human
***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: OBJECTIVES To investigate the effects of darifenacin controlled-release ( CR ) and oxybutynin extended-release ( ER ) on cognitive function ( particularly memory ) in older subjects . METHODS Healthy subjects ( n=150 ) > /=60 years were r and omised to darifenacin , oxybutynin ER or placebo in a multicentre , double-blind , double-dummy , parallel-group , 3-week study . Doses were administered according to US labels : oxybutynin ER 10 mg once daily ( od ) , increasing to 15 mg od then 20 mg od by week 3 ; darifenacin 7.5 mg od in weeks 1 and 2 , then 15 mg od in week 3 . The primary end point was accuracy on the Name-Face Association Test ( delayed recall ) at week 3 . RESULTS Results of the Name-Face Association Test at week 3 showed no significant difference between darifenacin and placebo on delayed recall ( mean difference , -0.06 , p=0.908 ) . In contrast , oxybutynin ER result ed in memory impairment , with significantly lower scores than placebo and darifenacin ( mean differences , -1.30 , p=0.011 and -1.24 , p=0.022 , respectively ) for delayed recall on the Name-Face Association Test at week 3 . Additional tests of delayed recall indicated significant memory impairment with oxybutynin ER versus placebo at certain time points , whereas darifenacin was similar to placebo . No between-treatment differences were detected in self-rated memory , demonstrating that subjects were unaware of memory deterioration . CONCLUSIONS While darifenacin had no significant effects on memory versus placebo , oxybutynin ER caused significant memory deterioration ( magnitude of effect comparable to brain aging of 10 years ) . The results also demonstrate that subjects may not recognise/report memory deterioration INTRODUCTION Anti-cholinergic medications have been associated with increased risks of cognitive impairment , premature mortality and increased risk of hospitalisation . Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer , yet little is known about associated adverse outcomes in this setting . METHODS A sub study of 112 participants in a r and omised control trial who had cancer and an Australia modified Karnofsky Performance Scale ( AKPS ) score ( AKPS ) of 60 or above , explored survival and health service utilisation ; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale ( modified version ) longitudinally to death . A st and ardised starting point for prospect ively calculating survival was an AKPS of 60 or above . RESULTS Baseline entry to the sub- study was a mean 62 + /- 81 days ( median 37 , range 1 - 588 ) days before death ( survival ) , with mean of 4.8 ( median 3 , SD 4.18 , range 1 - 24 ) study assessment s in this time period . Participants spent 22 % of time as an inpatient . There was no significant association between anti-cholinergic score and time spent as an inpatient ( adjusted for survival time ) ( p = 0.94 ) ; or survival time . DISCUSSION No association between anti-cholinergic load and survival or time spent as an inpatient was seen . Future studies need to include cognitively impaired population s where the risks of symptomatic deterioration may be more substantial BACKGROUND Observational studies report a relationship between anticholinergic drug scale ( ADS ) score and cognitive function . This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population . METHODS This r and omized , controlled , single-blinded trial , recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway . The participants were r and omly allocated ( 1:1 ) to intervention or control . The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug review s. Primary end point was Consortium to Establish a Registry for Alzheimer 's Disease 10-wordlist test for immediate recall . Secondary end points were Mini-Mental Sate Examination , delayed recall and recognition of words , saliva flow , and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks , and the study groups were compared after adjusting for baseline differences . RESULTS Eighty-seven patients were included . The median ADS score was reduced by 2 units ( p < .0001 ) in the intervention group and remained unchanged in the control group . After 8 weeks , the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group ( 95 % confidence interval [ CI ] : -0.91 , 2.05 ; p = .48 ) . The study groups did not differ significantly in any of the other cognitive end points , salvia flow , or SAA at either follow-up ( p > .18 ) . CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function  in nursing home residents . Moreover , the drug changes did not reduce SAA or mouth dryness significantly , which might indicate limited applicability of the ADS score to prevent prescription risks in this population PURPOSE Overactive bladder is common in the elderly population , which is susceptible to cognitive disorders and drug induced cognitive impairment . Existing overactive