dementia is a clinical syndrome characterized by  a global deterioration of mental functioning in its cognitive , emotional , and cognitive aspects . 
dementia typically involves a long period of progressive decline in memory and other cognitive abilities secondary to brain dysfunction and is a major cause of disability in elderly people .
alzheimer disease is the most common dementing disorder , followed by vascular dementia , frontal lobe dementia , and dementia with lewy bodies .
an expert panel estimated that the global prevalence of dementia is 3.9% in people over 60 years of age , and the estimated global annual incidence of dementia is approximately 7.5 per 1000 people .
the incidence of dementia ranges from approximately 1 per 100 person - years in people aged 60 to 64 years to > 70 per 1000 person - years in people older than 90 years .
because of an increased life expectancy in modern years , the number of people suffering from dementia has rapidly increased , potentially reaching up to 63 million people by 2030 .
the risk factors for dementia include an apolipoprotein e4 genotype , cardiovascular comorbidities , diabetes mellitus , cerebrovascular diseases , alcohol consumption , and a lower education level .
benzodiazepine ( bzd ) and other non - selective -aminobutyric acid ( gaba ) agonists with hypnotic effects similar to those of zolpidem have been shown to disrupt the memory in both human participants and animal subjects .
the results of previous studies have suggested that bzds are associated with an increased risk of dementia in the elderly population , and these risks decreased when bzd use is discontinued .
however , the possibility that zolpidem used independently of benzodiazepine derivatives , increases the risk for dementia has not been proposed .
zolpidem and its derivatives ( the z drugs ) are non - bzd hypnotic agent belonging to the imidazopyridine family .
zolpidem acts as an agonist of the benzodiazepine 1 receptor component of the gabaa receptor complex and is commonly used in patients with insomnia , including elderly patients .
zolpidem is well known for having a rapid onset ( usually several minutes ) , short duration of action ( the peak time is 2 hours , half time is 1.55.5 hours ) , low tolerance , and a low incidence of adverse effects in treating insomnia .
the most frequent adverse effects associated with zolpidem are nausea , headache , dizziness , drowsiness , hallucination , and short - term memory loss .
a 3-week clinical trial revealed psychomotor retardation in 2% of patients receiving zolpidem and in 0% of patients in the placebo group .
however , there are limited clinical data concerning the effects of long - term zolpidem use on psychomotor or cognitive functions .
thus , the relationship between the use of zolpidem and the potential risk of developing dementia remains unknown . in the present study
, we used a national population data bank to explore the associations between zolpidem and all dementia , non - alzheimer disease dementia , and alzheimer disease .
a case  control study was conducted using data from the taiwan national health insurance research database ( nhird ) .
the taiwan national health insurance research database ( nhird ) contains reimbursement claims data from the taiwan national health insurance ( nhi ) system , which was established in 1996 and has provided coverage for approximately 99% of the population since 1998 .
the national health research institute ( nhri ) manages the annual claims data in the nhird , and the longitudinal health insurance database ( lhid ) was established for use in medical research .
the demographic data , medications , treatments ( including operations ) , and disease diagnoses ( based on the international classification of diseases , ninth revision , clinical modification [ icd-9-cm ] ) of patients are recorded in the nhird . the health facilities enrolled in the taiwan nhi include local clinics , community hospitals , regional hospitals , and medical centers . with the exception of some local clinics ,
the taiwanese nhi includes almost all the primary , secondary , tertiary , and quaternary health care facilities in taiwan .
the lhid comprises historical claims data for 1 million patients randomly selected from the nhird .
the nhri encrypts the patients personal information for privacy protection and provides researchers with anonymous identification numbers associated with the relevant claim information , which includes the patient 's sex , date of birth , registry of medical services , and medication prescriptions .
this study was approved by the institutional review board of china medical university in central taiwan ( cmu - rec-101012 ) . a population - based case 
patients 65 years and older diagnosed with dementia ( icd-9-cm 290 , 294 ) and alzheimer disease ( 331.0 ) in 2006 to 2010 were defined as a case group .
the patients with the diagnosis with alzheimer disease were diagnosed by the board - certified neurologists and meet the following criteria : did not have history of severe trauma , stroke , or other neurology diseases that might interfere with the cognitive functions ; have decreased score in mini - mental state examination and cognitive ability screening instrument , complete blood sampling studies , and imaging studies .
