The DOI matches its Crossref record; 41 of the 45 references it cites were found in a registry or an index; 16 of the 25 sources its claims cite were checked for support.
Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study
Open accessAbstract
IMPORTANCE: Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia. OBJECTIVE: To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older. DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018. EXPOSURES: The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date). MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables. RESULTS: Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%. CONCLUSIONS AND RELEVANCE: Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In a large UK nested case-control study, higher cumulative exposure to strong anticholinergic drugs was associated with increased dementia risk, with the strongest associations for antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptics. The authors conclude these drugs should be prescribed with caution in middle-aged and older adults, while noting the observational design cannot establish causality.
Key findings
- Among 58,769 dementia cases and 225,574 matched controls, 56.6% of cases vs 51.0% of controls received at least 1 anticholinergic prescription in the 1 to 11 years before the index date; adjusted OR for >1095 total standardized daily doses (TSDDs) vs nonuse was 1.49 (95% CI, 1.44-1.54), and the population-attributable fraction was 10.3%.
- In the highest exposure category (>1095 TSDDs), adjusted ORs were 1.29 (95% CI, 1.24-1.34) for antidepressants, 1.52 (95% CI, 1.16-2.00) for antiparkinson drugs, 1.70 (95% CI, 1.53-1.90) for antipsychotics, 1.65 (95% CI, 1.56-1.75) for bladder antimuscarinics, and 1.39 (95% CI, 1.22-1.57) for antiepileptic drugs. No significant increases were found for antihistamines, skeletal muscle relaxants, gastrointestinal antispasmodics, antiarrhythmics, or antimuscarinic bronchodilators.
- Associations were stronger in cases diagnosed before age 80: for total exposure >1095 TSDDs, adjusted OR was 1.81 (95% CI, 1.71-1.91) before age 80 vs 1.35 (95% CI, 1.30-1.40) at age 80 or older. For vascular dementia vs Alzheimer disease in the 1- to 11-year window, adjusted ORs for >1095 TSDDs were 1.68 (95% CI, 1.57-1.79) and 1.37 (95% CI, 1.30-1.44), respectively.
- The antipsychotic association was not statistically significant in the 5- to 20-year exposure window: adjusted OR for >1095 TSDDs was 1.23 (95% CI, 0.93-1.62), suggesting possible protopathic bias.
Methods
- Nested case-control study within the QResearch database, including patients aged 55 years and older registered January 1, 2004, to January 31, 2016. The base cohort comprised 3,638,582 individuals; 128,517 were diagnosed with dementia during 20,005,739 person-years of follow-up. After exclusions, 58,769 cases and 225,574 controls were matched 5:1 by age, sex, general practice, and calendar time; primary analyses required at least 11 years of recorded data before the index date.
- Exposure was based on 56 anticholinergic drugs identified from Beers criteria, the Anticholinergic Cognitive Burden scale, a systematic review, and the British National Formulary. Total standardized daily doses (TSDDs) were calculated over the 1 to 11 years before the index date, excluding prescriptions in the prior year; sensitivity windows were 3 to 13 years and 5 to 20 years. Exposure categories were 0, 1-90, 91-365, 366-1095, and >1095 TSDDs.
- Conditional logistic regression estimated adjusted odds ratios, accounting for demographic factors, comorbidities, and other medications. Sensitivity analyses included multiple imputation, WHO-defined daily doses, and restriction to drugs included by Gray et al. Statistical significance was set at P < .01 (2-tailed).
Limitations
- The paper states that some patients may not have taken prescribed medication or the prescribed dose, leading to exposure misclassification; if nondifferential, this would tend to reduce odds ratios and might explain the lack of association for antihistamines and the highest antivertigo exposure category.
- Dementia identification relied on recorded diagnoses or acetylcholinesterase-inhibitor treatment rather than screening the entire population, so there will be underascertainment of dementia cases and some controls may have had undiagnosed dementia, again likely underestimating associations.
- The paper notes potential residual confounding and indication bias in an observational study. Protopathic bias was reduced by excluding prescriptions in the year before diagnosis and in 3- and 5-year sensitivity analyses, but the antipsychotic association was not significant when prescriptions in the 5 years before diagnosis were excluded, suggesting possible protopathic bias; some prodromal symptoms can emerge up to 10 years before diagnosis.
