Protective factors for dementia and AD have inhibitor Tofacitinib also been identified; these include high education and socioeconomic status in early life as well as a number of factors in adult life: high work complexity, rich social network, social engagement, mentally stimulating activity, nonsmoking, and regular physical exercise [5,23,24]. Living with a partner during mid-life has been associated with reduced risk of cognitive impairment and dementia later in life, suggesting that being in a relationship entails cognitive and social challenges that can increase the cognitive reserve [25]. Even at old ages, the active engagement in mental, physical, and social activities may postpone the onset of dementia, possibly by increasing the cognitive reserve [26].

In addition, several follow-up studies reported a decreased dementia risk associated with healthy dietary patterns and nutritional factors, such as high adherence to a Mediterranean diet or dietary intake of antioxidants (for example, vitamins E and C) and ??-3 polyunsaturated fatty acid (PUFA) (often measured as fish consumption) [27-31]. Cumulative and combined exposure to different risk factors can lead to modified effects on dementia/AD risk (Table ?(Table1).1). In the Finnish CAIDE (Cardiovascular Risk Factors, Aging and Incidence of Dementia) study, the risk of dementia has been evaluated in relation to a score (CAIDE Dementia Risk Score) combining mid-life risk factors, including low education and cardiovascular factors (that is, hypertension, obesity, hypercholesterolemia, and physical inactivity).

The risk of dementia increased as the score increased in a dose-response trend, making it possible to identify individuals who can greatly benefit from preventive intervention Cilengitide that targets vascular risk factors [32]. Similar findings have been reported for late-life exposures: in the Swedish Kungsholmen Project, the cumulative effect of vascular risk factors and vascular diseases on dementia/AD risk has been investigated in people who are at least 75 years old. These factors were aggregated according to two pathophysiological hypotheses: the brain hypoperfusion profile, defined by chronic heart failure, low pulse pressure, and low diastolic pressure, and the atherosclerosis profile, which included high systolic pressure, diabetes mellitus or prediabetes, and stroke. In both profiles, dementia/AD risk increased with increasing scores in a dose-response table 5 manner, suggesting a synergy of vascular risk factors in promoting dementia/AD also in advanced age [33]. The American Cardiovascular Health Cognition Study developed a Late-life Dementia Risk Index and also a brief version, which groups older adults in the three categories of low, moderate, and high risk of developing dementia.