]. The worldwide increase in the number of older adults, more pronounced in the 80+ age group, explains the epidemic proportions assumed by dementia. According to the World Alzheimer Report, there were 35.6 million people living with dementia worldwide in 2010, a number that will increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means reducing the disease incidence are introduced [3]. Dementia is a major cause of disability and institutionalization of elderly people and because of its increased prevalence this disorder is becoming an emerging public health issue not only in developed countries but also in less developed regions of the world. The total estimated worldwide costs of dementia were US\$604 billion in 2010, including the costs of informal care (unpaid care provided by family and others), direct costs of social care (provided by com‐ munity care professionals, and in residential home settings) and the direct costs of medical care (the costs of treating dementia and other conditions in primary and secondary care) [3].

Alzheimer's disease (AD) is considered the most common cause of dementia, accounting for 60–70% of all dementia cases. The hallmarks of AD neuropathology in the brain are the presence of extracellular plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated aggregates of the microtubule-associated tau protein [4].

© 2013 Mangialasche et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Vascular dementia (VaD), mainly due to cerebrovascular diseases (CVD), is the second most frequent type of dementia [5, 6]. This current classification of dementia types is being recon‐ sidered in light of recent neuropathological and neuroimaging studies, which have shown a range of dementia-associated brain abnormalities from pure vascular lesions at one end to pure AD pathologies at the other, with most dementia cases being attributable to both CVD and AD. In fact, AD and CVD-related changes often coexist in the brain of older adults with dementia and mild cognitive impairment (MCI) [7, 8]. Also, both types of lesions are detected in the brain of cognitively normal elderly people, highlighting the importance of mixed pathologies in increasing the risk of late-life dementia [9]. The co-occurrence of AD and CVD is consistent with the evidence that AD and VaD share several risk and protective factors, including cardiovascular and lifestyle related factors. Overall, this implies that dementia syndrome is a valid target for prevention, especially from the public health perspective.

secondary prevention in order to halt the progression of the brain damage and prevent or delay the onset of cognitive symptoms. A step in this direction has been done by planning random‐ ized controlled trials (RCTs) testing anti-amyloid drugs in older adults with evidence of brain amyloid accumulation. The same type of intervention will also be tested in subjects at risk of

Prevention of Alzheimer's Disease: Intervention Studies

http://dx.doi.org/10.5772/55034

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This chapter summarizes the major findings concerning primary prevention of late onset dementia and AD, based on current epidemiological evidence from observational and interventional studies. Preventive strategies for early onset AD are also mentioned. Although many aspects of the dementias are still unclear, some risk and protective factors have been identified. It is also possible to delineate some preventative strategies. Ongoing interventional studies testing the effect of preventive measures for dementia and AD are discussed, and

Several community-based prospective studies of aging and health have been carried out in different countries since the 80s'. These studies have provided relevant information on the aetiology of dementia and AD, and have led to the identification of possible preventive strategies. Evidence from these observational studies has shown that dementia is a multifac‐ torial disorder caused by several interrelated mechanisms in which the interaction of genetic and environmental factors plays the major role (Table 1). The pathways that lead from different risk factors to dementia are not fully understood, but several etiological hypotheses have been proposed: the vascular hypothesis, inflammatory hypothesis, oxidative-stress hypothesis, toxic hypothesis and psychosocial hypothesis [18, 19]. These theories highlight potential links of various risk factors to both the vascular and the neurodegenerative brain pathologies that can cause dementia, supporting the validity of dementia syndrome as target for prevention [6,

Both modifiable and non-modifiable risk factors have been identified for dementia and AD, and while for some factors the scientific evidence is quite robust, for others the results are still

Increasing age is a well-established risk factor for dementia, which is a common disorders after 75 years of age, but rare before age 60. The incidence rates of dementia increase exponentially with advancing age. In Europe, approximately two per 1,000 person-years become demented among people aged 65-69 years, and the incidence increases to 70 to 80 per 1,000 person-years for people 90 years or over [21, 22]. It is still unclear if the incidence of dementia continues to increase even in the oldest old or reaches a plateau at a certain age. The Cache County Study found that the incidence of dementia increased with age, peaked, and then started to decline

methodological challenges in designing dementia prevention trials are summarized.

early onset AD due to genetic mutations associated with familial AD.

**2.1. Non-modifiable risk factors for Alzheimer's disease**

**2. Observational studies**

20].

inconclusive.

*2.1.1. Age*

Prevention is traditionally divided into three levels: primary, secondary, and tertiary preven‐ tion. Primary prevention aims to reduce the incidence of the disease by eliminating or treating specific risk factors, which may decrease or delay the development of dementia. Secondary prevention aims to early detection of the disease, before any symptom has emerged, when treatment could stop its progression. Tertiary prevention aims to reduce the impact of complications and disability of long-term diseases.

Regarding primary prevention, both observational and interventional epidemiological studies have been conducted for dementia and AD. On the other hand, in the field of AD the devel‐ opment of pharmacological interventions has been mainly limited to a tertiary prevention level, since the diagnostic criteria currently in use for AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, NINCDS-ADRDA - criteria) identify the presence of the disease only when AD is severe enough to cause a dementia syndrome [10]. Thus, the majority of anti-AD drugs have been tested in subjects already in the symptomatic stage of the disease, and so far no drug has shown the ability to stop the disease progression (i.e. disease-modifying effect) [11]. However, several studies have shown that the pathophysiological process of AD begins years, if not decades, before the diagnosis of Alzheimer's dementia and individuals generally experience a gradual impairment of cognitive functions, which can progress to a dementia syndrome [12-14].

Recent advances in neuroimaging, cerebrospinal fluid (CSF) assays, and other techniques now provide the ability to detect evidence of the AD pathophysiological process in vivo, but the diagnostic criteria currently in use do not take into account these biomarkers. Three interna‐ tional workgroups promoted by the American National Institute of Aging (NIA) and the American Alzheimer's Association recently proposed new diagnostic guidelines to identify dementia due to AD, MCI due to AD, and preclinical AD [15-17]. These new criteria formalize the different clinical stages of AD and incorporate biomarkers (genetic, biochemical, neuroi‐ maging) that can be detected in vivo and are believed to reflect AD pathology. These diagnostic criteria are now being validated and can be revised as long as new findings from research on biomarkers in AD will clarify the link between AD pathophysiology and the AD clinical syndrome. These criteria offer the opportunity to identify subjects who can be target of secondary prevention in order to halt the progression of the brain damage and prevent or delay the onset of cognitive symptoms. A step in this direction has been done by planning random‐ ized controlled trials (RCTs) testing anti-amyloid drugs in older adults with evidence of brain amyloid accumulation. The same type of intervention will also be tested in subjects at risk of early onset AD due to genetic mutations associated with familial AD.

This chapter summarizes the major findings concerning primary prevention of late onset dementia and AD, based on current epidemiological evidence from observational and interventional studies. Preventive strategies for early onset AD are also mentioned. Although many aspects of the dementias are still unclear, some risk and protective factors have been identified. It is also possible to delineate some preventative strategies. Ongoing interventional studies testing the effect of preventive measures for dementia and AD are discussed, and methodological challenges in designing dementia prevention trials are summarized.