bladder treatments may cause adverse events , such as cognitive impairment , due to antagonism of the M1 receptor in the central nervous system . In this study we evaluated the effect of darifenacin , an M3 selective antagonist , on cognitive function in elderly volunteers without clinical dementia . MATERIAL S AND METHODS This double-blind , 3-period crossover study r and omized 129 volunteers 65 years or older with no/mild cognitive impairment to receive 3 of 5 treatments , namely darifenacin controlled release ( 3.75 , 7.5 or 15 mg once daily ) , darifenacin immediate-release ( 5 mg 3 times daily ) or matching placebo for 14 days . Each treatment period was separated by 7 days of washout . Cognitive function tests were completed at baseline and at treatment end . RESULTS For the primary end points of memory scanning sensitivity , speed of choice reaction time and word recognition sensitivity , there were no statistically significant differences for darifenacin vs placebo . There were no statistically significant differences in secondary variables except memory scanning speed , which increased in all groups relative to baseline , but improvement was greater with placebo than with 3.75 mg darifenacin . Darifenacin treatment was not associated with changes in alertness , contentment or calmness , which are likely to be clinical ly relevant . Darifenacin was well tolerated . CONCLUSIONS : In elderly volunteers 2 weeks of treatment with darifenacin had no effect on cognitive function compared with baseline and it was not significantly different from placebo . This may be related to its M3 receptor selectivity with negligible M1 receptor antagonism Abstract Objective To assess the potential of anticholinergic drugs as a cause of  non-degenerative mild cognitive impairment in elderly people . Design Longitudinal cohort study . Setting 63 r and omly selected general practice s in the Montpellier region of southern France . Participants 372 people aged > 60 years without dementia at recruitment . Main outcome measures Anticholinergic burden from drug use , cognitive examination , and neurological assessment . Results 9.2 % of subjects continuously used anticholinergic drugs during the year before cognitive assessment . Compared with non-users , they had poorer performance on reaction time , attention , delayed non-verbal memory , narrative recall , visuospatial construction , and language tasks but not on tasks of reasoning , immediate and delayed recall of wordlists , and implicit memory . Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35 % of non-users , and anticholinergic drug use was a strong predictor of mild cognitive impairment ( odds ratio 5.12 , P = 0.001 ) . No difference was found between users and non-users in risk of developing dementia at follow-up after eight years . Conclusions Elderly people taking anticholinergic drugs  had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired , although not at increased risk for dementia . Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors OBJECTIVES To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men . DESIGN Prospect i ve cohort study . SETTING A Department of Veterans Affairs primary care clinic . PARTICIPANTS Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension . MEASUREMENTS The outcomes were measured using the Hopkins Verbal Recall Test ( HVRT ) for short-term memory and the instrumental activity of daily living ( IADL ) scale for executive function at baseline and during follow-up . Anticholinergic medication use was ascertained using participants ' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anticholinergic score . RESULTS Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs . On average , a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point ( 95 % confidence interval (CI)= 0.05 - 0.58 ) and 0.10-point ( 95 % CI=0.04 - 0.17 ) decrease in the HVRT and IADLs , respectively , independent of other potential risk factors for cognitive impairment , including age , education , cognitive and physical function , comorbidities , and severity of hypertension . The association was attenuated but remained statistically significant with memory ( 0.29 , 95 % CI=0.01 - 0.56 ) and executive function ( 0.08 , 95 % CI=0.02 - 0.15 ) after further adjustment for concomitant non-anticholinergic medications . CONCLUSION Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men . Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects The pathogenesis of delirium in acute stroke is incompletely understood . The use of medications with anticholinergic ( ACH ) activity is associated with an increased frequency of delirium . We hypothesized that the intake of medications with ACH activity is associated with delirium in acute stroke patients . Delirium was assessed using the DSM‐IV‐TR criteria and the Delirium Rating Scale , in a sample of consecutive patients with an acute ( ≤4 days ) cerebral infa rct or intracerebral haemorrhage ( ICH ) . We performed a gender and age matched case – control study . Twenty‐two delirious stroke patients ( cases ) and 52 non‐delirious patients ( controls ) were compared concerning the intake of  ACH medications ( i ) before stroke , ( ii ) during hospitalization but before the assessment . The variables associated with delirium on bivariate analysis were entered in a stepwise logistic regression analysis . The final regression model ( Nagelkerke R2 = 0.65 ) retained  non‐neuroleptics ACH medication during hospitalization ( OR = 24.4 ; 95 % CI = 2.18–250 ) , medical complications ( OR = 20.8 ; 95 % CI = 3.46–125 ) , ACH medication taken before stroke ( OR = 17.5 ; 95 % CI = 1.00–333.3 ) and ICH ( OR = 16.9 ; 95 % CI = 2.73–100 ) as independent predictors of delirium . This preliminary result indicates that drugs with subtle ACH activity play a role in the pathogeneses of delirium in acute stroke . Medication with ACH activity should be avoided in acute stroke patients BACKGROUND The use of drugs with anticholinergic adverse effects is often deemed inappropriate in elderly ( aged > or = 65 years ) patients , yet studies continue to show extensive use in this population at high risk for adverse drug events ( ADEs ) . The burden of drug-related anticholinergic symptoms in community-dwelling elderly patients has not been well described . OBJECTIVE The aim of this study was to assess the prevalence of anticholinergic symptoms , corresponding symptom burden , and anticholinergic-related ADEs in a sample of community-dwelling elderly veterans . METHODS This prospect i ve cohort study was conducted at the primary care clinics at the Veterans Affairs Medical Center ( VAMC ) , Iowa City , Iowa . The study sample included r and omly selected patients with intact cognitive function attending the VAMC and prescribed > or = 5 scheduled medications . Data on current prescription and nonprescription drug use were elicited by a trained research assistant and a clinical pharmacist from patient interviews and electronic medical records . The prevalence and severity of 7 anticholinergic symptoms ( dry mouth , constipation , blurred vision , confusion , urinary hesitation , dry eyes , and drowsiness ) were assessed at baseline . The occurrence of ADEs at 12 weeks was compared between patients using anticholinergic drugs and those not using them . RESULTS 
    Output:
    
agent
medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function , but limited evidence exists for delirium or mortality outcomes
***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: OBJECTIVES To investigate the effects of darifenacin controlled-release ( CR ) and oxybutynin extended-release ( ER ) on cognitive function ( particularly memory ) in older subjects . METHODS Healthy subjects ( n=150 ) > /=60 years were r and omised to darifenacin , oxybutynin ER or placebo in a multicentre , double-blind , double-dummy , parallel-group , 3-week study . Doses were administered according to US labels : oxybutynin ER 10 mg once daily ( od ) , increasing to 15 mg od then 20 mg od by week 3 ; darifenacin 7.5 mg od in weeks 1 and 2 , then 15 mg od in week 3 . The primary end point was accuracy on the Name-Face Association Test ( delayed recall ) at week 3 . RESULTS Results of the Name-Face Association Test at week 3 showed no significant difference between darifenacin and placebo on delayed recall ( mean difference , -0.06 , p=0.908 ) . In contrast , oxybutynin ER result ed in memory impairment , with significantly lower scores than placebo and darifenacin ( mean differences , -1.30 , p=0.011 and -1.24 , p=0.022 , respectively ) for delayed recall on the Name-Face Association Test at week 3 . Additional tests of delayed recall indicated significant memory impairment with oxybutynin ER versus placebo at certain time points , whereas darifenacin was similar to placebo . No between-treatment differences were detected in self-rated memory , demonstrating that subjects were unaware of memory deterioration . CONCLUSIONS While darifenacin had no significant effects on memory versus placebo , oxybutynin ER caused significant memory deterioration ( magnitude of effect comparable to brain aging of 10 years ) . The results also demonstrate that subjects may not recognise/report memory deterioration INTRODUCTION Anti-cholinergic medications have been associated with increased risks of cognitive impairment , premature mortality and increased risk of hospitalisation . Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer , yet little is known about associated adverse outcomes in this setting . METHODS A sub study of 112 participants in a r and omised control trial who had cancer and an Australia modified Karnofsky Performance Scale ( AKPS ) score ( AKPS ) of 60 or above , explored survival and health service utilisation ; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale ( modified version ) longitudinally to death . A st and ardised starting point for prospect ively calculating survival was an AKPS of 60 or above . RESULTS Baseline entry to the sub- study was a mean 62 + /- 81 days ( median 37 , range 1 - 588 ) days before death ( survival ) , with mean of 4.8 ( median 3 , SD 4.18 , range 1 - 24 ) study assessment s in this time period . Participants spent 22 % of time as an inpatient . There was no significant association between anti-cholinergic score and time spent as an inpatient ( adjusted for survival time ) ( p = 0.94 ) ; or survival time . DISCUSSION No association between anti-cholinergic load and survival or time spent as an inpatient was seen . Future studies need to include cognitively impaired population s where the risks of symptomatic deterioration may be more substantial BACKGROUND Observational studies report a relationship between anticholinergic drug scale ( ADS ) score and cognitive function . This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population . METHODS This r and omized , controlled , single-blinded trial , recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway . The participants were r and omly allocated ( 1:1 ) to intervention or control . The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug review s. Primary end point was Consortium to Establish a Registry for Alzheimer 's Disease 10-wordlist test for immediate recall . Secondary end points were Mini-Mental Sate Examination , delayed recall and recognition of words , saliva flow , and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks , and the study groups were compared after adjusting for baseline differences . RESULTS Eighty-seven patients were included . The median ADS score was reduced by 2 units ( p < .0001 ) in the intervention group and remained unchanged in the control group . After 8 weeks , the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group ( 95 % confidence interval [ CI ] : -0.91 , 2.05 ; p = .48 ) . The study groups did not differ significantly in any of the other cognitive end points , salvia flow , or SAA at either follow-up ( p > .18 ) . CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function  in nursing home residents . Moreover , the drug changes did not reduce SAA or mouth dryness significantly , which might indicate limited applicability of the ADS score to prevent prescription risks in this population PURPOSE Overactive bladder is common in the elderly population , which is susceptible to cognitive disorders and drug induced cognitive impairment . Existing overactive bladder treatments may cause adverse events , such as cognitive impairment , due to antagonism of the M1 receptor in the central nervous system . In this study we evaluated the effect of darifenacin , an M3 selective antagonist , on cognitive function in elderly volunteers without clinical dementia . MATERIAL S AND METHODS This double-blind , 3-period crossover study r and omized 129 volunteers 65 years or older with no/mild cognitive impairment to receive 3 of 5 treatments , namely darifenacin controlled release ( 3.75 , 7.5 or 15 mg once daily ) , darifenacin immediate-release ( 5 mg 3 times daily ) or matching placebo for 14 days . Each treatment period was separated by 7 days of washout . Cognitive function tests were completed at baseline and at treatment end . RESULTS For the primary end points of memory scanning sensitivity , speed of choice reaction time and word recognition sensitivity , there were no statistically significant differences for darifenacin vs placebo . There were no statistically significant differences in secondary variables except memory scanning speed , which increased in all groups relative to baseline , but improvement was greater with placebo than with 3.75 mg darifenacin . Darifenacin treatment was not associated with changes in alertness , contentment or calmness , which are likely to be clinical ly relevant . Darifenacin was well tolerated . CONCLUSIONS : In elderly volunteers 2 weeks of treatment with darifenacin had no effect on cognitive function compared with baseline and it was not significantly different from placebo . This may be related to its M3 receptor selectivity with negligible M1 receptor antagonism Abstract Objective To assess the potential of anticholinergic drugs as a cause of  non-degenerative mild cognitive impairment in elderly people . Design Longitudinal cohort study . Setting 63 r and omly selected general practice s in the Montpellier region of southern France . Participants 372 people aged > 60 years without dementia at recruitment . Main outcome measures Anticholinergic burden from drug use , cognitive examination , and neurological assessment . Results 9.2 % of subjects continuously used anticholinergic drugs during the year before cognitive assessment . Compared with non-users , they had poorer performance on reaction time , attention , delayed non-verbal memory , narrative recall , visuospatial construction , and language tasks but not on tasks of reasoning , immediate and delayed recall of wordlists , and implicit memory . Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35 % of non-users , and anticholinergic drug use was a strong predictor of mild cognitive impairment ( odds ratio 5.12 , P = 0.001 ) . No difference was found between users and non-users in risk of developing dementia at follow-up after eight years . Conclusions Elderly people taking anticholinergic drugs  had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired , although not at increased risk for dementia . Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors OBJECTIVES To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men . DESIGN Prospect i ve cohort study . SETTING A Department of Veterans Affairs primary care clinic . PARTICIPANTS Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension . MEASUREMENTS The outcomes were measured using the Hopkins Verbal Recall Test ( HVRT ) for short-term memory and the instrumental activity of daily living ( IADL ) scale for executive function at baseline and during follow-up . Anticholinergic medication use was ascertained using participants ' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anticholinergic score . RESULTS Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs . On average , a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point ( 95 % confidence interval (CI)= 0.05 - 0.58 ) and 0.10-point ( 95 % CI=0.04 - 0.17 ) decrease in the HVRT and IADLs , respectively , independent of other potential risk factors for cognitive impairment , including age , education , cognitive and physical function , comorbidities , and severity of hypertension . The association was attenuated but remained statistically significant with memory ( 0.29 , 95 % CI=0.01 - 0.56 ) and executive function ( 0.08 , 95 % CI=0.02 - 0.15 ) after further adjustment for concomitant non-anticholinergic medications . CONCLUSION Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men . Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects The pathogenesis of delirium in acute stroke is incompletely understood . The use of medications with anticholinergic ( ACH ) activity is associated with an increased frequency of delirium . We hypothesized that the intake of medications with ACH activity is associated with delirium in acute stroke patients . Delirium was assessed using the DSM‐IV‐TR criteria and the Delirium Rating Scale , in a sample of consecutive patients with an acute ( ≤4 days ) cerebral infa rct or intracerebral haemorrhage ( ICH ) . We performed a gender and age matched case – control study . Twenty‐two delirious stroke patients ( cases ) and 52 non‐delirious patients ( controls ) were compared concerning the intake of  ACH medications ( i ) before stroke , ( ii ) during hospitalization but before the assessment . The variables associated with delirium on bivariate analysis were entered in a stepwise logistic regression analysis . The final regression model ( Nagelkerke R2 = 0.65 ) retained  non‐neuroleptics ACH medication during hospitalization ( OR = 24.4 ; 95 % CI = 2.18–250 ) , medical complications ( OR = 20.8 ; 95 % CI = 3.46–125 ) , ACH medication taken before stroke ( OR = 17.5 ; 95 % CI = 1.00–333.3 ) and ICH ( OR = 16.9 ; 95 % CI = 2.73–100 ) as independent predictors of delirium . This preliminary result indicates that drugs with subtle ACH activity play a role in the pathogeneses of delirium in acute stroke . Medication with ACH activity should be avoided in acute stroke patients BACKGROUND The use of drugs with anticholinergic adverse effects is often deemed inappropriate in elderly ( aged > or = 65 years ) patients , yet studies continue to show extensive use in this population at high risk for adverse drug events ( ADEs ) . The burden of drug-related anticholinergic symptoms in community-dwelling elderly patients has not been well described . OBJECTIVE The aim of this study was to assess the prevalence of anticholinergic symptoms , corresponding symptom burden , and anticholinergic-related ADEs in a sample of community-dwelling elderly veterans . METHODS This prospect i ve cohort study was conducted at the primary care clinics at the Veterans Affairs Medical Center ( VAMC ) , Iowa City , Iowa . The study sample included r and omly selected patients with intact cognitive function attending the VAMC and prescribed > or = 5 scheduled medications . Data on current prescription and nonprescription drug use were elicited by a trained research assistant and a clinical pharmacist from patient interviews and electronic medical records . The prevalence and severity of 7 anticholinergic symptoms ( dry mouth , constipation , blurred vision , confusion , urinary hesitation , dry eyes , and drowsiness ) were assessed at baseline . The occurrence of ADEs at 12 weeks was compared between patients using anticholinergic drugs and those not using them . RESULTS 
    Output:
    