the control group was selected from the people without dementia diagnosis in lhid observation and was 2-fold frequency matched according to sex , age ( per 5 years ) , and index year .
if the patients ever used zolpidem before index date , they were grouped into zolpidem used group .
however , patients without zolpidem used before index date classified into non - zolpidem used group .
the average zolpidem exposure dose was calculated by dividing the total zolpidem exposure ( milligrams ) according to the period between the first exposure and the index date ( years ) .
other dementia - associated comorbidities were also considered potential confounding factors to determine associations between dementia and zolpidem .
data for the underlying comorbidities , including hypertension ( icd-9-cm 401405 ) , diabetes ( icd-9-cm 250 ) , coronary artery disease ( cad ) ( icd-9-cm 410414 ) , stroke ( icd-9-cm 430438 ) , hyperlipidemia ( icd-9-cm 272 ) , depression ( icd-9-cm 296.2296.3 and 300.4 ) , and anxiety ( icd-9-cm 300.0 , 300.2 , 300.3 , 308.3 , and 309.81 ) , were collected before the index date .
drugs potentially associated with the development of dementia , including anti - hypertension agents such as calcium channel blockers ( anatomical therapeutic chemical [ atc ] code : c08 ) , beta - blockers ( atc code : c07 ) , alpha - blockers ( atc code : c02 ) , diuretics ( atc code : c03 ) , angiotensin - converting enzyme antagonists ( acei ) , angiotensin receptor blockers ( arb ) ( atc code : c09 ) , and anticholesterol statin drugs ( atc code : c10 ) benzodiazepine ( atc code : n05 ) , and similar derivative drugs that were available such as zopiclone ( atc code : n05 ) were analyzed .
we also considered effect of anti - psychotic drug used ( first generation antipsychotics and second generation antipsychotics ) and anti - depression drug used ( including selective serotonin reuptake inhibitors , monoamine oxidase inhibitors , heterocyclic antidepressants , and others [ bupropion , venlafaxine , mirtazapine , and duloxetine ] ) . all of these drug definitions were considered the drug use group as the patients at least once use before the index date .
the distribution of the study population , which was based on the demographic characteristics and the disease history data , was analyzed .
the  test was used for categorical variables , and student t test was used for continuous variables to evaluate the differences among the study groups .
the odds ratio ( or ) and 95% confidence interval ( 95% ci ) were measured for each comparison to estimate the associations between zolpidem use and dementia using logistic regression .
adjusted odds ratios ( aors ) were also determined after adjusting for potential confounders . to evaluate the dose response of the association between the average zolpidem dose and dementia ,
logistic regression was used , and the average zolpidem dose was treated as a continuous variable across a range of average doses to evaluate trends in dementia diagnosis .
we tested the multiplicative interaction of zolpidem use and each comorbidities ( or drugs ) by logistic regression and presented the effect of zolpidem for dementia under the different level of each comorbidities ( or drugs ) .
all data management and statistical analyses were performed using the sas 9.1.3 software ( sas institute , cary , nc ) .
all statistical tests were 2-sided , and p values < 0.05 were considered statistically significant .
a case  control study was conducted using data from the taiwan national health insurance research database ( nhird ) .
the taiwan national health insurance research database ( nhird ) contains reimbursement claims data from the taiwan national health insurance ( nhi ) system , which was established in 1996 and has provided coverage for approximately 99% of the population since 1998 .
the national health research institute ( nhri ) manages the annual claims data in the nhird , and the longitudinal health insurance database ( lhid ) was established for use in medical research .
the demographic data , medications , treatments ( including operations ) , and disease diagnoses ( based on the international classification of diseases , ninth revision , clinical modification [ icd-9-cm ] ) of patients are recorded in the nhird . the health facilities enrolled in the taiwan nhi include local clinics , community hospitals , regional hospitals , and medical centers . with the exception of some local clinics ,
the taiwanese nhi includes almost all the primary , secondary , tertiary , and quaternary health care facilities in taiwan .
the lhid comprises historical claims data for 1 million patients randomly selected from the nhird .
the nhri encrypts the patients personal information for privacy protection and provides researchers with anonymous identification numbers associated with the relevant claim information , which includes the patient 's sex , date of birth , registry of medical services , and medication prescriptions .
this study was approved by the institutional review board of china medical university in central taiwan ( cmu - rec-101012 ) .
patients 65 years and older diagnosed with dementia ( icd-9-cm 290 , 294 ) and alzheimer disease ( 331.0 ) in 2006 to 2010 were defined as a case group .
