***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: We examined the effects on sleep and memory of a nighttime dose of triazolam , 0.125 mg , in seven subjects with Alzheimer 's disease ( AD ) who were reported by caregivers to be frequently up at night . Subjects were admitted to an intermediate care hospital ward for the 8-day ABA design protocol ( placebo baseline-drug-placebo washout ) . Drug or placebo was given each evening at 2100 h. Sleep was assessed with a wrist-worn activity monitor . Memory was evaluated using a computerized delayed-matching-to- sample ( DMTS ) task administered at 0800 and 2130 h. Triazolam had no significant effects on total sleep time at night , latency to sleep onset , number of arousals , or time asleep during the day . DMTS performance was significantly worse at night compared to morning during baseline , but there were no significant drug effects . Our results suggest the st and ard geriatric dose of triazolam , 0.125 mg , may not be an effective hypnotic in AD patients with disrupted sleep , but neither does it substantially worsen the recent memory deficits of AD Fifty-nine elderly residents of long-term care facilities who had DSM-III diagnoses of dementia were studied in an 8-week r and omized , double-blind comparison trial of haloperidol , oxazepam , and diphenhydramine to test the efficacy of these agents in the treatment of clinical ly significant behavioral disturbances in patients with dementia . All three agents demonstrated modest but significant efficacy as measured by clinician ratings of agitated behavior and activities of daily living . The absolute magnitude of improvement was greater for haloperidol and diphenhydramine than for oxazepam , but differences among groups did not approach statistical significance . Frequencies of acute adverse events during the trial were similar across the drug treatment groups . Although these drugs may differ in terms of long-term safety and efficacy , they appear to be equivalent for short-term management of agitated behavior in severely demented patients Objective To evaluate the association between use of benzodiazepines and incident dementia . Design Prospect i ve , population based study . Setting PAQUID study , France . Participants 1063 men and women ( mean age 78.2 years ) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up . Main outcome measures Incident dementia , confirmed by a neurologist . Results During a 15 year follow-up , 253 incident cases of dementia were confirmed . New use of benzodiazepines was associated with an increased risk of dementia ( multivariable adjusted hazard ratio 1.60 , 95 % confidence interval 1.08 to 2.38 ) . Sensitivity analysis considering the existence of depressive symptoms showed a similar association ( hazard ratio 1.62 , 1.08 to 2.43 ) . A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia . The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 ( 1.10 to 1.94 ) . Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50 % increase in the risk of dementia ( adjusted odds ratio 1.55 , 1.24 to 1.95 ) compared with never users . The results were similar in past users ( odds ratio 1.56 , 1.23 to 1.98 ) and recent users ( 1.48 , 0.83 to 2.63 ) but reached significance only for past users . Conclusions In this prospect i ve population based study , new use of benzodiazepines was associated with increased risk of dementia . The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study . Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population , indiscriminate widespread use should be caution ed against PURPOSE To assess the prevalence of adverse drug reactions ( ADRs ) occurring in patients with Alzheimer 's disease ( AD ) or other dementia in France . METHODS A cross-sectional multicentre study was conducted by the French network of the 31 regional pharmacovigilance centres on a given day . The subjects were selected by r and om draw to be a representative sample of French patients with dementia : consultations of dementia clinics , nursing-homes , acute and long care geriatric units , rehabilitation care geriatric units . The staff of each medical structure together with that of the pharmacovigilance centre defined a day for including the patients . Socio-demographic data , history , ADR and drugs given were registered . RESULTS There were 1332 subjects included , 51.1 % living at home , 48.8 % in institutions , aged 82.0 ± 8.0 years ( 46 - 108 ) ; 61.3 % suffered from  AD . Mean number of drugs was 6.3 ± 3.1 . Anti-dementia drugs were given to 66.4 % subjects . ADR prevalence was 5.0 % ( 95 % CI : 3.9 - 6.2 ) without a significant difference between at home and institutionalized patients . ADR consisted of gastro-intestinal ( 23.2 % ) , central nervous system ( 17.4 % ) and psychiatric disorders ( 8.7 % ) . Of the ADR , 31.9 % were serious , and 47.8 % preventable . The drugs most often involved were anti-dementia ( 28.9 % ) , cardio-vascular ( 28.9 % ) and psychotropic drugs ( 26.4 % , anxiolytics , hypnotics , antidepressants , neuroleptics ) . CONCLUSION This national scale study showed that iatrogenesis in patients with AD and related dementia can at times be serious and preventable . Therefore , special attention is required when prescribing psychotropic and anti-dementia drugs , as they are frequently used and induce half of the ADR in this population BACKGROUND Little is known about the side effects of sedative-hypnotic agents in elderly dementia patients with sleep disorders . The present study describes activity pattern changes after a single dose of brotizolam in elderly patients with dementia . METHODS We conducted retrospective analysis of prospect ively collected data from a case series at Asakayama Hospital ( Osaka , Japan ) between September 2008 and September 2009 . Around-the-clock movements of dementia patients who were administered a single dose of brotizolam were recorded by the integrated circuit tag monitoring system during a 4-week baseline and 7-day peri-administration period .  