On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae)

Mechanisms of “risk factors” for AD

The average age of diagnosis of AD in humans is around 50 years, with a progressive increase in incidence with increasing age. In fact nearly 50 % of individuals over the age of 85 is affected with this pathology [83, 89]. If well age itself is the single most important risk factor for sporadic AD, the development of this pathogenesis is multifactorial, with genetic, environmental and lifestyle factors implicated [83, 90]. There is an AD that runs in family history of dementia, primarily in those with early onset AD compared with those with late onset [83, 91, 92]. This familial form of AD is due to alterations in three specific genes: presenilin-1 (PS1, on chromosome 14), presenilin-2 (PS2, on chromosome 1) and amyloid precursor protein (APP) that can be inherited as an autosomal dominant disorder and accounts for less than 1 % of the total number of AD cases [79, 82, 92].

Gender is another risk factor for AD, being two to three times more common in females than males [92–94]. Female’s cognitive impairments may also be more severe than males [93–95]. These major sex differences in the incidence and age of onset of AD lies in that different hormone enter in the brain at different times [93]. Estrogens are neuroprotective with respect to neuronal degeneration [92, 96]. When estrogens levels drop at menopause the brain volume beings to decline, particularly in the hippocampus and parietal lobe (areas associated with memory and cognition) [92, 94, 97]. Studies with estrogen replacement therapy showed a delay of 29 % on the onset of AD and even an improve memory in Alzheimer’s patients [93, 96, 98]. On the other way, males are relatively spared because their continuing testosterone secretion is converted, to some extent, to estradiol in the brain (e.g., a men over the age of 60 have three times more circulating estadiol than women of a similar age) [92, 93, 99].

Epidemiological studies have demonstrated the role of environmental factors as diet, activities, or diseases (e.g., type 2 diabetes, hypertension, obesity), psychosocial factors (e.g., depression), as a well history of brain trauma (e.g., cerebrovascular disease, and vasculopathies) to influence both the onset and the progression of AD [83, 100]. For example, due to the high metabolic demand for energy in the brain, small perturbations in glucose metabolism are been expected to affect cognitive performance [79, 101]. Type 2 diabetes (T2DM) has been linked with lower levels of neuronal growth factors, a decreased brain volume and also as an important risk factor for AD development [100, 102]. Lifestyle factors like obesity, poor diet and sedentary behavior, in association with heredity represent the major risk factors for development of insulin resistance, a proximal cause of T2DM [103, 104] and other hypertension, dyslipidemia and cardiovascular disease [86, 105]. There is substantial evidence in animal studies and humans linking diet induced obesity to development and progression of cognitive dysfunction such that higher adiposity means a major risk of developing memory impairment [86, 106]. Furthermore, studies have confirmed association between an increased body mass index with decreased brain volume [107]. Other clinical studies outlined that overweight in humans is associated with reductions in several brain areas involved in the regulation of taste, reward, and behavioral control [108]. Altogether insulin resistance pathology and obesity may lead to much higher incidence and prevalence of AD (86; 104). Other medical conditions that can increase the risk of developing AD include the presence of other disease processes such as Parkinson’s disease, Huntington’s disease, multiple sclerosis and HIV. Down syndrome and some other learning disabilities also increase a person’s risk of dementia [91, 109].

Additional studies suggest that lack of social affiliation (e.g., small social network, participating in small quantitative and low quality of social relations) or social isolation (i.e., physical or contact absence of other members within a social species) has been associated with rapid decline of cognitive function and may contribute to develop AD in late life [110, 111]. Furthermore, investigations of the role of the social environment in health promoting from the stand point of cognitive develop showed that increasing positive social interactions led to improve cognition and buffering against to stressors [112, 113]. For example, animals subject to social isolation developed cognitive impairment and present an early onset and accelerate progression of AD via enhancing activity of certain proteins which plays important role in the production of A? peptide and phosphorylation of tau [114, 115]. In humans community, socially isolated individuals have increased risk of developing AD and two to four times increased risk of dead compared with individuals with social ties to friends and relatives [110, 114]. Thus, a high lifelong level of social attachments represents dynamic and complex social systems that affect health outcomes, particularly attaining environmental protection against AD.

Taken together, these data suggest that genetic and environmental influences could be one mechanism behind the wide variation in the onset and progression of AD.