- The paper states the observational study cannot evaluate causality. The text also makes evident that some drug-type analyses had small numbers—skeletal muscle relaxants and antiarrhythmics—giving imprecise estimates.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
16 of 25 cited sources checked · 8 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A study by Richardson et al,12 using another United Kingdom primary care database (CPRD), reported findings similar to ours, despite some differences in the drugs included, exposure measures used, exposure windows, and the confounding variables accounted for.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
What the sources say
- Partly supportedcites [12] Richardson K, Fox C, Maidment I, Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018; 361: k1315. doi: 10.1136/bmj.k1315 29695481 PMC5915701 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our findings are consistent with other studies, including a US cohort study of 3434 participants,11 which reported a hazard ratio of 1.54 (95% CI, 1.21-1.96) for the highest exposure category (>1095 TSDDs), similar to our AOR of 1.49 (95% CI, 1.44-1.54).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
What the sources say
- Supportedcites [11] Gray SL, Anderson ML, Dublin S, Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015; 175(3): 401- 407. doi: 10.1001/jamainternmed.2014.7663 25621434 PMC4358759 source
The Methods (Design, Study Setting, and Participants; page unavailable) identify a US cohort with 3,434 eligible participants. The Results passage reports an adjusted dementia hazard ratio of 1.54 (95% CI, 1.21–1.96) for the highest exposure category, >1095 TSDD, compared with non-use. (LLM, conf=0.95)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“We accounted for potential confounding variables identified as risk factors for dementia or indications for anticholinergic drug use,19,20,21,22,23,24,25 including body mass index, calculated as weight in kilograms divided by height in meters squared,20 smoking status,26 alcohol consumption,27 Townsend deprivation score,21 self-assigned ethnic group,28 comorbidities”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Confounding Variables
What the sources say
- Not checked — no full text of the sourcecites [19] Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E Alzheimer’s disease. Lancet. 2011; 377(9770): 1019- 1031. doi: 10.1016/S0140-6736(10)61349-9 21371747 source
- Not checked — no full text of the sourcecites [20] Anstey KJ, Cherbuin N, Budge M, Young J Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev. 2011; 12(5): e426- e437. doi: 10.1111/j.1467-789X.2010.00825.x 21348917 source
- Supportedcites [21] Walters K, Hardoon S, Petersen I, Predicting dementia risk in primary care: development and validation of the Dementia Risk Score using routinely collected data. BMC Med. 2016; 14(1): 6. doi: 10.1186/s12916-016-0549-y 26797096 PMC4722622 source
The Methods (Risk factor measurements) identify BMI among the potential dementia-risk predictors examined, and the Results (Table 2) include BMI in the final risk model. In the citing sentence, this source is cited specifically alongside BMI, which is the part it supports. (LLM, conf=0.91)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“which would equate, for example, to around 20 000 of the 209 600 new cases of dementia per year in the United Kingdom.32”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
What the sources say
- Partly supportedcites [32] Matthews FE, Stephan BCM, Robinson L,; Cognitive Function and Ageing Studies (CFAS) Collaboration A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II. Nat Commun. 2016; 7: 11398. doi: 10.1038/ncomms11398 27092707 PMC4838896 sourceExperimental — accuracy not yet measured
The Results section (‘Population estimates of incidence cases’; page unavailable) estimates 209,600 new dementia cases per year in the UK among people aged 65 and over. The paper does not estimate that 20,000 cases are attributable to anticholinergic drug exposure; that conditional calculation goes beyond what this source reports. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Sensitivity analyses using multiply imputed data (eTable 13 in the Supplement) or restricted to anticholinergic drugs included in the study by Gray et al11 (eTable 14 in the Supplement) did not change study findings.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Additional Analyses
What the sources say
- Supportedcites [11] Gray SL, Anderson ML, Dublin S, Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015; 175(3): 401- 407. doi: 10.1001/jamainternmed.2014.7663 25621434 PMC4358759 source
The citation to Gray et al. identifies the anticholinergic drugs used to define the citing study’s restricted analysis, not the result of that analysis. Gray et al.’s Methods (Anticholinergic Medication Use; page unavailable) state that eTable 1 lists the strong anticholinergic medications included in their study by class. The unchanged findings are attributed to the citing study’s own eTables 13 and 14. (LLM, conf=0.93)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“for example, for the 5 to 20 years before the index date the AOR was 1.44 (95% CI, 1.32-1.57) for more than 1095 TSDDs (Table 4).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusted odds ratios in the highest exposure category (>1095 TSDDs) were 1.29 (95% CI, 1.24-1.34) for antidepressants, 1.52 (95% CI, 1.16-2.00) for antiparkinson drugs, 1.70 (95% CI, 1.53-1.90) for antipsychotics, 1.65 (95% CI, 1.56-1.75) for bladder antimuscarinics, and 1.39 (95% CI, 1.22-1.57) for antiepileptic drugs, all compared with nonuse.”