Diurnal and nocturnal activity levels and the onset times of the least-active and most-active phases were then measured . RESULTS Seven patients ( four men , three women ; age range 59 - 85 years ) were analyzed . All seven patients had disturbed activity patterns during the peri-administration period . Compared with the pre-administration period , the incidence of reversed rest-activity pattern increased significantly in the post-administration period , as measured by the distance moved per hour ( P < 0.000 ) . Patients with advanced stages of dementia had prolonged and delayed activity responses . CONCLUSIONS Findings showed changes in activity levels and reversed active/resting phases after a single dose of brotizolam in elderly patients with dementia . Use of brotizolam in elderly patients with dementia , especially in advanced stages , calls for closer attention and longer observation periods Objective Few studies have investigated  potentially inappropriate medication ( PIM ) use in patients with Alzheimer ’s disease ( AD ) . The aim of our study was to assess the prevalence of PIM  in community-dwelling patients diagnosed with mild-to-moderate AD and identify the clinical factors associated with PIM prescriptions . Methods REAL.FR is a 4-year , prospect i ve , multicenter French cohort of AD patients recruited in centers of expertise . We analyzed patient baseline data at entry into the study .  PIMs  were assessed using the Laroche list . A  multivariate logistic regression was conducted to assess factors associated with PIMs . Results A total of 684 AD patients were enrolled in the study [ mean age 77.9 ± 6.8 years , 486 ( 71.0 % ) females ] . According to the Laroche list , 46.8 % [ 95 % confidence interval ( CI ) 43.0–50.5 % ] of the patients had at least one  PIM . “ Cerebral vasodilators ” were the most widely used class of PIM , accounting for 24.0 % ( 95 % CI 20.9–27.3 % ) of all prescriptions , followed by atropinic drugs ( 17.0 % , 95 % CI 14.1–19.8 % ) and long half-life benzodiazepines ( 8.5 % , 95 % CI 6.4–10.6 % ) . Atropinic drugs were associated with cholinesterase inhibitors in 16 % of patients . In the multivariate analysis , only two factors , namely , female gender [ odds ratio ( OR ) 1.5 , 95 % CI 1.1–2.2 ] and polypharmacy ( ≥5 drugs ; OR 3.6 , 95 % CI 2.6–4.5 ) were associated with prescriptions for PIMs . Conclusions These results reveal that approximately one out of two community-dwelling patients with mild-to-moderate AD treated by AD specialists use PIMs . They also indicate that the characteristics of the disease and the pharmacodynamic/pharmacokinetic profile of the drugs prescribed are not sufficiently taken into account by physicians when prescribing for AD patients Unbound plasma concentrations of diazepam and flunitrazepam were related to psychomotor and subjective effects of the two drugs . The interindividual variability in plasma protein binding of both diazepam ( 98.5 ± 0.14 % ) and flunitrazepam ( 84.5 ± 1.2 % ) was relatively small , and high correlations were therefore observed between the individual unbound and total drug plasma concentrations after a particular dose . However , poor correlations were seen between individual unbound drug plasma concentrations and psychomotor or subjective effects . This observation indicates that factors other than individual variability in drug plasma concentration , account for the pronounced individual differences in , for example , psychomotor impairment frequently observed after intake of benzodiazepines . Furthermore , based on a linear relationship between unbound drug plasma concentrations and increase in either complex choice or simple reaction time , the potency of flunitrazepam was calculated to be about seven times higher than the potency of diazepam . This is approximately two times higher than expected from the reported in vitro affinity of the two drugs for the benzodiazepine receptor . This finding may indicate that flunitrazepam may have a higher apparent in vivo intrinsic efficacy than diazepam when assessed by psychomotor impairment This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer 's disease and /or vascular dementia . At 2 h , olanzapine ( 5.0 mg , 2.5 mg ) and lorazepam ( 1.0 mg ) showed significant improvement over placebo on the PANSS Excited Component ( PANSS-EC ) and Agitation – Calmness Evaluation Scale ( ACES ) , and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory . At 24 h , both olanzapine groups maintained superiority over placebo on the PANSS-EC ;  lorazepam did not . Olanzapine ( 5.0 mg ) and lorazepam  improved ACES scores more than placebo . Simpson – Angus and Mini-Mental State Examination scores did not change significantly from baseline . Sedation ( ACES ⩾8 ) , adverse events , and laboratory analytes were not significantly different from placebo for any treatment . No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h , and no significant differences among treatment groups were seen in vital signs , including orthostasis . Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating in patients with acute dementia-related agitation The objective of this study was to estimate the prevalence of antipsychotic use and investigate their association with behavioural and psychological symptoms of dementia ( BPSD ) and other clinical predictors . Patients with dementia , aged 65 and above and resident in 35 Alzheimer special care units were sequentially enrolled into a 18-month prospect i ve observational study . Data on sociodemographic , cognitive , functional , behavioural and clinical characteristics and drug exposure were collected at baseline and at 6-month intervals up to 18 months . The prevalence of antipsychotic use and the association with BPSD and clinical predictors were analysed . Of the 349 patients with dementia enrolled in the study , 209 ( 60 % ) were taking at least one antipsychotic . Risperidone and promazine were the most frequently prescribed antipsychotic ; 40.7 % simultaneously received a benzodiazepine , 20 % an antidepressant . More than 50 % were still taking antipsychotics at 18 months of follow-up . No associations were found between  antipsychotic use and level of cognitive impairment , basal activity of daily living disability and comorbidity . Multivariate analysis showed that 
    Output:
    
Conclusion : This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer ’s disease patients .