The cognitive impact of anticholinergics: A clinical review

Figures & data

Figure 1 Selection process for study inclusion.

Table 1 Clinical studies evaluating anticholinergic activity

Reference	Design	Setting	Sample size/Mean age	Critical appraisal
Ancelin et al^Citation12	Longitudinal cohort	63 general practices	372/80	Good
Bottigi et al^Citation13	Longitudinal cohort	Patients from Aging Alzheimer’s Disease Research Center	592/73	Fair
Caeiro et al^Citation14	Case-control	Stroke patients from Neurology	74/65	Good
Chew et al^Citation15	Cross-sectional	Psychiatric and geriatric clinic inpatients	26/83.6	Fair
Flacker et al^Citation16	Cross-sectional	Acutely ill medical inpatients	67/85	Good
Flacker et al^Citation17	Cross-sectional	Nursing home residents with fever	22/88	Good
Golinger et al^Citation18	Longitudinal cohort	Surgical Intensive care unit	25/58	Poor
Han et al^Citation19	Longitudinal cohort	Hospitalized patients with delirium	278/83	Good
Hilmer et al ^Citation20	Cross-sectional	Community-based	3075/73	Good
Lechevalier et al^Citation21	Cross-sectional	Community-based	1780/77	Good
Lu et al^Citation22	Longitudinal cohort	Community-based	69/76	Good
Mach et al^Citation23	Case-control	VA hospital medical units	22/71	Fair
Marcantonio et al^Citation24	Cross-sectional	Post-surgical patients	91/73	Good
Miller et al ^Citation25	Longitudinal cohort	Surgical patients	30/67	Good
Minzenberg et al^Citation26	Cross-sectional	Outpatients from VA medical center	106/40	Fair
Mondimore et al^Citation27	Cross-sectional	Post-ECT inpatients	20/49	Fair
Mulsant et al^Citation6	Cross-sectional	Community patients	201/78	Good
Mussi et al^Citation28	Cross-sectional	Geriatric inpatients	61/79	Fair
Nebes et al^Citation29	Cross-sectional	Psychiatric and geriatric inpatients	36/69	Fair
Nebes et al^Citation30	Cross-sectional	Community based	134/75	Fair
Patten et al^Citation31	Case-control	Psychiatric inpatients	425/65	Fair
Plaschke et al^Citation32	Longitudinal cohort	Medical and surgical intensive care unit with delirium	37/64	Fair
Roe et al^Citation33	Case-control	Community-based	836/75	Fair
Rovner et al^Citation34	Cross-sectional	Nursing home patients	22/81	Fair
Thienhaus et al^Citation35	Case-control	Psychiatric and geriatric inpatients	28/65	Fair
Tollefson et al^Citation5	Case-control	Nursing home patients	34/79	Good
Tune et al^Citation10	Longitudinal cohort	Cardiac surgery patients	29/55	Fair

Abbreviations: VA, Veteran Administration; ECT, electro-convulsive therapy.

Notes: *Articles were appraised on the following criteria: inclusion of longitudinal data; adjustments for age, gender, baseline cognition, or other relevant parameters; attrition rate <40%; use of standardized measurements for cognition and delirium; minimum selection bias; and minimum recall bias.

Table 2 Association between serum anticholinergic activities and cognition

Reference	CI	Delirium
Ancelin et al^Citation12	+ (Stockholm)	N/A
Chew et al^Citation15*	+ (MMSE, SIB)	N/A
Flacker et al^Citation16	N/A	+ (CAM, DSI)
Flacker et al^Citation17	N/A	+ (CAM)
Golinger et al^Citation18	N/A	+ (DSM-III)
Mach et al^Citation23	N/A	+ (DSM-III-R)
Miller et al^Citation25	− (MMSE)	+ (SDC)
Mondimore et al^Citation27	+ (MMSE)	N/A
Mulsant et al^Citation6	+ (MMSE)	N/A
Mussi et al^Citation28	N/A	+ (CAM)
Nebes et al^Citation29	+ (DSM-IV)	N/A
Nebes et al^Citation30	+ (Verbal N Back test)	N/A
Plaschke et al^Citation32	N/A	− (CAM-ICU)
Rovner et al^Citation34*	+ (MMSE, DSM-III)	N/A
Thienhaus et al^Citation35*	+ (MMSE)	N/A
Tollefson et al^Citation5*	+ (MMSE, BCRS, WMS)	+ (SDC)
Tune et al^Citation10	N/A	+ (Clinical)

Abbreviations: CI, cognitive impairment, includes mild cognitive impairment (MCI), or worsening function in those with baseline diagnosis of CI; “+”: statistically significant association; “−”: no significant association; “N/A”: not assessed; Stockholm, Stockholm consensus group criteria for diagnosing mild cognitive impairment; SAA, serum anticholinergic activity; MMSE, Mini-Mental state exam; SIB, severe impairment battery; TMT, Trail Making Test; WLMT, Word List Memory Test; BCRS, Brief Cognitive Rating scale; WMS, Wechsler Memory Scale; SDC, Saskatoon Delirium Checklist; CAM, Confusion Assessment Method; DSI, Delirium symptom Interview; DI, Delirium Index; IST, Isaacs’ Set Test; BVRT, Benton Visual Retention Test; DRS, Dementia Rating Scale; DSST, Digit Symbol Substitution Test (derived from the WMS).

Note: *Indicates the study population had baseline cognitive impairment.

Table 3 Association between anticholinergic activity assessed by expert-based drug list and cognition

Reference	CI	Delirium
Bottigi et al^Citation13	+ (MMSE, TMT, WLMT)	N/A
Caeiro et al^Citation14	N/A	+ (DSM-IV-TR)
Han et al^Citation19	N/A	+ (DI)
Hilmer et al ^Citation20	+ (DSST)	N/A
Lechevalier et al^Citation21	+ (MMSE, BVRT, IST)	N/A
Lu et al^Citation22*	+ (MMSE, DRS)	N/A
Marcantonio et al^Citation24	N/A	− (CAM)
Minzenberg et al^Citation26	+ (WMS)	N/A
Patten et al^Citation31	N/A	+ (DSM-IV)
Roe et al^Citation33*	+ (Initiation of Donepezil therapy)	N/A

Abbreviations: CI, cognitive impairment, includes mild cognitive impairment (MCI), or worsening function in those with baseline diagnosis of CI; “+”:statistically significant association; “−”: no significant association; “N/A”: not assessed; MMSE, Mini-Mental State Exam; TMT, Trail Making Test; WLMT, Word List Memory Test; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; WMS, Wechsler Memory Scale; CAM, Confusion Assessment Method; IST, Isaacs’ Set Test; BVRT, Benton Visual Retention Test; DRS, Dementia Rating Scale; DSST, Digit Symbol Substitution Test (derived from the WMS).

Note: *Indicates the study population had baseline cognitive impairment.

Figure 2 Proposed algorithm for the clinical approach to older adults prescribed anticholinergic medications.

Abbreviations: CAM, Confusion Assessment Method; TICS, telephone interview for cognitive status; MMSE, Mini-Mental Status Exam.

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