- Also stated in: § Findings · plain
“there were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotic drugs, bladder antimuscarinics, and antiepileptic drugs after adjusting for confounding variables.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
- Also stated in: § Findings · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusted odds ratios in the highest exposure category (>1095 TSDDs) were 1.29 (95% CI, 1.24-1.34) for antidepressants, 1.52 (95% CI, 1.16-2.00) for antiparkinson drugs, 1.70 (95% CI, 1.53-1.90) for antipsychotics, 1.65 (95% CI, 1.56-1.75) for bladder antimuscarinics, and 1.39 (95% CI, 1.22-1.57) for antiepileptic drugs, all compared with nonuse.”
- Also stated in: § Findings · plain
“there were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotic drugs, bladder antimuscarinics, and antiepileptic drugs after adjusting for confounding variables.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
- Also stated in: § Findings · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusted odds ratios in the highest exposure category (>1095 TSDDs) were 1.29 (95% CI, 1.24-1.34) for antidepressants, 1.52 (95% CI, 1.16-2.00) for antiparkinson drugs, 1.70 (95% CI, 1.53-1.90) for antipsychotics, 1.65 (95% CI, 1.56-1.75) for bladder antimuscarinics, and 1.39 (95% CI, 1.22-1.57) for antiepileptic drugs, all compared with nonuse.”
- Also stated in: § Findings · plain
“there were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotic drugs, bladder antimuscarinics, and antiepileptic drugs after adjusting for confounding variables.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
- Also stated in: § Findings · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusted odds ratios in the highest exposure category (>1095 TSDDs) were 1.29 (95% CI, 1.24-1.34) for antidepressants, 1.52 (95% CI, 1.16-2.00) for antiparkinson drugs, 1.70 (95% CI, 1.53-1.90) for antipsychotics, 1.65 (95% CI, 1.56-1.75) for bladder antimuscarinics, and 1.39 (95% CI, 1.22-1.57) for antiepileptic drugs, all compared with nonuse.”
- Also stated in: § Findings · plain
“there were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, antiparkinson drugs, antipsychotic drugs, bladder antimuscarinics, and antiepileptic drugs after adjusting for confounding variables.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
- Also stated in: § Findings · plain
- Probably not a substantial claim. 20
- It may state two separate claims as one. 24
Every source the paper cites for this claim was checked and supports it.
