various single dietary components have been linked with cognitive impairment and dementia / alzheimer 's disease ( ad ) . for example , it has been reported that a diet rich in saturated fatty acids ( sfas ) and cholesterol may increase the risk of dementia / ad , whereas polyunsaturated fatty acids ( pufas ) and fish may be protective . also , higher dietary intake of vitamin e , vitamin c , and flavonoids , and higher levels of vitamin b12 and folate have been associated with a reduced risk of cognitive impairment and dementia / ad , although these findings are not uniform across studies . furthermore , moderate coffee drinking   and alcohol consumption   have been suggested to decrease the risk of cognitive impairment and dementia / ad , but these findings are also not unequivocal . so far , the main focus of studies on diet and dementia has been on single dietary components . however , single nutrients are not consumed in isolation but as a part of a dietary pattern . examining the role of single nutrients / food items is complicated because they are strongly correlated . also , the many possible interactions between nutrients are difficult to estimate . therefore , examining dietary patterns rather than single nutrients might be more useful in understanding the role of diet in chronic diseases . a healthy diet has been linked , among other factors , with a reduced risk of mortality from cardiovascular diseases and cancers , as well as lower incidences of parkinson 's disease and diabetes . only three previous longitudinal studies have investigated the relationship between a healthy diet ( including several dietary components ) and dementia / ad . a recent report from the washington heights - inwood columbia aging project ( whicap ) among elderly persons found that a dietary pattern rich in several single nutrients earlier identified as reducing the risk of ad was associated with a reduced risk of ad during a follow - up of 4 years . an earlier report from the same project found that higher adherence to the mediterranean diet was associated with a decreased risk of ad development   as well as with lower mortality in ad . in the three - city ( 3c ) study among elderly persons , the mediterranean diet was associated with a slower decline in the mini - mental state examination ( mmse ) , but not with dementia / ad risk over a 5-year period . all these previous studies were conducted among elderly persons , and follow - up times were relatively short . today , no studies exist on whether a healthy diet as early as in midlife has an effect on the risk of developing dementia later on . the aim of our study was to investigate the associations of a midlife healthy diet with the development of dementia and ad later in life in a population - based cohort of people living in eastern finland . the healthy - diet index was constructed using information on both beneficial and detrimental components of individuals midlife diet . the participants of the cardiovascular risk factors , aging and dementia ( caide ) study were randomly selected from survivors of population - based random samples firstly studied within the north karelia project and the finmonica study in 1972 , 1977 , 1982 , or 1987 ( baseline , midlife visit ) . a random sample of 2,000 survivors aged 6579 years at the end of 1997 and living in the study area in eastern finland ( in joensuu or kuopio ) 1,409 ( 70.5% ) individuals completed the follow - up examination ( late - life visit ) . for the current study , we used the sub - samples , who were first enrolled in 1982 or 1987 , because of the more extensive dietary information available . these 239 women ( 62.1% ) and 146 men ( 37.9% ) had a mean ( sd ) age of 56.7 ( 4.0 ) years at the time of their midlife examination , and 70.6 ( 3.7 ) years at the time of their late - life examination in 1998 . all participants gave written informed consent in 1998 , and the local ethical committee of kuopio university and kuopio university hospital approved the study . the survey methods used during the baseline visit were carefully standardized and complied with international recommendations . in brief , the survey included an exhaustive self - administered questionnaire on health behavior ( including dietary habits ) , health status and medical history . systolic ( sbp ) and diastolic blood pressure ( dbp ) , height and weight were measured , body mass index ( bmi ) was calculated , and a venous blood sample was taken to determine serum cholesterol . during the follow - up examination in 1998 , the survey methods followed those utilized in the previous surveys in all aspects . additionally , the apolipoprotein e ( apoe ) genotype of participants was determined with a method described by tsukamoto et al . , and the cognitive status was assessed . global cognitive function was assessed first with the mmse . for the diagnosis of dementia , a three - step protocol ( screening , clinical , and differential diagnostic phase ) was used ; individuals scoring 24 on the mmse were addressed for further diagnostic examination . the diagnosis of dementia was based on dsm - iv criteria , and probable