These indices include information from different domains, including demographic factors (age), genetics (presence of the apolipoprotein E (ApoE) ??4 allele), lifestyle (BMI of less than 18.5 and lack of alcohol consumption), comorbid vascular conditions (internal carotid artery thickening, angina, coronary artery bypass surgery, stroke, following website and peripheral artery disease), evidence of brain abnormalities shown by magnetic resonance imaging (white matter diseases or enlarged ventricles), cognitive test scores, and physical performances [34,35]. The combined effect of genetic-environmental or environmental-environmental joint exposures may also lead to the attenuation of the dementia risk. Population-based studies suggest an effect modification for the ApoE ??4 allele, the most important genetic risk factor for sporadic AD.

ApoE ??4 carriers seem more vulnerable to risk factors like alcohol drinking, smoking, physical inactivity, and high intake of saturated fat, indicating that people with genetic susceptibility may reduce their initial AD risk by lifestyle interventions (that is, physical activity, sufficient intake of PUFA, and avoiding excess alcohol drinking and smoking) [36]. Furthermore, it has been shown that high education may reduce dementia risk among ApoE ??4 allele carriers [37]. In regard to the interactions among modifiable risk factors, results from the Kungsholmen Project suggested that complexity of work with data and people was related to a decreased dementia risk and that the highest level of work complexity may modulate the increased dementia risk due to low education [23].

In conclusion, even though for some risk and protective factors the role in dementia and AD needs to be clarified, evidence from observational studies points at different modifiable factors that can be managed in order to prevent or delay dementia onset. Moreover, epidemiological findings strongly suggest that the life-course approach model and the multifactorial nature of dementia and AD should be considered when planning any preventive strategy. Prevention of dementia: current evidence from interventional studies Interventional studies on dementia and AD prevention have tested different medications, including statins, antihypertensive drugs, estrogens alone or in combination with progestin (hormone replacement therapy, or HRT), non-steroidal anti-inflammatory drugs (NSAIDs), and nutraceuticals (folate, Ginkgo biloba, and vitamins B12, C, and E).

For all of these compounds, the GSK-3 protective effects suggested by observational studies have sellekchem not been confirmed in randomized controlled trials (RCTs), the results of which are inconsistent or even suggest a detrimental effect on cognition (for example, NSAIDs and HRT) [38-41]. Few interventional studies implementing non-pharmacological approaches have been carried out.