the patients with the diagnosis with alzheimer disease were diagnosed by the board - certified neurologists and meet the following criteria : did not have history of severe trauma , stroke , or other neurology diseases that might interfere with the cognitive functions ; have decreased score in mini - mental state examination and cognitive ability screening instrument , complete blood sampling studies , and imaging studies .
the control group was selected from the people without dementia diagnosis in lhid observation and was 2-fold frequency matched according to sex , age ( per 5 years ) , and index year .
if the patients ever used zolpidem before index date , they were grouped into zolpidem used group .
however , patients without zolpidem used before index date classified into non - zolpidem used group .
the average zolpidem exposure dose was calculated by dividing the total zolpidem exposure ( milligrams ) according to the period between the first exposure and the index date ( years ) .
other dementia - associated comorbidities were also considered potential confounding factors to determine associations between dementia and zolpidem .
data for the underlying comorbidities , including hypertension ( icd-9-cm 401405 ) , diabetes ( icd-9-cm 250 ) , coronary artery disease ( cad ) ( icd-9-cm 410414 ) , stroke ( icd-9-cm 430438 ) , hyperlipidemia ( icd-9-cm 272 ) , depression ( icd-9-cm 296.2296.3 and 300.4 ) , and anxiety ( icd-9-cm 300.0 , 300.2 , 300.3 , 308.3 , and 309.81 ) , were collected before the index date .
drugs potentially associated with the development of dementia , including anti - hypertension agents such as calcium channel blockers ( anatomical therapeutic chemical [ atc ] code : c08 ) , beta - blockers ( atc code : c07 ) , alpha - blockers ( atc code : c02 ) , diuretics ( atc code : c03 ) , angiotensin - converting enzyme antagonists ( acei ) , angiotensin receptor blockers ( arb ) ( atc code : c09 ) , and anticholesterol statin drugs ( atc code : c10 ) benzodiazepine ( atc code : n05 ) , and similar derivative drugs that were available such as zopiclone ( atc code : n05 ) were analyzed .
we also considered effect of anti - psychotic drug used ( first generation antipsychotics and second generation antipsychotics ) and anti - depression drug used ( including selective serotonin reuptake inhibitors , monoamine oxidase inhibitors , heterocyclic antidepressants , and others [ bupropion , venlafaxine , mirtazapine , and duloxetine ] ) .
all of these drug definitions were considered the drug use group as the patients at least once use before the index date .
the distribution of the study population , which was based on the demographic characteristics and the disease history data , was analyzed .
the  test was used for categorical variables , and student t test was used for continuous variables to evaluate the differences among the study groups .
the odds ratio ( or ) and 95% confidence interval ( 95% ci ) were measured for each comparison to estimate the associations between zolpidem use and dementia using logistic regression .
adjusted odds ratios ( aors ) were also determined after adjusting for potential confounders . to evaluate the dose response of the association between the average zolpidem dose and dementia ,
logistic regression was used , and the average zolpidem dose was treated as a continuous variable across a range of average doses to evaluate trends in dementia diagnosis .
we tested the multiplicative interaction of zolpidem use and each comorbidities ( or drugs ) by logistic regression and presented the effect of zolpidem for dementia under the different level of each comorbidities ( or drugs ) .
all data management and statistical analyses were performed using the sas 9.1.3 software ( sas institute , cary , nc ) .
all statistical tests were 2-sided , and p values < 0.05 were considered statistically significant .
a total of 8406 dementia patient files were identified , and the control group consisted of 16,812 patients .
the demographic characteristics of the study population are presented in table 1 . comparing with the control group , the dementia patients have longer zolpidem exposure time ( 302.8 days vs 345.1 days , p  =  0.001 ) and higher exposure dose , were more likely to have been exposed to zolpidem ( 44.8% vs 30% , p  <  0.0001 ) , zopiclone ( 20.3% vs 12.9% , p  <  0.0001 ) , and bzds ( 91.3% vs 83.6% , p  <  0.0001 ) , to have received simultaneous treatments with anti - hypertension agents ( 79.8% vs 70.3% , p  <  0.0001 ) and anti - cholesterol statin agents ( 26.3% vs 22% , p  <  0.0001 ) , and to have had underlying diseases , such as hypertension ( 81.6% vs 72.6% , p  <  0.0001 ) , diabetes ( 32.2% vs 24.1% , p  <  0.0001 ) , stroke ( 28.3% vs 12.2% , p  <  0.0001 ) , cad ( 51% vs 42% , p  <  0.0001 ) , hyperlipidemia ( 41.2% vs 36% , p  <  0.0001 ) , depression ( 17.1% vs 6.3% , p 
<  0.0001 ) , and anxiety disorder ( 27.4% vs 17.9% , p  <  0.0001 ) .
