Lifestyle Factors and Risk of Dementia

Despite a half century of scientific study, the cure for Alzheimer’s disease remains elusive and therapies are virtually ineffective. The disease is common, rising exponentially with older age, [1] and its central characteristic, loss in memory and other cognitive abilities, is one of the most feared consequences of aging. The human and economic costs loom large as the oldest age groups continue to grow, foretelling a public health crisis. Whereas the therapeutic drug trials conducted in recent years have experienced a 99.6% failure rate, [2] far greater success has been achieved in the identification of protective risk factors and lifestyle interventions. Among these are diet, physical activity, alcohol consumption, positive social encounters and cognitive training. In this review, we highlight the key studies and findings in this important area of dementia prevention.


Introduction
Despite a half century of scientific study, the cure for Alzheimer's disease remains elusive and therapies are virtually ineffective. The disease is common, rising exponentially with older age, [1] and its central characteristic, loss in memory and other cognitive abilities, is one of the most feared consequences of aging. The human and economic costs loom large as the oldest age groups continue to grow, foretelling a public health crisis. Whereas the therapeutic drug trials conducted in recent years have experienced a 99.6% failure rate, [2] far greater success has been achieved in the identification of protective risk factors and lifestyle interventions. Among these are diet, physical activity, alcohol consumption, positive social encounters and cognitive training. In this review, we highlight the key studies and findings in this important area of dementia prevention.

Diet
Since the earliest reported studies of diet and dementia twenty years ago, a number of diet components have been identified in the development of the disease, including seafood, [3,4] vegetables (especially leafy greens), [5][6][7] berries, [8,9] nuts, [7-10] extra virgin olive oil, [11] and nutrients such as vitamin E, [12,13] folate, [14,15] n-3 fatty acids, [16] carotenoids [13,17,18] and flavonoids [13,19,20]. Fat composition that is higher in unsaturated fats also appears to be important for brain health [21][22][23]. More recent studies have focused on dietary patterns, with many finding decreased risk of dementia with various healthy diets including the Mediterranean [24][25][26] and DASH (Dietary Approach to Stop Hypertension) diets [25,27]. It should be noted that this literature is by no means consistent; about half of the prospective studies of healthy diet patterns reported no association with dementia outcomes [28].
Interpretations of study findings are hampered by methodological flaws in the analyses of the nutritional data. A new diet called MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) that was created specifically for brain health was significantly associated with lower risk of Alzheimer's disease [25] and with slower cognitive decline [29], and is currently being tested in a randomized trial.

Alcohol Consumption
A number of prospective epidemiologic studies world-wide have examined the relation of self-reported alcohol consumption to risk of developing dementia and cognitive decline. The findings from these studies indicate a U-shaped association, with abstainers and heavy drinkers at increased risk of impairment compared with those who consume light to moderate amounts [30][31][32][33][34]. Determination of the dose level associated with the lowest risk is complicated by cultural differences both in alcohol consumption patterns and in reporting stigma, but appears to be somewhere in the range of 1 to 6 drinks weekly up to 2 drinks per day in several meta-analyses [45][46][47]. Three of the studies reported protective relations with wine consumption only [35,36,44]. An international randomized trial investigating the effects of moderate alcohol consumption on cardiovascular outcomes is currently underway with plans for cognitive outcomes as well.

Physical Activity
Moderate to vigorous physical activity at a frequency that is roughly equivalent to one to three times per week has been associated with slower cognitive decline [48][49][50] and with lower risk of dementia by about 40 to 60% compared with little or no activity [51][52][53][54][55][56] in multiple prospective studies. There have been a number of randomized intervention trials, but unfortunately, the majority of these trials were small (n≤155) and of short duration (≤1 year) and thus likely underpowered to observe significant differences between the groups [57][58][59][60][61][62]. The largest trial reported to date investigated the effects of a 2-year moderate physical activity program consisting of walking, strength, and flexibility on physical and cognitive performance in 1,476 older adults [63]. No overall difference was observed in cognition compared with the health education control group, however, among diabetics the moderate physical activity intervention had protective effects on overall cog-nition as well as delayed memory. Other trials of physical activity are currently underway that should clarify whether aerobic forms of exercise are required for protective benefit [59].

Cognitive and Social Activities
A developed body of literature provides evidence that participation in cognitive and social activities helps to maintain brain functioning into old age. The theory of cognitive reserve, whereby greater neural connections allow the brain to function despite the presence of neuropathologies, has been proposed as the underlying biologic mechanism for the protective relations of these activities [30,[33][34][35][36][37][38][39][40][41][42]64]. In prospective epidemiological studies, higher participation in cognitive activities such as reading, playing musical instruments and board games, and doing crossword and other puzzles, has been associated with lower risk of dementia [65-72] and slower decline in cognitive abilities [73,74]. Multiple randomized trials of cognitive training interventions support the findings of the observational studies [75][76][77]. A meta-analysis of 31 randomized trial found that cognitive training improved performance on tests of executive function (working memory and processing speed), memory (face-name recall, immediate recall, paired associates) and subjective cognitive function [78]. To date, it is not clear, however, whether cognitive training improves everyday functioning.
Greater number and frequency of social contacts, providing they are positive interactions, have also been associated with lower risk of dementia [70,[79][80][81][82]