Lifestyle-related risk factors in dementia and mild cognitive impairment : a population-based study

As an increasing number of individuals survive into advanced age, dementia and milder cognitive impairments takes on growing public health importance. The aetiology of dementia and Alzheimer's disease (AD), which is the most common cause of dementia, is considered to be multifactorial, resulting from both genetic and environmental factors. The present thesis project aimed at obtaining a comprehensive understanding of the role of lifestyle-related factors in the development of dementia and cognitive impairment. Special attention was paid to possible interactions between lifestyle-related and genetic risk factors. The general hypothesis was that a healthy lifestyle could reduce the risk of dementia and cognitive impairment. All five studies were based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project. The participants in the CAIDE project were derived from four independent population-based random samples studied within the framework of the North Karelia Project and the FINMONICA study in 1972, 1977, 1982 or 1987. A random sample of 2000 individuals aged 65-79 years and living in two geographically defined areas in Kuopio and Joensuu in eastern Finland were invited for the reexamination in 1998, and altogether 1449 people (73 %) participated. In study 1, obesity at midlife was associated with an increased risk of dementia and AD. Midlife obesity, high cholesterol, and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each parameter, and they increased the risk additively. In study 2, we observed a U-shaped association between midlife alcohol drinking and the risk of mild cognitive impairment (MCI) in late-life, so that the participants who did not drink alcohol, as well as those who drank alcohol frequently, had a two-fold risk of having MCI when compared with those participants who drank alcohol infrequently. The presence of the apolipoprotein E (ApoE) epsilon4 allele modified the association between alcohol drinking and dementia: ApoE epsilon4 carriers showed an increased risk of dementia with increasing alcohol drinking frequency, whereas this was not the case for the ApoE epsilon4 non-carriers. In study 3, we investigated the relationship of midlife alcohol drinking to cognitive functions in late-life among the non-demented individuals. The participants who did not drink alcohol at midlife, had poorer performance compared to infrequent and frequent drinkers in episodic memory, psychomotor speed, and executive function in late-life. In study 4 low income level in late-life but not at midlife was related to the risk of dementia. Dementia was also associated with decreasing income level from midlife to old age. Low educational level and the ApoE FA allele independently increased the risk of dementia. In study 5 we examined whether the association between education and dementia was due to the presence of unhealthier lifestyles or more cardiovascular risk factors among the less educated persons. High education was associated with a lower risk of dementia and AD, and it remained unchanged after adjustments for a wide range of lifestyle factors. In summary, this set of studies showed that unhealthy lifestyle-related factors at midlife, such as obesity, hypertension and hypercholesterolemia increase the risk of developing dementia and AD later in life. Especially among ApoE epsilon4 allele carriers, alcohol drinking increases the risk of dementia. On the other hand, in non-demented individuals, alcohol drinkers exhibit better cognitive performance compared to abstainers. However, it is not clear whether this association is causal, or what is the optimal level of alcohol consumption to achieve the best cognitive function. High education is associated with a decreased risk of dementia whereas a high income level at midlife is not a contributary factor. A reduction in relative income level between midlife and late-life might well be a consequence of the dementing disease process. Educated persons may have a greater cognitive reserve that leads to a postponement of the clinical manifestation of dementia. The unhealthy lifestyle options may independently contribute to the depletion of this reserve or directly induce the pathologic processes underlying dementia and AD