demographic status and comorbidity compared between control group and dementia group the logistic regression models were adjusted for potential confounders , such as age , sex , cad , diabetes , stroke , hyperlipidemia , depression , anxiety , and the use of antihypertension agents , anticholesterol statin agents zopiclone and bzd drug uses , to evaluate the relationship between zolpidem use and dementia ( table 2 ) .
zolpidem use and dementia remained significantly associated ( dementia : aor  =  1.33 , 95% ci 1.241.41 ; p  < 
0.0001 ; non - alzheimer disease dementia : aor  =  1.33 , 95% ci 1.251.42 ; p  <  0.0001 ) , although the relationship effects between the zolpidem use and alzheimer disease were not significant ( alzheimer disease : aor  =  1.17 , 95% ci 0.901.54 , p  =  0.2410 ) .
effects of zolpidem exposure on dementia in individuals in different average cumulative exposure doses the average cumulative zolpidem doses were analyzed to identify dose effects .
response effects for most of types of dementia except alzheimer disease ( dementia : < 170  mg / y [ aor  =  1.18 , 95% ci 1.111.28 ] , 170819  mg / y [ aor  =  1.50 , 95% ci 1.361.65 ] , 820  mg / y [ aor  =  1.52 , 95% ci 1.381.68 ] , p value for trend < 0.001 ; non - alzheimer disease dementia : < 170  mg / y [ aor  =  1.20 , 95% ci 1.111.29 ] , 170819  mg / y [ aor  =  1.49 , 95% ci 1.341.65 ] , 820  mg / y [ aor  =  1.55 , 95% ci 1.391.72 ] , p value for trend < 0.001 ; and alzheimer disease : < 170  mg / y [ aor  =  0.97 , 95% ci 0.681.37 ] , 170819  mg / y [ aor  =  1.65 , 95% ci 1.082.51 ] , 820  mg / y [ aor  =  1.15 , 95% ci 0.781.78 ] , p value for trend  =  0.4413 ) .
potential modifying effects for comorbidities that might interfere with the association between dementia and zolpidem were analyzed ( table 3 ) .
although effect modifiers such as hypertension , diabetes , stroke , cad , hyperlipidemia , and anxiety , depression , anti - psychotic agent , and anti - depressant use had positive effects for dementia ( hypertension : aor  =  1.72 , 95% ci 1.621.83 ; diabetes : aor  =  1.64 , 95% ci 1.481.81 ; stroke : aor  =  1.39 , 95% ci 1.231.57 ; cad : aor  =  1.74 , 95% ci 1.611.88 ; hyperlipidemia : aor  =  1.74 , 95% ci 1.601.90 ; anxiety : aor  =  1.66 , 95% ci 1.481.86 ; depression : aor  =  1.37 , 95% ci 1.151.63 ) , zolpidem exposure alone also has more positive effects on dementia in most circumstances ( non - hypertension : aor  =  2.30 , 95% ci 2.012.62 ; non - diabetes : aor  =  1.95 , 95% ci 1.832.08 ; non - stroke : aor  =  1.88 , 95% ci 1.762.00 ; non - cad : aor  =  1.88 , 95% ci 1.762.00 ; non - hyperlipidemia : aor  =  1.95 , 95% ci 1.822.10 ; non - statin : aor  =  1.92 , 95% ci 1.802.04 ; non - bzd : aor  =  1.96 , 95% ci 1.492.59 ; non - anxiety : aor  =  1.76 , 95% ci 1.651.88 ; non - depression : aor  =  1.68 , 95% ci 1.581.78 ) .
patients receiving zolpidem with anti - psychotic or anti - depressant agents at the same time had more positive effects on dementia risk ( anti - psychotic agents vs non - antipsychotic agents : aor  =  1.75 [ 95% ci 1.611.90 ] vs. 1.57 [ 95% ci 1.461.70 ] ; anti - depressant vs non - antidepressant agents : aor  =  1.66 [ 95% ci 1.541.80 ] vs 1.54 [ 95% ci 1.421.68 ] ) . although large numbers of patients were co - prescribed zolpidem and bzd derivatives , the effects of interactions between zolpidem and bzd derivatives were not significant .
