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Cited by 1Dementia and Cognitive Impairment ResearchPharmaceutical Practices and Patient OutcomesTreatment of Major Depression

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index; 6 of the 30 sources its claims cite were checked for support.

Understanding the Association Between Antidepressants and the Risk of Being Diagnosed with Dementia in Older People: A Self-Controlled Case Series Study

Open access
Xu, Zhongzhi, Yang, Jiannan, Lau, Kui Kai, Yip, Paul S.F., Wong, Ian C.K., Zhang, Qingpeng·2020·Journal of Alzheimer's Disease
DOI 10.3233/jad-200875
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Abstract

Background: Given concerns about adverse outcomes for older people taking antidepressants in the literature, we investigated whether taking antidepressants elevates the risk of dementia. Objective: This study aims to investigate the putative association of antidepressants with the risk of dementia. Methods: We conducted a population-based self-controlled case series analysis of older people with dementia and taking antidepressants, using territory-wide medical records of 194,507 older patients collected by the Hospital Authority of Hong Kong, to investigate the association between antidepressant treatment and the risk of developing dementia in older people. Results: There was a significantly higher risk of being diagnosed with dementia during the pre-drug-exposed period (incidence rate ratio (IRR) 20.42 (95% CI: 18.66–22.34)) compared to the non-drug-exposed baseline period. The IRR remained high during the drug-exposed period (IRR 8.86 (7.80–10.06)) before returning to a baseline level after washout (IRR 1.12 (0.77–1.36)). Conclusion: The higher risk of dementia before antidepressant treatment may be related to emerging psychiatric symptoms co-occurring with dementia, which trigger medical consultations that result in a decision to begin antidepressants. Our findings do not support a causal relationship between antidepressant treatment and the risk of dementia.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a territory-wide Hong Kong self-controlled case series of 2,386 older antidepressant users with first-ever dementia, dementia diagnosis risk was highest before antidepressant initiation (IRR 20.42) and remained elevated during exposure (IRR 8.86), but returned to baseline after washout (IRR 1.12). The authors conclude their findings do not support a causal association between antidepressant treatment and dementia; the pre-treatment risk may reflect emerging psychiatric symptoms co-occurring with dementia.

Key findings

  • Among 194,507 people aged 65+ years, 24,646 (12.6%) received a dementia diagnosis, 18,825 had first lifetime diagnoses, and 3,757 (20.0%) had been prescribed antidepressants; after exclusions, 2,386 eligible participants were modeled (837 men, 35.1%; mean age 81.7 years, SD 7.26).
  • Compared with baseline, the age-adjusted IRR for dementia diagnosis was 20.42 (95% CI 18.66–22.34) during the 50-day pre-exposure period, 8.86 (7.80–10.06) during the index drug-exposed period, 4.83 (3.28–7.13) during subsequent drug-exposed periods, and 1.12 (0.77–1.36) during washout.
  • Spline-based SCCS showed dementia risk increased significantly before antidepressant initiation and peaked within 50 days before treatment; subcategory analyses for TCAs, SSRIs, and other antidepressants were consistent with the main results.
  • Post-hoc analysis found first-ever dementia prevalence among people with depression-related disorders was 26.6% (648/2,432), 2.7 times the 9.7% (18,825/194,507) prevalence in the whole population.

Methods

  • Population-based SCCS using territory-wide deidentified Hospital Authority of Hong Kong electronic health records; participants were aged 65+, had a first-ever dementia diagnosis during January 1, 2008–December 31, 2010 or death, and had at least one antidepressant prescription (BNF 4.3.x), with a five-year pre-study window to exclude prior dementia.
  • Exclusions were antidepressant exposure shorter than seven days and/or overlapping washout and subsequent exposure; 1,300 and 71 patients were excluded respectively.
  • Main analysis calculated crude incidence rates per 1,000 patient-days and age-adjusted IRRs using a non-homogeneous age-dependent Poisson SCCS model with 365-day age bands, plus nonparametric spline-based SCCS, sensitivity analyses, and post-hoc analysis.

