tobacco use remains to be the leading cause of preventable death around the world ( 1 ) . it is associated with an increased risk of various diseases , including respiratory problems , cardiovascular disorders and cancers ( 2 , 3 ) . being the key determinant of tobacco addiction , nicotine dependence ( nd ) is one of the major barriers of successful smoking cessation ( 46 ) . the incidence of smoking cessation varies with age ( 7 ) . the quitting ratio in young ( 2131 years old ) and old ( 5160 years old ) adults appears to be greater than that in middle aged ( 3150 years old ) group . previous studies conducted in south korea ( 8) and china ( 9 ) demonstrate that nd has an inverse u - shaped relationship with age , with the peak at 50 years of age . that supports and may partially account for what underlies the cessation - age trend found by fidler et al . however , the number of studies on the relationship between nd and age is very limited . therefore , that whether the above - mentioned cessation - age trend is suitable for the rural residents needs to be further explored . in this study , we used fagerstrm test for nicotine dependence ( ftnd ) to assess the degree of nd among rural male current smokers in china and investigated the relationship between nd and age , which will provide evidence needed to better - informed education for tobacco control intervention . smokers : those who have / had smoked 100 or more cigarettes ( or the equivalent amount of tobacco ) during their lifetime . current smokers : those who meet the criterion of smokers , and smoke any tobacco product at the time of the survey . current daily smokers : those who meet the criterion of smokers , and smoke at least once a day at the time of the survey . current occasional smokers : those who meet the criterion of smokers , and smoke but not every day at the time of the survey . ex - smokers : those who meet the criterion of smokers , but do not smoke at all at the time of the survey . this cross - sectional study was conducted from april to may , 2013 , among persons residing in 17 villages of three counties ( pingyin , junan , and liangshan ) in shandong , china . male persons aged 18 years or more and ever spontaneous quitted smoking was face - to - face interviewed by the well - trained investigators to complete a questionnaire that was designed based on the global adult tobacco survey ( gats ) core questionnaire with optional questions . the total amount of valid questionnaires was 1429 , among which , 596 were for current smokers ( including 509 for current daily smokers and 87 for current occasional smokers ) and 833 were for ex - smokers . in this analysis , this study was approved by the ethics review committee of shandong university and all subjects provided informed consent . participants level of nd was assessed using the fagerstrm test for nicotine dependence ( ftnd ) scale ( 14 ) , which measured both physical and psychological tobacco dependence ( 15 ) . the total scores range from 0 to 10 , with higher scores showing greater dependence . the total scale showed good internal consistency reliability in this study ( cronbach s alpha=0.689 ) . the frequency and percent of categorical variables , as well as the mean and standard deviation of metric variables were calculated to describe the demographic characteristics of participants . if the variance between groups was homogeneous , one - way analysis of variance was used to test the difference of means of metric variables between groups ; otherwise , the kruskal - wallis equality - of - populations rank test was used . the adjusted means of the analyzed independent variables were calculated at the means of the other covariates . the association of ftnd scores with age was analyzed using univariate two - degree fractional polynomials ( fps ) regression model , whose best power was chosen from candidates : 2 , 1 , 0.5 , 0 , 0.5 , 1 , 2 , 3 ( 16 , 17 ) . all statistical analyses were carried out using stata version 13.1 ( stata corporation , college station , tx , usa ) . all reported probabilities ( p - value ) were two - sided , and that less than 0.05 were considered statistically significant . smokers : those who have / had smoked 100 or more cigarettes ( or the equivalent amount of tobacco ) during their lifetime . current smokers : those who meet the criterion of smokers , and smoke any tobacco product at the time of the survey . current daily smokers : those who meet the criterion of smokers , and smoke at least once a day at the time of the survey . current occasional smokers : those who meet the criterion of smokers , and smoke but not every day at the time of the survey . ex - smokers : those who meet the criterion of smokers , but do not smoke at all at the time of the survey . this cross - sectional study was conducted from april to may , 2013 , among persons residing in 17 villages of three counties ( pingyin , junan , and liangshan ) in shandong , china . male persons aged 18 years or more and ever spontaneous quitted smoking was face - to - face interviewed by the well - trained investigators to complete a questionnaire that was designed based on the global adult tobacco survey ( gats ) core questionnaire with optional questions . the total amount of valid questionnaires was 1429 , among which , 596 were for current smokers ( including 509 for current daily smokers and 87 for current occasional smokers ) and 833 were for ex - smokers . in this analysis , this study was approved by the ethics review committee of shandong university