In the paper
“While both CPRD and QResearch are large United Kingdom databases, QResearch is the most nationally representative, while CPRD is more geographically restricted.36”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
What the sources say
- Supportedcites [36] Kontopantelis E, Stevens RJ, Helms PJ, Edwards D, Doran T, Ashcroft DM Spatial distribution of clinical computer systems in primary care in England in 2016 and implications for primary care electronic medical record databases: a cross-sectional population study. BMJ Open. 2018; 8(2): e020738. doi: 10.1136/bmjopen-2017-020738 29490968 PMC5855245 source
The Discussion calls QResearch the most nationally representative single database, with potential coverage of almost all English CCGs. It also says CPRD cannot provide comprehensive coverage of large parts of the country, particularly northern and eastern England. The comparison concerns geographic representativeness in England at the time studied, not demonstrated coverage across every UK nation. (LLM, conf=0.93)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“This proportion is sizeable and is comparable with estimates for other modifiable risk factors for dementia, such as 5% for midlife hypertension, 3% for diabetes, 14% for later-life smoking, and 6.5% for physical inactivity.1”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
What the sources say
- Could not verifycites [1] Livingston G, Sommerlad A, Orgeta V, Dementia prevention, intervention, and care. Lancet. 2017; 390(10113): 2673- 2734. doi: 10.1016/S0140-6736(17)31363-6 28735855 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Despite these differences, Richardson et al12 also found increases in dementia risk for the groups of antidepressant, urological, and antiparkinson drugs considered and no associations for gastrointestinal or antihistamine drugs.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
What the sources say
- Partly supportedcites [12] Richardson K, Fox C, Maidment I, Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018; 361: k1315. doi: 10.1136/bmj.k1315 29695481 PMC5915701 sourceExperimental — accuracy not yet measured
The Results (Exposure by drug class) report significant associations with dementia for antidepressant, antiparkinson, and urological drugs with an ACB score of 3, and no overall association for antihistamines in that group. But the blanket claim of no associations for gastrointestinal or antihistamine drugs is too broad: gastrointestinal drugs were associated with a minor reduction in risk, and a tentative antihistamine association appeared at more than 365 prescribed daily doses. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A recent larger study12 found varying risks associated with different types of anticholinergic drugs and concluded that further research should examine individual anticholinergic drug classes.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Introduction
What the sources say
- Supportedcites [12] Richardson K, Fox C, Maidment I, Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018; 361: k1315. doi: 10.1136/bmj.k1315 29695481 PMC5915701 source
The Discussion (Strengths and weaknesses in relation to other studies) says this study used a larger sample than earlier work. The Discussion (Conclusion) reports associations for some anticholinergic drug classes but not others, and the Abstract (Conclusions) calls for future research to examine individual classes. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A cohort study11 that reduced protopathic bias by excluding prescriptions in the final year of follow-up found that higher cumulative anticholinergic drug use was associated with a significantly increased risk of dementia but had limited power for analysis of separate types of anticholinergic drug.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Introduction
What the sources say
- Partly supportedcites [11] Gray SL, Anderson ML, Dublin S, Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015; 175(3): 401- 407. doi: 10.1001/jamainternmed.2014.7663 25621434 PMC4358759 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Observational studies of anticholinergic drugs and dementia risk7,8,9,10 have generally been relatively small, only assessed short-term exposure, or were subject to recall bias.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Introduction
What the sources say
- Partly supportedcites [7] Cai X, Campbell N, Khan B, Callahan C, Boustani M Long-term anticholinergic use and the aging brain. Alzheimers Dement. 2013; 9(4): 377- 385. doi: 10.1016/j.jalz.2012.02.005 23183138 PMC3674201 sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe limited long-term evidence and short observation windows, including this study’s one-year design and a prior study’s 3- to 12-month follow-up. The Discussion also identifies a small exposed subgroup. Our copy does not identify recall bias as a limitation of these studies, so it supports only part of the attributed characterization. (LLM, conf=0.83)
- Supportedcites [8] Ancelin ML, Artero S, Portet F, Dupuy A-M, Touchon J, Ritchie K Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006; 332(7539): 455- 459. doi: 10.1136/bmj.38740.439664.DE 16452102 PMC1382539 source
The ‘Use of anticholinergic drugs’ section reports 372 participants, of whom only 30 used anticholinergic drugs throughout the year assessed. The ‘Development of dementia’ section explicitly says small numbers prevented a statistical comparison of dementia conversion rates. This paper therefore exemplifies the small-study limitation in the citing sentence, although its dementia follow-up lasted eight years. (LLM, conf=0.88)
- Partly supportedcites [9] Carrière I, Fourrier-Reglat A, Dartigues JF, Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009; 169(14): 1317- 1324. doi: 10.1001/archinternmed.2009.229 19636034 PMC2933398 sourceExperimental — accuracy not yet measured