control study suggests that zolpidem use might increase the risk of developing dementia in the elderly population .
the accumulative dose of zolpidem , alone , or with other underlying diseases , such as hypertension , diabetes , and stroke , was significantly associated with dementia after controlling for potential confounders , such as age , sex , cad , diabetes , antihypertension drugs , stroke , anticholesterol statin drugs , depression , anxiety , and bzd use ; however , the effects of zolpidem on patients with alzheimer disease remained obscure .
the adjusted odds ratio for patients whose cumulative exposure doses were between 170 and 819  mg / year ( adjusted or : 1.65 , 95% ci 1.082.51 , p 
=  0.0199 ) was significant ; however , the effects for lower and higher cumulative dose were not significant .
alzheimer disease is the leading subtype of dementia and has been identified as a protein degenerative disease that is primarily caused by the accumulation of abnormally folded amyloid beta and phosphorylated tau proteins in the brain .
clinical presentations , histories , neurological examinations , images , and biomarkers are required to diagnose alzheimer disease .
dementias other than alzheimer disease ( non - alzheimer dementias ) comprise heterogeneous diseases , including vascular dementia , mixed dementia , parkinson disease , dementia with lewy bodies , huntington disease , creutzfeldt  jakob disease , and frontotemporal dementia / pick disease . interactions between other factors , such as hypercholesterolemia , hypertension , atherosclerosis , coronary heart disease , smoking , obesity , diabetes , and sleep deprivation or sleep fragmentation , were reported to be risk factors that might contribute to dementia .
however , few studies have addressed the potential long - term psychoneurological effects of drugs on non - alzheimer dementia or alzheimer disease .
zolpidem is an effective non - bzd drug that is primarily used for treating insomnia in the elderly population .
previous clinical trials have demonstrated the effects of zolpidem on the central nervous system ( eg , confusion , impaired cognitive and motor function , postural sway , and ataxia ) , and an increased risk of falling has also been observed .
comparable dose - related impairment was also observed in healthy participants asked to perform cognitive - related tests , such as picture recall , digit entry and recall , a digit symbol substitution test , repeated acquisition and circular lights tasks , and balance tests .
the cognition - impairing effects in executive function tasks were characterized in animal models before .
previous study results suggested that zolpidem displays a high affinity for 1 subunit of gabaa receptors ; therefore , the drug impairs the human cognitive domain in the prefrontal cortical areas , which are involved in processes such as goal forming , planning , initiation , preservation and alteration of goal - directed behaviors , problem - solving , response inhibition , and cognitive flexibility .
because the aging brain has increased 1 subunit of gabaa receptor  binding sites and 1 subunit of gabaa receptor mrna levels , the cognition - impairing effects of zolpidem might reflect the elderly population 's increased risk of developing non - alzheimer dementia .
in contrast , the 1 subunit of gabaa receptor protein and mrna levels were reduced in the brain cortex regions of alzheimer disease patients .
the different compositions indicate that increases or decreases in the proportion of receptors containing a particular  subunit may reflect the affinity of the receptor for zolpidem , resulting in altered drug responses between patients of non - alzheimer dementias and alzheimer disease in the elderly population . whether cognitive effects on zolpidem could extend to other z drugs still remain obscure .
previous studies suggested zaleplon had a rapid elimination and had fewer residual side effects after taking a single dose at bedtime . by comparison ,
the differences in potency based on plasma concentrations suggested that there are differences in binding to the gaba receptor complex .
for example , zopiclone interacts with both benzodiazepine 1and 2 gabaa receptors , and zolpidem mainly acts on benzodiazepine 1 gabaa receptors .
therefore , there may be a prolonged drug effect and result in residual sedation and side effects .
the z drugs undergoes hepatic metabolism by cytochrome p450 . the delayed clearances of the z drugs were significantly decreased in patients with preexisting advanced liver diseases .
furthermore , variations in genetic polymorphism of the cytochrome p450 in different population might result in different responses as well .
a study has suggested that the cyp3a4 and cyp2c19 genetic polymorphisms are associated with the poor metabolism of zolpidem in the chinese han population .
a limited number of human studies have explored the relationship between neuropsychological drugs and the development of dementia or alzheimer disease . a meta - analysis setting out to ascertain
which domains of cognitive function were influenced among the z drugs indicated very few studies evaluate the individual cognitive effects of the z drugs .