and all subjects provided informed consent . participants level of nd was assessed using the fagerstrm test for nicotine dependence ( ftnd ) scale ( 14 ) , which measured both physical and psychological tobacco dependence ( 15 ) . the total scores range from 0 to 10 , with higher scores showing greater dependence . the total scale showed good internal consistency reliability in this study ( cronbach s alpha=0.689 ) . the frequency and percent of categorical variables , as well as the mean and standard deviation of metric variables were calculated to describe the demographic characteristics of participants . if the variance between groups was homogeneous , one - way analysis of variance was used to test the difference of means of metric variables between groups ; otherwise , the kruskal - wallis equality - of - populations rank test was used . the adjusted means of the analyzed independent variables were calculated at the means of the other covariates . the association of ftnd scores with age was analyzed using univariate two - degree fractional polynomials ( fps ) regression model , whose best power was chosen from candidates : 2 , 1 , 0.5 , 0 , 0.5 , 1 , 2 , 3 ( 16 , 17 ) . all statistical analyses were carried out using stata version 13.1 ( stata corporation , college station , tx , usa ) . all reported probabilities ( p - value ) were two - sided , and that less than 0.05 were considered statistically significant . the age of subjects ranged from 23 to 80 years old , with an average of 55.08 years . totally , 444 ( 74.50% ) participants were engaged in farming work . overall , 378 ( 63.42% ) participants had a middle level of education ( primary and middle school ) . the characteristics of the subjects note : values are expressed as mean  sd or frequency ( % ) . age group : young = age < 45 , middle=45age < 65 , old = age65 . education : low = below primary school , middle = primary and middle school , high= high school or more . cpd : cigarettes per day . pack - year = cpd/20 number of years smoked the ftnd scores in different age groups ( the mean  sd in < 45 , 4564 , and 65 years of age were 2.522  2.429 , 3.281  2.663 , and 2.963  2.472 , respectively ) analyzed using one - way analysis of variance were significant ( p=0.021 ) with the biggest in 4564 age group . multiple linear regression , with ftnd score as dependent variable , age as independent variable , and potential confounders including categorical variables of occupation , marital status , educational level and metric variables of tertiles of smoking duration and age of smoking onset as the covariates , showed that the adjusted ftnd scores in different age groups ( the adjusted mean  se in < 45 , 4564 , and 65 years of age were 3.033  0.317 , 3.257  0.138 , and 2.592  0.284 , respectively ) were no longer significant ( p=0.068 ) , but the distributional trend of the ftnd scores in different age groups was just similar to that before the adjustment . we used univariate two - degree fps regression to explore the relation of nd to age . the best fps model was that with the powers of 0.5 and 1 , which showed an inverse u - shaped association of nd with age . after adjusting for the above - mentioned potential confounders , the results were not altered significantly ( table 2 & fig . the relation of ftnd score to age estimated by fps with powers of 0.5 and 1 notes : ftnd : score for fagerstrm test of nicotine dependence ; fps : fractional polynomials regression ; education : middle = primary and middle school , high = high school or more . the adjusted curve of relation of ftnd score to age estimated by the univariate two - degree fractional polynomials regression with the best - fit powers ( 0.5 , 1 ) . adjusting for occupation , marital status , education , smoking duration , and age of smoking onset 
 in our study , we also analyzed the effects of age on cigarettes per day ( cpd ) and pack - year . results were just similar to the relationship between nd and age ( data not show ) . the age of subjects ranged from 23 to 80 years old , with an average of 55.08 years . totally , 444 ( 74.50% ) participants were engaged in farming work . overall , 378 ( 63.42% ) participants had a middle level of education ( primary and middle school ) . the characteristics of the subjects note : values are expressed as mean  sd or frequency ( % ) . age group : young = age < 45 , middle=45age < 65 , old = age65 . education : low = below primary school , middle = primary and middle school , high= high school or more . the ftnd scores in different age groups ( the mean  sd in < 45 , 4564 , and 65 years of age were 2.522  2.429 , 3.281  2.663 , and 2.963  2.472 , respectively ) analyzed using one - way analysis of variance were significant ( p=0.021 ) with the biggest in 4564 age group . multiple linear regression , with ftnd score as dependent variable , age as independent variable , and potential confounders including categorical variables of occupation , marital status , educational level and metric variables of tertiles of smoking duration and age of smoking onset as the covariates , showed that the adjusted ftnd scores in different age groups ( the adjusted mean  se in < 45 , 4564 , and 65 years of age were 3.033  0.317 , 3.257  0.138 , and 2.592  0.284 , respectively ) were no longer significant ( p=0.068 ) , but the distributional trend of the ftnd scores in different age groups was just similar to that before the adjustment . we used univariate two - degree fps regression to explore the relation of nd to age . the best fps model was that with the powers of 0.5 and 1 , which showed an inverse u - shaped association of nd with age . after adjusting for the above - mentioned potential confounders , the results were not altered significantly ( table 2 & fig . the relation of ftnd score to age estimated by fps with powers of 0.5 and 1 notes : ftnd : score for fagerstrm test of nicotine dependence ; fps : fractional polynomials regression ; education : middle = primary and middle school , high = high school or more . the adjusted curve of relation of ftnd score to age estimated by the univariate two - degree fractional polynomials regression with the best - fit powers ( 0.5 , 1 ) . ci : confidence interval . adjusting for occupation , marital status , education , smoking duration , and age of smoking onset 
