More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer’s disease. In both developed and developing nations, Alzheimer’s disease (AD) has had a tremendous impact on the affected individuals, caregivers, and society. The etiological factors of AD, other than older age and genetic susceptibility, remain to be determined. Nevertheless, increasing evidence strongly points to  the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity) in the pathogenetic process and clinical manifestation of the dementing disorders [1]. The long-term multifaceted interventions toward the control of vascular risk factors and the maintenance of socially integrated lifestyles and mentally stimulating activities are expected to reduce the risk or postpone the clinical onset of dementia, including Alzheimer’s disease.

At the individual level, AD significantly shortens life expectancy and is one of the principal causes of physical disability, institutionalization, and decreased quality of life among the elderly. First, AD is strongly associated with functional disability and institutionalization. It is estimated that among individuals over 60 years of age dementia contributes 11.2 % of the years lived with disability, compared with 9.5 % for stroke, 8.9 % for musculoskeletal disorders, and 5.0 % for cardiovascular disease [1]. Follow-up studies of peopleaged 75+ years in Sweden have shown that approximately half of the elderly people who develop functional dependence over a 3-year period can be attributable to dementia and AD [2]. Furthermore, in many industrialized countries, dementia is the most common disease among older adults living in nursing homes or in institutions. Second, epidemiologic studies have confirmed the malignant nature of AD that could confer an excess risk of death for older people, to a similar extent to that of malignant tumors [2]. Several community-based follow-up studies of incident cases showed that AD was associated with a two to five-fold increased risk of death [2,3]. Overall, the median survival time for people with newly diagnosed AD ranges from 3 to 6 years [3].  Factors such as older age, being white and/or of male sex low education, comorbidities (eg, hypertension, diabetes, and heart disease), poorer cognitive function, and physical disability are frequently reported to predict a shorter survival in persons with AD [1].

Not only have dementia and AD diagnoses proven to be both frequent and fatal, yet we are seeing a rapid increase in the number of patients with dementia and AD that will result in tremendous consequences for our society and economy. The number of persons with AD in the US population in 2000 was estimated to be 4.5 million, and by 2050 this number was projected to increase by almost threefold, to 13.2 million [4]! A more recent study indicated that in 2006 the worldwide total number of patients with AD was 26.6 million, and by 2050 the number will quadruple [4].Additionally, it is estimated that about 43 % of AD patients require a high level of care such as nursing homes and institutions. As diagnoses continue to increase,Long-term institutional care will be the main cost in many developed countries, whereas in developing countries informal home care provided by family members is usually the only source available for patients with dementia [5]. Even in the US, almost 10 million Americans (eg, family members, friends, and neighbors) provided unpaid care for persons with AD or other dementia [4,5] Thus, enormous resources will be needed for adequate care of Alzheimer and dementia patients. The worldwide, overall societal costs of dementia were estimated to be more than US$315 billion in 2005, including one third for informal care;35 approximately three fourths of the global costs for dementia occurred in middle income countries where about 46% of dementia patients reside [5]. The 2009 reports from Alzheimer’s Association showed that in the US,  the annual costs for patients with AD and other dementia were estimated to be US $148 billion plus US $94 billion unpaid care service, and that AD tripled health care costs for Americans aged 65+ years [6]. It is anticipated that modest advances in therapeutic and preventive strategies that lead to even a 1-year delay in the onset and progression of clinical AD, will significantly reduce the global burden of this disease; however, given the contemporary burden of dementia and AD, analyzing risk factors is more important than ever. [5].

Alzheimer’s dementia is a multifactorial disease, in which older age is the strongest risk factor, suggesting that the aging-related biological processes may be implicated in the pathogenesis of the disease. Furthermore, the strong association of AD with increasing age may partially reflect the cumulative effect of different risk and protective factors over the lifespan, including the effect of complex interactions of genetic susceptibility, psychosocial factors, biological factors, and environmental exposures experienced over the lifespan [7]. 