and possible ad was diagnosed according to the nincds - adrda criteria . of the 1982 and 1987 sub - population , a total of 13 persons met the diagnosis of dementia , out of whom 11 had ad . all patients with ad showed generalized or medial temporal atrophy , and none showed appreciable vascular pathology on magnetic resonance scans . isolated minor lacunae or periventricular white matter signal changes were not considered as exclusion criteria for ad . all patients with ad scored 4 on the hachinski ischemia scale . when diagnoses derived from the patient records of the non - participants in the follow - up examination were taken into account , dietary habits were inquired with a survey questionnaire consisting of approximately 20 mostly qualitative or frequency - based multiple choice questions , but some questions , e.g. the consumption of coffee and eggs , were assessed quantitatively at the midlife examination . the usual number of bread slices consumed per day , and the type and amount of spread used was inquired during the examination . for calculating the healthy - diet index , we modified the method that trichopoulou et al a value of 0 or 1 was assigned to each of the 18 food groups , using mainly sex - specific medians as cutoffs . for beneficial components [ vegetables and roots , berries and fruits , bread , fish , coffee drinking , monounsaturated fatty acids ( mufas ) and pufas from milk products and spreads ] , persons whose consumption was below the median were assigned a value of 0 and persons whose consumption was at or above the median were assigned a value of 1 . for components presumed to be unhealthy ( sausage foods , eggs , candies , sweet soft drinks , sugar lumps in coffee , salty fish , and sfas from milk products and spreads ) , points were given vice versa ( below the median = 1 , at or above the median = 0 ) . the consumption of salty fish was available for the 1982 sample only , and the consumption of fish for the 1987 sample only . in the final index , the information that was available on these two variables was used . for alcohol drinking , a value of 1 was assigned to persons with moderate alcohol consumption and a value of 0 to persons not consuming alcohol or consuming abundantly ( moderate and abundant were defined with sex - specific median values among drinkers ) . for the use of salt on the dining table , a value of 1 was given to persons who were not adding salt to the meals and a value of 0 to the other categories ( i.e. adding salt when the food is not salty enough or almost always before tasting ) . finally , we also included fats used for cooking and baking in the household into our healthy - diet index : using vegetable oil or margarine was assigned a value of 1 and butter or a butter - oil mixture a value of 0 . there were some missing values for some of the food groups ( 019 persons with missing values apart from the variable after adding up the points of every food category , we received the total healthy - diet index that could range theoretically from 0 ( minimal adherence to healthy diet ) to 17 ( maximal adherence ) . the healthy - diet index was dichotomized based on median values : 08 points ( low adherence to healthy diet ) and > 8 points ( high adherence to healthy diet ) . logistic regression models were used to analyze the independent effect of a healthy diet on the risk of dementia and ad so that the group with low adherence to a healthy diet served as the reference group . model 1 was adjusted for age , sex , education , follow - up time , community of residence , and apoe 4 carrier status . model 2 was adjusted additionally for cardiovascular risk factors including midlife sbp , serum total cholesterol , bmi , and the presence of late - life myocardial infarction / stroke / diabetes mellitus . model 3 was adjusted additionally for midlife leisure - time physical activity and smoking . for mmse , analysis of covariance ( ancova ) was applied with similar adjustments as for dementia and ad . for the non - participants , logistic regression analyses were done to the appropriate extent ( model 1 was adjusted for age , sex , education , and community of residence ; model 2 was adjusted additionally for midlife sbp , serum total cholesterol and bmi , and model 3 was adjusted additionally for midlife leisure - time physical activity and smoking ) . the participants of the cardiovascular risk factors , aging and dementia ( caide ) study were randomly selected from survivors of population - based random samples firstly studied within the north karelia project and the finmonica study in 1972 , 1977 , 1982 , or 1987 ( baseline , midlife visit ) . a random sample of 2,000 survivors aged 6579 years at the end of 1997 and living in the study area in eastern finland ( in joensuu or kuopio ) 1,409 ( 70.5% ) individuals completed the follow - up examination ( late - life visit ) . for the current study , we used the sub - samples , who were first enrolled in 1982 or 1987 , because of the more extensive dietary information available . these 239 women ( 62.1% ) and 146 men ( 37.9% ) had a mean ( sd ) age of 56.7 ( 4.0 ) years at the