most of the studies focused on the next - day residual cognitive effects of the z drugs following nocturnal administration .
the z drugs have been heralded as a new frontier with consistent increase in the prescription in the pharmacological treatments available for insomnia patients due to the adverse and deleterious effects associated with long - term benzodiazepine use .
there needs to be more thorough investigations into the possible effects on the daily functioning of individuals who take these medications .
the results of the present study indicate the potential associations regarding the cumulative dose and interactions among commonly prescribed tranquilizers , zolpidem , underlying comorbidities , and the development of dementia or alzheimer disease in the elderly population .
although detailed observations and medical records were not obtained and effect modifiers and confounders were not completely controlled , correlations between zolpidem and dementia in the elderly population were observed .
the limitations of the present study include the limitations of the clinical data collected from the nhird , the difficulty associated with controlling for confounding factors in a retrospective study design , and the incomplete verification of the data in the nhird
. the nhird does not provide detailed information regarding smoking habits , alcohol consumption , substance use , body mass index , physical activity , socioeconomic status , family history , and detailed medical records such as sleep quality records , reasons for zolpidem withdrawal , or intermittent used , which are potential confounding factors for this analysis .
furthermore , some patients in control group might present prodromal symptoms like nxiety , depression , or insomnia before dementia diagnosis was made and led to misclassification and selection bias .
the registries in the nhi claims system were primarily designed for administrative billing , and the registry data are not subjected to the stringent levels of verification appropriate for many types of scientific research .
there was also no method for directly contacting the patients to obtain additional information on the use of zolpidem because the participants remained anonymous .
however , the data from the nhird regarding prescriptions and the diagnosis of major underlying diseases and dementia are highly reliable .
qualified neurologists performed a series of neurological examinations . because of the limitations of the nhird , the prescription records for zolpidem before 1996 were not acquired for analysis ; therefore , shorter follow - up examinations and lower cumulative doses for zolpidem were calculated , and the risk associations between zolpidem and dementia might also be underestimated .
future studies , such as population - based unbiased randomized observational trials , are warranted to confirm the causal relationships between zolpidem use and dementia . in conclusion
, zolpidem use might be associated with an increased risk for dementia in the elderly population .
an increased accumulative dose might result in a significantly higher risk to develop dementia in patients with underlying diseases , such as hypertension , diabetes , and stroke .
the long - term effects of zolpidem on patients with alzheimer disease might not be significant in the elderly population .
therefore , the careful evaluation of the indications of zolpidem use and close follow - up examinations of the cognitive status of elderly patients receiving zolpidem are essential .
 abstractwe evaluate the effects of zolpidem use to develop dementia or alzheimer disease from the taiwan national health insurance research database ( nhird).a retrospective population - based nested case  control study . 
 newly diagnosed dementia patients 65 years and older and controls were sampled . 
 a total of 8406 dementia and 16,812 control subjects were enrolled from taiwan nhird during 2006 to 2010 . 
 the relationships between zolpidem use and dementia were measured using odds and adjusted odds ratios . 
 the relationship between the average cumulative doses for zolpidem and dementia was also analyzed.zolpidem alone or with other underlying diseases , such as hypertension , diabetes , and stroke , was significantly associated with dementia after controlling for potential confounders , such as age , sex , coronary artery disease , diabetes , anti - hypertension drugs , stroke , anticholesterol statin drugs , depression , anxiety , benzodiazepine , anti - psychotic , and anti - depressant agents use ( adjusted or  =  1.33 , 95% ci 1.241.41 ) . 
 zolpidem use also has significant dose  
 response effects for most of the types of dementia . in patient with alzheimer diseases , 
 the effects of zolpidem among patients with alzheimer 's disease remained obscure . 
 the adjusted or for patients whose cumulative exposure doses were between 170 and 819  mg / year ( adjusted or : 1.65 , 95% ci 1.082.51 , p  
 =  0.0199 ) was significant ; however , the effects for lower and higher cumulative dose were not significant.zolpidem used might be associated with increased risk for dementia in elderly population . 
 increased accumulative dose might have higher risk to develop dementia , especially in patients with underlying diseases such as hypertension , diabetes , and stroke . 
INTRODUCTION
MATERIALS AND METHODS
Data Source
Study Design
Statistical Analysis
RESULTS
DISCUSSION
LIMITATIONS