The Anticholinergic drug use section says medication use was inventoried for the preceding month, and the Limitations section says precise treatment duration was unavailable. That supports the short-term exposure-measurement concern, but this was a large study with four-year follow-up (Study population), not a small study assessing only short-term outcomes. The Limitations section identifies possible recall bias in self-reported covariates, while the Strengths section says medication use was checked against prescriptions and medications. (LLM, conf=0.85)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We used the approach of Gray et al,11 which included drugs identified as having strong anticholinergic properties by the American Geriatrics Society 2012 Beers Criteria Update Expert Panel.14”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Exposures
What the sources say
- Supportedcites [11] Gray SL, Anderson ML, Dublin S, Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015; 175(3): 401- 407. doi: 10.1001/jamainternmed.2014.7663 25621434 PMC4358759 source
The Methods (Anticholinergic Medication Use) say Gray et al. defined anticholinergic use using medications deemed to have strong anticholinergic activity by an expert panel, citing reference 8. The References identify reference 8 as the American Geriatrics Society’s 2012 Beers Criteria update. Gray et al. also added older medications to that list, which is consistent with the claim that their approach included the panel-identified drugs. (LLM, conf=0.93)
- Supportedcites [14] American Geriatrics Society 2012 Beers Criteria Update Expert Panel American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012; 60(4): 616- 631. doi: 10.1111/j.1532-5415.2012.03923.x 22376048 PMC3571677 source
The Results section says Table 9 lists anticholinergic medications to avoid in older adults, compiled from drugs rated as having strong anticholinergic properties. This supports citing the 2012 AGS Beers Criteria as a source for identifying those drugs; the paper notes that the ratings came from three existing scales. (LLM, conf=0.91)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Each case patient was matched to 5 controls by age (within 1 year), sex, general practice, and calendar time using incidence density sampling.13”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Selection of Cases and Controls
What the sources say
- Partly supportedcites [13] Vandenbroucke JP, Pearce N Case-control studies: basic concepts. Int J Epidemiol. 2012; 41(5): 1480- 1489. doi: 10.1093/ije/dys147 23045208 sourceExperimental — accuracy not yet measured
The sections on cohorts versus dynamic populations and density sampling (page numbers unavailable) explain selecting controls when each case occurs and matching on calendar time. They do not document this study’s five-controls-per-case ratio or its matching criteria of age within one year, sex, and general practice. (LLM, conf=0.88)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The AOR associated with total cumulative anticholinergic exposure in the 1 to 11 years before the index date increased from 1.06 (95% CI, 1.03-1.09) for 1 to 90 TSDDs to 1.49 (95% CI, 1.44-1.54) for more than 1095 TSDDs, compared with nonuse (Table 4).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patterns of risk were similar in the 3- to 13- and 5- to 20-year exposure windows (eTable 6 in the Supplement), except for antipsychotic drug exposure in the 5- to 20-year window, where there were no statistically significant increases in risk; the AOR for more than 1095 TSDDs was 1.23 (95% CI, 0.93-1.62).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For antivertigo/antiemetic drugs, as detailed in Table 5, there was a significantly increased risk associated with 366 to 1095 TSDDs, but not for the highest exposure category.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increased risks identified for specific drug groups in the main analysis remained in these sensitivity analyses except for the association with antipsychotic drugs”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion > Limitations
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no significantly increased risks for antihistamines, gastrointestinal antispasmodics, antimuscarinic bronchodilators, antiarrhythmics, or skeletal muscle relaxants, although the numbers of patients prescribed skeletal muscle relaxants and antiarrhythmic drugs were small, giving imprecise estimates.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Associations were similar in men and women (eTable 9 in the Supplement).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Additional Analyses
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patterns of risk were similar in the 3- to 13- and 5- to 20-year exposure windows (eTable 6 in the Supplement), except for antipsychotic drug exposure in the 5- to 20-year window, where there were no statistically significant increases in risk; the AOR for more than 1095 TSDDs was 1.23 (95% CI, 0.93-1.62).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
- Rests on an assumption: The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This misclassification, if nondifferential, would tend to reduce ORs and might explain the lack of association for antihistamines and the highest exposure category of antivertigo drugs.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion > Limitations
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A limitation is that some patients may not have taken their prescribed medication or not taken the dose prescribed, leading to exposure misclassification.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion > Limitations
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“(4) we used multiple imputation by chained equations to replace missing values for body mass index, smoking status, and alcohol consumption. We created 10 multiply imputed data sets and combined results using Rubin rules29; and”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Statistical Analysis
What the sources say
- Not checked — no full text of the sourcecites [29] Rubin DB Multiple Imputation for Nonresponse in Surveys. Hoboken, NJ: John Wiley & Sons; 1987. doi: 10.1002/9780470316696 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The analysis accounted for a wide range of potential confounding variables, but in an observational study, there is potential for residual confounding and indication bias.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion > Limitations