time of their midlife examination , and 70.6 ( 3.7 ) years at the time of their late - life examination in 1998 . all participants gave written informed consent in 1998 , and the local ethical committee of kuopio university and kuopio university hospital approved the study . the survey methods used during the baseline visit were carefully standardized and complied with international recommendations . in brief , the survey included an exhaustive self - administered questionnaire on health behavior ( including dietary habits ) , health status and medical history . systolic ( sbp ) and diastolic blood pressure ( dbp ) , height and weight were measured , body mass index ( bmi ) was calculated , and a venous blood sample was taken to determine serum cholesterol . during the follow - up examination in 1998 , the survey methods followed those utilized in the previous surveys in all aspects . additionally , the apolipoprotein e ( apoe ) genotype of participants was determined with a method described by tsukamoto et al . , and global cognitive function was assessed first with the mmse . for the diagnosis of dementia , a three - step protocol ( screening , clinical , and differential diagnostic phase ) was used ; individuals scoring 24 on the mmse were addressed for further diagnostic examination . the diagnosis of dementia was based on dsm - iv criteria , and probable and possible ad was diagnosed according to the nincds - adrda criteria . of the 1982 and 1987 sub - population , a total of 13 persons met the diagnosis of dementia , out of whom 11 had ad . all patients with ad showed generalized or medial temporal atrophy , and none showed appreciable vascular pathology on magnetic resonance scans . isolated minor lacunae or periventricular white matter signal changes were not considered as exclusion criteria for ad . all patients with ad scored 4 on the hachinski ischemia scale . when diagnoses derived from the patient records of the non - participants in the follow - up examination were taken into account , the number of demented persons increased to 29 . dietary habits were inquired with a survey questionnaire consisting of approximately 20 mostly qualitative or frequency - based multiple choice questions , but some questions , e.g. the consumption of coffee and eggs , were assessed quantitatively at the midlife examination . the usual number of bread slices consumed per day , and the type and amount of spread used was inquired during the examination . for calculating the healthy - diet index , we modified the method that trichopoulou et al a value of 0 or 1 was assigned to each of the 18 food groups , using mainly sex - specific medians as cutoffs . for beneficial components [ vegetables and roots , berries and fruits , bread , fish , coffee drinking , monounsaturated fatty acids ( mufas ) and pufas from milk products and spreads ] , persons whose consumption was below the median were assigned a value of 0 and persons whose consumption was at or above the median were assigned a value of 1 . for components presumed to be unhealthy ( sausage foods , eggs , candies , sweet soft drinks , sugar lumps in coffee , salty fish , and sfas from milk products and spreads ) , points were given vice versa ( below the median = 1 , at or above the median = 0 ) . the consumption of salty fish was available for the 1982 sample only , and the consumption of fish for the 1987 sample only . in the final index , , a value of 1 was assigned to persons with moderate alcohol consumption and a value of 0 to persons not consuming alcohol or consuming abundantly ( moderate and abundant were defined with sex - specific median values among drinkers ) . for the use of salt on the dining table , a value of 1 was given to persons who were not adding salt to the meals and a value of 0 to the other categories ( i.e. adding salt when the food is not salty enough or almost always before tasting ) . finally , we also included fats used for cooking and baking in the household into our healthy - diet index : using vegetable oil or margarine was assigned a value of 1 and butter or a butter - oil mixture a value of 0 . there were some missing values for some of the food groups ( 019 persons with missing values apart from the variable after adding up the points of every food category , we received the total healthy - diet index that could range theoretically from 0 ( minimal adherence to healthy diet ) to 17 ( maximal adherence ) . the healthy - diet index was dichotomized based on median values : 08 points ( low adherence to healthy diet ) and > 8 points ( high adherence to healthy diet ) . all statistical analyses were conducted using pasw statistics , version 17 ( spss inc . , chicago , ill . logistic regression models were used to analyze the independent effect of a healthy diet on the risk of dementia and ad so that the group with low adherence to a healthy diet served as the reference group . model 1 was adjusted for age , sex , education , follow - up time , community of residence , and apoe 4 carrier status . model 2 was adjusted additionally for cardiovascular risk factors including midlife sbp , serum total cholesterol , bmi , and the presence of late - life myocardial infarction / stroke / diabetes mellitus . model 3 was adjusted additionally for midlife leisure - time physical activity and smoking . for mmse , analysis of covariance ( ancova ) was applied with similar adjustments as for dementia and ad . for the non - participants , logistic regression analyses were done to the appropriate extent ( model 1 was adjusted for age , sex , education , and community of residence ; model 2 was adjusted additionally for midlife sbp , serum total cholesterol and bmi , and model 3 was adjusted additionally for midlife leisure - time physical activity and smoking ) . the composition of the caide midlife healthy - diet index with the sex - specific cutoff values is given in table 1 . in our population , the scores ranged from 2 to 14.5 , with no subjects having the absolute lowest or highest possible scores . at midlife , persons with a high adherence to a healthy diet were more educated compared with persons with a low adherence to a healthy diet . dbp and bmi were higher among those with a low adherence to a healthy diet , and also the proportion of persons with a sedentary lifestyle was higher in this group . persons who had the healthiest diet at midlife had the lowest occurrence of dementia and ad late in life ( table 2 ) . the non - participants of the follow - up examination were older , less educated , and had higher sbp , dbp , and serum total cholesterol at midlife than the participants . they were also more often demented ( diagnoses from patient records ) than the participants . altogether 59.0% of the non - participants belonged to the group with a low adherence to a healthy diet compared to 53.7% of the participants ; however , the difference was not statistically significant ( p = 0.29 ) . the subjects with a high adherence to a healthy diet performed better on global cognitive function than those with a low adherence to a healthy diet [ model 3 : mean mmse ( standard error , se ) 26.2 ( 0.2 ) vs. 25.6 ( 0.2 ) , respectively , p = 0.02 ] . those persons who ate healthiest had an 8690% decreased risk of dementia and a 9092% decreased risk of ad compared with persons whose diet was least healthy ( table 3 ) . adjustments for various confounders did not change the results . when we rerun the analyses for dementia also including diagnoses from the patient records for the non - participants in the follow - up , persons in the high - adherence group showed a tendency towards a decreased risk of dementia compared with the group with a low adherence to a healthy diet ( model 1 : or 0.5 , 95% ci 0.231.27 ; model 2 : or 0.27 , 95% ci 0.071.00 ; model 3 : or 0.28 , 95% ci 0.071.09 ) . our findings indicate that adherence to a healthy diet already at midlife is associated with a decreased risk of dementia and ad later in life . although a healthy diet is an important determinant for the level of several risk factors for dementia , e.g. blood pressure , serum cholesterol , diabetes , and obesity , the effect of a healthy diet remained highly significant even after adjustments for several potential confounding or mediating factors , suggesting an independent effect of the healthy diet . there is only one previous study on dietary patterns and dementia showing the beneficial effect of the mediterranean diet   and of a dietary pattern low in ad - related nutrients , and our results are in accordance with these findings . our study is the first to show that a healthy diet as early as at midlife is important for the prevention of dementia and ad in the elderly . furthermore , our study extends the findings to more comprehensive dietary patterns than those captured by the mediterranean - diet index only . our caide healthy - diet index differs from the methods used in previous studies in that we were not able to take into account the total energy intake when calculating the index , and many of the variables were frequency based . on the other hand , our approach gives very practical information on the foods included , making it simple for a person to calculate his or her adherence to the healthy diet . in the calculation of the index , the median values were used as cutoffs , and general dietary recommendations were used to define what was healthy and what was unhealthy . its effect could be due to the specific characteristics of single beneficial nutrients and/or their combination . oxidative stress may contribute to the neuronal damage in ad , and reduced oxidative stress related to a healthy diet could explain the results . folate deficiency in diet can lead to high homocysteine levels , which has direct neurotoxic effects in cell lines and animal models . the combination of vitamins e and c   has been shown to promote neuronal survival in rat brains . furthermore , unsaturated fatty acids may influence the pathogenesis of ad by modulating , for example , the composition and fluidity of neuronal membranes and preventing neuro - inflammation . a mediterranean / healthy diet has also been associated with cardiovascular risk factors , including hypertension , dyslipidemia , diabetes , and obesity . in