 in our study , we also analyzed the effects of age on cigarettes per day ( cpd ) and pack - year . results were just similar to the relationship between nd and age ( data not show ) . our study indicated that nd level in the middle aged chinese rural current smokers was significantly higher than that in the younger and the older , which showed an inverse u - shaped association . this is consistent with the previous studies conducted in the urban population ( 8 , 9 ) . the definite mechanism of the aforementioned relationship between nd and age is not fully understood . data demonstrate that the availability of the central nicotinic cholinergic receptor could decline significantly with age ( 18 , 19 ) . desensitization of nicotinic cholinergic receptors due to the long time exposure to nicotine will result in the onset of the symptoms of craving or withdrawal of smoking ( 2 ) . therefore , in order to alleviate the craving or avoid torturous withdrawal symptoms , smokers have to use more and more tobacco products to maintain the comparatively high level of plasma nicotine and the sufficient binding ratio of nicotinic receptors , which will aggravate continuously the severity of dependence ( 20 ) . in addition , middle - aged smokers are facing more smoking - related cues from their surroundings than other age groups , such as specific moods ( delighted or depressed emotion , enormous pressures of life and work ) , initiation of social interaction , situations ( working with colleagues , dining together , drinking , driving or being with smoking friends ) , etc . furthermore , comparing with the middle - aged group , younger smokers ( < 45 years ) have higher perceived self - efficacy for quitting and older smokers are less likely to be reactive to psychological cues for the desire to smoke ( 24 , 25 ) . there may be also a variety of factors associated with the descending tendency of nd among the older smokers . firstly , total clearance of nicotine is decreased by 23% , and renal clearance decreased by 49% in the elderly ( age>65 years ) compared to young adults ( 26 ) . as the speed of delivering nicotine to the brain is slow in elderly , lower nicotine metabolism contributes to reduce their urge to smoke , which resulted in decreasing tobacco consumption and the level of nd ( 2 , 26 ) . secondly , owing to the age - related decline in physical function , illness or fear of being ill make the older smokers be more careful about their physical conditions than other age groups ( 21 ) . they , especially those who are suffering from some serious smoking - caused diseases , may spontaneously reduce their daily intake of nicotine from cigarettes and attempt to quit smoking ( 2729 ) . finally , the descending tendency appears due to the survivorship bias brought by the higher death rate among heavier smokers . smokers with higher nd level have an increased susceptibility to dying at younger age than lighter or non - smokers ( 30 , 31 ) . all smoking - induced excess mortality increases with age ( 32 ) , thus resulting probably in leaving individuals with lower nd in the older group . secondly , since nd has a complex etiology generated by many factors , other uninvestigated potential confounders may alter the results . finally , this was only a cross - sectional study , some biases , e.g. selected and recalls bias , might exist and could distort the results . the middle - aged current smokers had higher degree of nd than the younger and the older groups , which showed an inverse u - shaped relationship between nd and age . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .
background : a recent study indicates that the incidence of smoking cessation varies with age . 
 although nicotine dependence ( nd ) has been regarded as one of the most significant barriers of successful smoking cessation , few researches have focused on the relationship between nicotine dependence and age.methods:a cross - sectional study ( conducted in 2013 ) with 596 chinese rural male current smokers was performed to study the relationship between nd and age . 
 the nd level was assessed using the fagerstrm test for nicotine dependence ( ftnd ) scale . 
 the univariate two - degree fractional polynomials ( fps ) regression was used to explore the relation of nd to age.results:the mean of ftnd scores in the middle - aged group ( 4564 yr old ) was higher than that in the younger ( < 45 yr old ) and older groups ( 65 yr old ) . 
 the fps regression showed an inverse u - shaped relationship between nd and age.conclusion:the middle - aged current smokers had higher degree of nd than the younger and the older groups , which showed an inverse u - shaped relationship between nd and age . 
 this finding needs to be confirmed by further researches .