A systematic review found that psychosocial factors and actively integrated lifestyle over the lifespan may reduce the risk of AD and dementia. [7]. These factors include early-life high educational attainment, adult-life high work complexity, late-life rich social network and high levels of social engagement, and more frequently participating in physically and mentally stimulating activity [7].

An association of low education with an increased risk of dementia and AD has been reported in numerous cross-sectional and longitudinal studies. Education and socioeconomic status are highly correlated; however, when both measures were examined simultaneously, the independent association was detected only with education [8]. The reserve hypothesis has been proposed to interpret this association such that education could enhance neural and cognitive reserve that may provide compensatory mechanisms to cope with degenerative pathological changes in the brain, and therefore delay onset of dementia syndrome [8]. Alternatively, educational achievement may be a surrogate or an indicator of intelligence quotient, early life living environments, and occupational toxic exposure experienced over adulthood [9].

Evidence from longitudinal observational studies suggests that a poor social network or social disengagement is associated with cognitive decline and dementia [10]. The risk for dementia and AD was also increased in older people with increasing social isolation and less frequent and unsatisfactory contacts with relatives and friends. Furthermore, a recent study suggested that low neuroticism (long-term tendency to be in a negative or anxious state) in combination with high extraversion (finding gratification outside oneself, primarily with positive human interaction and socialization) was the personality trait associated with the lowest dementia risk, and among socially isolated individuals even low neuroticism alone seemed to decrease the risk of dementia  [11]. Finally, low social engagement in late life and a decline in social engagement from middle age to late life were associated with a doubly increased risk of developing dementia and AD in late life [10]. Rich social networks and high social engagement imply better social support, leading to better access to resources and material goods. Rich and large social networks also provide affective and intellectual stimulation that could influence cognitive function and different health outcomes through behavioral, psychological, and physiological pathways [12].

Regular physical exercise was also reported to be associated with a delay in onset of dementia and AD among cognitively healthy elderly [13]. In the Kungsholmen Project, the component of physical activity present in various leisure activities, rather than sports and any specific physical exercise, was related to a decreased dementia risk [13]. In addition, low-intensity activity, such as walking, may reduce the risk of dementia and cognitive decline. A strong protective effect of regular physical activity in middle age against the development of dementia and AD in late life was reported, especially for persons with the APOE ε4 allele [14]. As it may take years to achieve high levels of physical fitness, brief periods of exercise training may not have substantial benefits on cognitive processes, but could still be detectable in the subsets of cognitive domains that are more sensitive to the age-related decrements. Physical activity is important not only in promoting general and vascular health, but also in promoting brain plasticity, and it may also affect several gene transcripts and neurotrophic factors that are relevant for the maintenance of cognitive functions [13].

Various types of mentally demanding activities have been examined in relation to dementia and AD, including knitting, gardening, dancing, playing board games and musical instruments, reading, social and cultural activities, and watching specific television programs, which often showed a protective effect [15]. Due to the cultural and individual differences in choosing specific activities, some researchers summarize mentally stimulating activities into a composite, score, which showed that a cognitive activity score involving participation in seven common activities with information processing as a central component was associated with a reduced risk of AD, even after controlling for APOE ε4 allele, medical conditions, and depressive symptoms [16]. The Swedish Twin Studyshowed that greater complexity of work, and particularly complex work with people, may reduce the risk of AD [17]. The Canadian Study of Health and Aging found that high complexity of work appeared to be associated with a reduced risk of dementia, but mostly for vascular dementia [18].  In support of these findings, the recent neuroimaging study suggested that a high level of complex mental activity across the lifespan was correlated with a reduced rate of hippocampal atrophy [18].

Alzheimer’s disease represents an increasing challenge to public health and the health care system and has had tremendous impact at both the individual and the societal levels. Epidemiologic research has provided sufficient evidence that vascular risk factors in middle-aged and older adults play a significant role in the development and progression of dementia and AD, whereas extensive social network and active engagement in mental, social, and physical activities may postpone the onset of the dementing disorder. Multidomain community intervention trials are warranted to determine to what extent preventive strategies toward optimal control of multiple vascular factors and disorders, as well as the maintenance of an active lifestyle, are effective against dementia and AD.


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