**2. Socio-behavioral proxies in the prevention of cognitive decline and dementia**

One of the major limitations of the CR construct is that it can hardly be measured directly. Three methods are usually used to quantify and measure it—(a) sociobehavioral indicators, (b) residual approach, and (c) functional neuroimaging studies [17]. Hence, studies should include not only measures of the status of the brain (reflecting brain alteration or pathology), but also clinical or cognitive performance (consequences of brain damage), and socio-behavioral indicators (e.g., an index of life-long experience/premorbid capacity) when assessing the role of CR. The goal is to be able to predict an individual's cognitive performance through the interaction between the proposed CR factors and the state of the brain/pathology.

Several studies have shown that CR proxies may decrease the rate of conversion to dementia in subjects with identical degrees of the pathological burden of AD [23, 24], and even have a protective role against the cognitive impairment associated with brain white-matter changes (WMC) or higher ventricular volume [25, 26] delaying the onset of clinical deficits [27]. Understanding the role of these proxies on the prediction of cognitive trajectories serves a two-fold objective, either it is disease prevention or disease diagnosis.

Different CR proxies have been identified [28], but recent systematic reviews indicate that education, occupational attainment, leisure activities, and social involvement are the most common indicators [29–31].

The number of years of formal education is the most consistently used across studies. A protective effect of education for age-associated cognitive decline appears to result in higher levels of CR [30, 32]. This is supported by strong positive associations between the number of years of formal education and crystallized measures (e.g., vocabulary) and EF, explaining, in the latter case, even more variance than age itself [33–35], compared with fluid abilities, such as processing speed, memory, or visuospatial abilities [34, 36, 37]. Robust scientific evidence also supports that lower-educated individuals are more likely to suffer from dementia in a wide range of settings [38]. For example, Contador et al. [39] found that living in a rural area (early and mid-life stages) increased the likelihood of dementia, with the risk being particularly high in people with low education. However, the effect of education on age-related cognitive changes remains controversial [40]. Kremen et al. [41] sought

to demonstrate that the impact of CR factors is primarily downstream of intellectual capacity. These researchers concluded that brain development is substantial during childhood and adolescence and that further education from the age of 20 years would contribute much less to brain development. Moreover, it should be considered that the quality of the educational experience is not the same for all individuals, which may influence its potential impact as a CR proxy.

The protective effect of education not only mediates the transition between normal and pathological aging but also between stages of cognitive impairment. Based on the hypothesis that less automatized cognitive domains (or those that did not achieve proper consolidation throughout life) may deteriorate sooner than more consolidated ones, a recent retrospective study aimed to investigate whether education modifies the profile of cognitive/executive performance (i.e., sustained and divided attention, inhibitory control, working memory, verbal, motor and graphomotor fluency, planning, abstract reasoning, and episodic memory) in Mild Cognitive Impairment (MCI). It was found that despite a similar pattern of cognitive decline in both higher and lower education groups, patients with higher education revealed a trend toward a higher proportion of abnormal performances (≤ −1.5 standard deviation on age- and education-adjusted normative scores) and a steeper decline in measures of sustained attention and episodic memory [42]. These findings suggest that patients with higher levels of education have a higher CR because they show a more pronounced decline in executive control that does not reflect differences in clinical disease staging [35, 43, 44]. On the opposite extreme of educational level, elderly illiterate subjects may be more vulnerable to cognitive decline and dementia, due to the lack of the protective effect of education [45–49].

It is worth noting that, although education is usually measured by the number of years of formal education, there may be other indicators that better capture its true impact. In a recent prospective longitudinal cohort study on aging and cognition, which recruited and followed 275 healthy community subjects seen in primary care settings, with 50 years or older, over a 5-year period, investigators found that being male, older, and with a lower age- and education-adjusted z-scores on divided attention/mental flexibility measures were significant independent predictors of cognitive impairment 5 years later. Moreover, vocabulary emerged as a stronger predictor of cognitive stability or decline than education, independently of their correlation [50]. This highlights the relevance of this measure by reflecting more accurately the degree of cognitive stimulation and intellectual enrichment that may account for subtle differences between subjects at the same educational level, particularly relevant in overall low-literacy populations.

Occupational and leisure activities may also have markedly significant protective effects on cognitive decline and dementia, especially for individuals whose jobs involve social interaction [51]. In fact, it is known that engagement in mentally stimulating activities throughout life may promote neural connectivity [52]. With respect to occupational activity, cognitively demanding work conditions are associated with a decreased risk of cognitive decline in older adults [53]. Middle-aged people at risk for AD (decreased hippocampal volume and increased brain atrophy) with greater occupational complexity (e.g., involving complex social interactions) maintained a similar level of cognitive performance as those with less pathology [51, 54]. However, since higher levels of education are usually associated with jobs that are more cognitively demanding, whether or not the protective effect of education is independent of the levels of work complexity in middle age remains controversial [55, 56]. Moreover, a synergistic effect of low education and occupation on the risk of developing AD

#### *The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline… DOI: http://dx.doi.org/10.5772/intechopen.104646*

was described by Stern et al. [57], particularly when it is combined with cognitively demanding work activity in adulthood [55, 57]. For instance, some studies indicate that level of literacy is a more accurate measure of CR than years of education [58], especially in those individuals from disadvantaged groups or with null/low educational attainment [39, 59]. Regarding involvement in leisure activities, it has also been associated with a reduced risk of AD [60, 61] and protective effects against cognitive decline [62, 63].

There seems to be evidence that lifestyle and the environment effectively regulate cognitive aging and that this regulation may be particularly relevant in the hippocampal-mediated memory functions in mammals. Although the causal nature of this relationship has not yet been established [64], studies in animal models seem to indicate that it may exist, but more clinical studies are needed to specifically understand how social involvement and integration can be used to prevent cognitive decline. Additionally, the mechanisms underlying this relationship seem to indicate a relevant role for growth factors, neuroinflammation, and neurogenesis processes. In this context, physical activity, for instance, has been identified as inducing neurogenesis due to its benefits on structural and functional plasticity in hippocampus-dependent learning and memory tasks. Accordingly, maintaining an active social life at older ages can improve CR and benefit cognitive function. This is especially relevant since some aspects, such as education or occupational complexity, developed at a young age and middle age cannot be modified. Social activity can contribute to an increased reserve even in a more advanced stage of life, with gains in cognitive performance. In fact, living alone was significantly associated with an increase in cognitive complaints and a significant predictor of future cognitive decline in specific linguistic/executive measures, such as verbal fluency over a 5-year follow-up [33, 65, 66]. Social interactions can be viewed as natural forms of cognitive stimulation and may play a relevant part in the stimulation of language skills, whereas living alone would represent a relative cognitive deprivation situation, with reduced cognitive stimulation and lower CR [67, 68]. Interventions that reduce social isolation at a more advanced stage can benefit cognitive function both directly and indirectly by building reserve, especially in individuals with low CR in middle age. This aspect has important implications for interventions suggesting that combating social isolation can contribute to a healthier cognition [69].