our analyses , we took into account several vascular risk factors and diseases , but an independent effect of a healthy diet still remained . additionally , dietary habits are related to other social and lifestyle - related factors , and thus the association might be due to such confounding effects . in our analyses , we adjusted for several possible confounding factors , and the results remained unchanged . the trials conducted to prevent ad that have been carried out to test single nutritional components , such as vitamin e or c supplements , have yielded disappointing results . so far , trials with a more complete nutritional intervention have not been done . for other outcomes , such as cardiovascular disease and diabetes , also the trials on single nutrients have not been very successful , whereas trials with more comprehensive dietary interventions have shown positive effects . it would be interesting to see if comprehensive dietary interventions would also prevent or postpone dementia in susceptible persons . one multidomain trial , the finnish geriatric intervention study to prevent cognitive impairment and disability ( finger ) , also including dietary intervention , has recently been initiated , and the results will eventually shed new light on this issue . first , we had a population - based design , high participation rates ( both at baseline and even at the re - examination ) , and both women and men were represented , all of which factors increase the generalizability of our findings . second , dietary information was collected with the previously validated food frequency questionnaire ( the primary method of dietary assessment in epidemiologic studies ) because it refers to a whole year and is easy to complete . third , the dietary information was collected already at midlife ( on average 14 years before the diagnosis of dementia ) , and therefore it was not prone to bias caused by subclinical dementia . reliance on self - report for data of dietary habits may constitute a limitation , although we do not believe that this would have led to systematic errors in reporting dietary habits ( i.e. the future dementia did not affect how dietary habits were reported ) . we did not have complete quantitative information , or information on some of the potentially interesting dietary factors ( e.g. total energy intake , fiber intake , or intake of various vitamins ) . fatty acid intake was derived from spreads and milk only , which constituted approximately 50% of the total dietary fat intake in finland at the time of the midlife examinations . however , due to the fact that many nutrients and dietary behaviors were included in the index , we were able to categorize people into groups of high and low adherence to a recommended diet in our population . whether our caide healthy - diet index is a valid tool for assessing the risk of dementia in other populations has still to be evaluated . we can not completely exclude the possibility of residual confounding due to measurement error in the assessment of confounding factors , or the potential role of some unmeasured factors . however , we adjusted our analyses for a large number of potential confounding factors , but our results still remained significant . our sample was relatively small , which led to large cis , and we were not able to conduct stratified analyses in a reliable way . the non - participants of the follow - up study were more often demented ( diagnoses from patient records ) than the participants , but there were no significant differences in adherence to a healthy diet at midlife between the groups . therefore , it is unlikely that selective non - participation would have biased our results . its effect could be due to the specific characteristics of single beneficial nutrients and/or their combination . oxidative stress may contribute to the neuronal damage in ad , and reduced oxidative stress related to a healthy diet could explain the results . folate deficiency in diet can lead to high homocysteine levels , which has direct neurotoxic effects in cell lines and animal models . the combination of vitamins e and c   has been shown to promote neuronal survival in rat brains . furthermore , unsaturated fatty acids may influence the pathogenesis of ad by modulating , for example , the composition and fluidity of neuronal membranes and preventing neuro - inflammation . a mediterranean / healthy diet has also been associated with cardiovascular risk factors , including hypertension , dyslipidemia , diabetes , and obesity . in our analyses , we took into account several vascular risk factors and diseases , but an independent effect of a healthy diet still remained . additionally , dietary habits are related to other social and lifestyle - related factors , and thus the association might be due to such confounding effects . in our analyses , we adjusted for several possible confounding factors , and the results remained unchanged . the trials conducted to prevent ad that have been carried out to test single nutritional components , such as vitamin e or c supplements , have yielded disappointing results . so far , trials with a more complete nutritional intervention have not been done . for other outcomes , such as cardiovascular disease and diabetes , also the trials on single nutrients have not been very successful , whereas trials with more comprehensive dietary interventions have shown positive effects . it would be interesting to see if comprehensive dietary interventions would also prevent or postpone dementia in susceptible persons . one multidomain trial , the finnish geriatric intervention study to prevent cognitive impairment and disability ( finger ) , also including dietary intervention , has recently been initiated , and the results will eventually shed new light on this issue . first , we had a population - based design , high participation rates ( both at baseline and even at the re - examination ) , and both women and men were represented , all of which factors increase the generalizability of our findings . second , dietary information was collected with the previously validated food frequency questionnaire ( the primary method of dietary assessment in epidemiologic studies ) because it refers to a whole year and is easy to complete . third , the dietary information was collected already at midlife ( on average 14 years before the diagnosis of dementia ) , and therefore it was not prone to bias caused by subclinical dementia . reliance on self - report for data of dietary habits may constitute a limitation , although we do not believe that this would have led to systematic errors in reporting dietary habits ( i.e. the future dementia did not affect how dietary habits were reported ) . we did not have complete quantitative information , or information on some of the potentially interesting dietary factors ( e.g. total energy intake , fiber intake , or intake of various vitamins ) . fatty acid intake was derived from spreads and milk only , which constituted approximately 50% of the total dietary fat intake in finland at the time of the midlife examinations . however , due to the fact that many nutrients and dietary behaviors were included in the index , we were able to categorize people into groups of high and low adherence to a recommended diet in our population . whether our caide healthy - diet index is a valid tool for assessing the risk of dementia in other populations has still to be evaluated . we can not completely exclude the possibility of residual confounding due to measurement error in the assessment of confounding factors , or the potential role of some unmeasured factors . however , we adjusted our analyses for a large number of potential confounding factors , but our results still remained significant . our sample was relatively small , which led to large cis , and we were not able to conduct stratified analyses in a reliable way . the non - participants of the follow - up study were more often demented ( diagnoses from patient records ) than the participants , but there were no significant differences in adherence to a healthy diet at midlife between the groups . therefore , it is unlikely that selective non - participation would have biased our results . to conclude , our results suggest that a healthy diet at midlife may be associated with a decreased risk of dementia / ad later in life . these findings highlight the importance of dietary patterns ( instead of single nutrients ) and might open possibilities to more effectively prevent or delay the onset of dementia / ad . the caide healthy - diet index might be used as a tool to distribute information on the importance of dietary patterns in connection with the occurrence of dementia . however , this finding needs to be confirmed , and the index could be improved by large cohort studies with more accurate dietary data . identification of mechanisms of how dietary habits exert their protection against dementia / ad might help in the development of new therapies for these diseases . she has received royalties from publishing and being an editor and writer for a book on memory disorders in finland , published by duodecim . m.k . received honoraria for serving on the scientific advisory board of elan and pfizer , and serves as a speaker on scientific meetings organized by janssen , novartis , and pfizer .
aimto study long - term effects of dietary patterns on dementia and alzheimer 's disease ( ad).methodsof 525 subjects randomly selected from population - based cohorts surveyed at midlife , a total of 385 ( 73% ) subjects were re - examined 14 years later in the caide study . 
 a healthy - diet index ( range 017 ) was constructed including both healthy and unhealthy dietary components.resultspersons with a healthy diet ( healthy - diet index > 8 points ) had a decreased risk of dementia ( or 0.12 , 95% ci 0.020.85 ) and ad ( or 0.08 , 95% ci 0.010.89 ) compared with persons with an unhealthy diet ( 08 points ) , adjusting for several possible confounders.conclusionshealthy diet at midlife is associated with a decreased risk of dementia / ad in late life . 
 these findings highlight the importance of dietary patterns and may make more effective measures for dementia / ad prevention or postponement possible .