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Case patients with diagnostic codes for specific subtypes of dementia associated with Huntington disease, Parkinson disease, Creutzfeldt-Jakob disease, or human immunodeficiency virus (HIV) were excluded, as were patients diagnosed with Parkinson disease, Huntington disease, or multiple sclerosis to reduce indication bias.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Selection of Cases and Controls
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“As a sensitivity analysis we used World Health Organization (WHO)-defined daily dose (DDD) values (https://www.whocc.no/atc_ddd_index/) to standardize the prescribed doses.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Exposures
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We endeavored to reduce protopathic bias by excluding prescriptions in the year before diagnosis and in the 3 and 5 years before diagnosis in sensitivity analyses.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion > Limitations
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This means that there will be underascertainment of dementia cases, so some controls may have had undiagnosed dementia, which again would tend to underestimate associations with drug exposure.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion > Limitations
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The present study adds further evidence of potential risks associated with strong anticholinergic drugs, particularly those that are antidepressants, bladder antimuscarinic drugs, antiparkinson drugs, and epilepsy drugs.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
- Rests on an assumption: Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Nevertheless, the possibility of residual confounding remains, and it is impossible to entirely exclude protopathic effects arising from treatment for very early preclinical effects of dementia.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For some drug types, numbers were too small to allow analysis for the 5 to 20 years before the index date (eTable 7 in the Supplement).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Results > Associations With Dementia
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
- Rests on an assumption: Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We included a large representative sample of people diagnosed with dementia and matched controls.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“data were recorded prospectively, so results are not susceptible to recall bias.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Comprehensive data on prescriptions meant that we could derive a measure of total anticholinergic drug exposure, which accounted for the quantity and dose prescribed.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“With our larger sample size we could also examine specific types of anticholinergic drugs and account for a broader range of confounders.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All eligible case patients and controls were included, so there is no selection bias due to nonresponse”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To reduce protopathic biases, we did not include prescriptions issued in the year before the index date.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Exposures
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Controls were excluded if they had a diagnosis of Parkinson disease, Huntington disease, or multiple sclerosis.”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Selection of Cases and Controls
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“We also included additional drugs in the Beers 2015 updated list of strong anticholinergic drugs,15 drugs listed as having a high anticholinergic burden in the Anticholinergic Cognitive Burden scale,16 or identified as high-potency anticholinergics in a systematic review,17 and some further drugs identified as having substantial anticholinergic properties in the British National Formulary”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Exposures
What the sources say
- Not checked — no full text of the sourcecites [15] By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015; 63(11): 2227- 2246. doi: 10.1111/jgs.13702 26446832 source
- Not checked — no full text of the sourcecites [16] Boustani M, Campbell N, Munger S, Maidment I, Fox C Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008; 4(3): 311- 320. doi: 10.2217/1745509X.4.3.311 source
- Not checked — no full text of the sourcecites [17] Durán CE, Azermai M, Vander Stichele RH Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol. 2013; 69(7): 1485- 1496. doi: 10.1007/s00228-013-1499-3 23529548 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the primary analyses, case patients and controls were only included if they had at least 11 years of recorded data prior to the index date, so that anticholinergic drug exposure could be assessed over a complete period of 10 years (excluding the 1-year period prior to the index date).”
§ Anticholinergic Drug Exposure and the Risk of Dementia > Methods > Selection of Cases and Controls
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
Clinical codes recorded in QResearch practice records or linked Office of National Statistics death records accurately identify dementia cases.
“Case patients were those diagnosed with dementia during follow-up, identified using clinical codes recorded in the practice records or linked Office of National Statistics death records.”
The paper relies on this without support.
Prescriptions recorded in QResearch accurately reflect actual anticholinergic drug exposure.
“We extracted details of prescriptions for the included anticholinergic drugs.”
The paper relies on this without support.
The measured confounding variables sufficiently control for confounding of the association between anticholinergic drug use and dementia.
“We used conditional logistic regression to estimate odds ratios (ORs) adjusted for the confounding variables.”
The paper relies on this without support.
The QResearch cohort is representative of the British population aged 55 years and older.
“This study was designed to assess the association between cumulative anticholinergic drug use and risk of dementia in a large, representative British population.”
The paper relies on this without support.
Excluding prescriptions issued in the year before the index date is sufficient to remove protopathic bias.
“To reduce protopathic biases, we did not include prescriptions issued in the year before the index date.”
The paper relies on this without support.
Prescribed anticholinergic medication is a valid proxy for actual anticholinergic drug exposure in the study population.
“A limitation is that some patients may not have taken their prescribed medication or not taken the dose prescribed, leading to exposure misclassification.”
The paper relies on this without support.
Recorded diagnoses of dementia or prescriptions for acetylcholinesterase-inhibiting drugs in QResearch accurately identify cases of dementia.
“Our identification of patients with dementia was based on recorded diagnoses or treatment with acetylcholinesterase-inhibiting drugs rather than screening of the entire study population.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This association between anticholinergic antidepressants and dementia aligns with previous longitudinal cohort studies indicating that anticholinergic medications negatively affect cognitive performance [15, 31, 32, 43, 44].”
From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [15]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Anticholinergic drugs block acetylcholine, a neurotransmitter essential for cognitive function, and have been associated with an increased risk of dementia in older adults [15, 31, 32].”
From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Anticholinergic drugs block acetylcholine, a neurotransmitter essential for cognitive function, and have been associated with an increased risk of dementia in older adults [15, 31, 32].”
From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reference accessed before its stated publication date
MinorReference 5 says the document was accessed on May 16, 2018, but gives its publication date as June 20, 2018.
“Published June 20, 2018.”
“Accessed May 16, 2018.”
Citations
Cites
Multiple Imputation for Nonresponse in Surveys
Rubin, D. B. (1987) · Wiley Series in Probability and Statistics · doi:10.1002/9780470316696 · Cited by 20,701
Dementia prevention, intervention, and care
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Anstey, K. J., von Sanden, C., Salim, A., & O'Kearney, R. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm116 · Cited by 921
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Research works printed but not linked: 2
- American Geriatrics Society 2012 Beers Criteria Update Expert Panel, 2012, American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults., J Am Geriatr Soc, 60, 616, 10.1111/jgs.2012.60.issue-4 · DOI
- Semla, 2010, Geriatric Dosage Handbook: Including Clinical Recommendations and Monitoring Guidelines
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Liu, X., Lin, T.-F., Jiang, Y.-W., Luo, S., Chen, S., Chai, Y., Yang, Z. L., Wei, Y., Wang, H., Li, X., et al. (2026) · Psychological Medicine · doi:10.1017/s0033291726104942
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Falfaly, Z., Peterson, G. M., Bezabhe, W. M. M., & Salahudeen, M. S. (2026) · Medical Sciences · doi:10.3390/medsci14040426
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Metadata
- Authors
- Coupland, C. A. C., Hill, T., Dening, T., Morriss, R., Moore, M., & Hippisley-Cox, J.
- Affiliations
- University of Nottingham (GB)
- University of Southampton (GB)
- Division of Primary Care, University of Nottingham, Nottingham, England
- Corresponding author
- Coupland, Carol A. C.
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2019-08-01
- Volume
- 179
- Issue
- 8
- Pages
- 1084
- ISSN
- 2168-6106 (ISSN-L)
- PMC
- PMC6593623
- OpenAlex
- W2939971450
- Semantic Scholar
- a4a5dce2c4cc646d992a72675f810f737c1db9c4
- Cited by
- 637
- References
- 45
- Citations by year
- 2026: 81 · 2025: 80 · 2024: 93 · 2023: 61 · 2022: 78 · 2021: 93 · 2020: 122 · 2019: 27
- FWCI
- 55.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- JAMA Internal Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Oxford University Research Archive (ORA) (University of Oxford) (submittedVersion, cc-by)
- Funders
- National Institute for Health and Care Research (NF-SI-0617-10016)
- NIHR School for Primary Care Research
- NIHR Nottingham Biomedical Research Centre
- Faculty of Medicine and Health, University of Sydney
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- anticholinergic agents, dementia risk, cumulative drug exposure, antipsychotic drugs, antiparkinsonian drugs, anticholinergic effects, older adults, QResearch database, cognitive decline, polypharmacy, Parkinson's disease, Alzheimer's disease, dementia with Lewy bodies, vascular dementia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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