Limitations

  • Stated: a possible time lag may exist between developing dementia and formal clinical diagnosis; the authors argue that extracting diagnoses from electronic medical records is the most feasible approach and that such a lag would not contradict their conclusions.
  • Stated: standard SCCS requires nonoverlapping segments, and 71 patients were excluded because washout and subsequent antidepressant exposure overlapped; the authors also note spline-based SCCS is underutilized.
  • Evident: the observational SCCS design cannot prove causality; findings rely on ICD-9-CM diagnosis codes and prescription records, use a three-year observation period with arbitrary 50-day pre-exposure and washout windows (though sensitivity-tested), and draw on Hong Kong public hospital data covering approximately 80% of hospital admissions, which may limit generalizability.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3233/jad-200875

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

6 of 30 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Interpretationown data
    § DISCUSSION

    The study's results do not support a causal association between antidepressant treatment and the risk of being diagnosed with dementia.

    “However, our results do not support earlier conclusions [5-8] that a causal association between antidepressant treatment and the development of dementia may exist (i.e. antidepressant drugs may increase the risk of dementia).”
    • Also stated in: § CONCLUSIONS · plain
      “Therefore, the findings of this pharmacoepidemiologic study do not support a causal association between antidepressant treatment and the risk of being diagnosed with dementia.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [5] [5] Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J (2019) Anticholinergic Drug Exposure and the Risk of Dementia: A Nested CaseControl Study. JAMA Intern. Med. 179, 1084-1093. -
    • cites [6] [6] Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB (2015) Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern. Med. 175, 401-407. - source

      The statement that “our results do not support” a causal association is the citing authors’ conclusion, not one attributed to Gray et al. Gray et al.’s Results report elevated dementia risk with heavy use of strong anticholinergic antidepressants, and the Discussion says the association does not appear to be explained by treatment of prodromal depression. This supports the cited possibility of a link, but not its extension to antidepressant treatment generally or a demonstrated causal effect. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [7] [7] Lee CWS, Lin CL, Sung FC, Liang JA, Kao CH (2016) Antidepressant treatment and risk of dementia: A population-based, retrospective case-control study. J. Clin. Psychiatry 77, 117-122. -
    • cites [8] [8] Heath LM, Gray SL, Boudreau D, Edwards KL, Fullerton SM, Thummel K, Larson EB (2016) Common Antidepressant Medications and Risk of Dementia: a Prospective Cohort Study. Alzheimer's Dement. 12, P1135-P1135. - source
  • Premisecitation
    § INTRODUCTION

    Approximately 50% of antidepressants are prescribed for other conditions, such as off-label indications for schizophrenia, insomnia, or incontinence.

    “It has been reported that approximately 50% of antidepressants are prescribed for other conditions (such as off-label indications for prescription e.g. schizophrenia, insomnia or incontinence) [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] [11] Moraros J, Nwankwo C, Patten SB, Mousseau DD (2017) The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis. Depress. Anxiety 34, 217-226. - source

      The Introduction (page unavailable) says almost half of antidepressant prescriptions are for off-label indications and lists insomnia as an example. It lists anxiety and pain, however, not the citing sentence’s examples of schizophrenia and incontinence. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation
    § DISCUSSION

    Earlier studies reporting a potential causal relationship between antidepressant drugs and the risk of being diagnosed with dementia controlled for none or only part of depression-related disorders.

    “Earlier studies [5-8] reporting a potential causal-relationship between antidepressant drugs and the risk of being diagnosed with dementia controlled for none or only part of depression-related disorders.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [5] [5] Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J (2019) Anticholinergic Drug Exposure and the Risk of Dementia: A Nested CaseControl Study. JAMA Intern. Med. 179, 1084-1093. -
    • cites [6] [6] Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB (2015) Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern. Med. 175, 401-407. - source

      The Methods (Covariates; Statistical Analyses) say the study adjusted for high depressive symptoms and, in a sensitivity analysis, recent rather than historical symptoms. The Results report elevated dementia risk for the anticholinergic-antidepressant subgroup, but the paper studies strong anticholinergic medications, not antidepressant drugs generally. Its adjustments therefore support the claim only for this narrower drug class and the depression measures described. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [7] [7] Lee CWS, Lin CL, Sung FC, Liang JA, Kao CH (2016) Antidepressant treatment and risk of dementia: A population-based, retrospective case-control study. J. Clin. Psychiatry 77, 117-122. -
    • cites [8] [8] Heath LM, Gray SL, Boudreau D, Edwards KL, Fullerton SM, Thummel K, Larson EB (2016) Common Antidepressant Medications and Risk of Dementia: a Prospective Cohort Study. Alzheimer's Dement. 12, P1135-P1135. - source
  • Findingown data
    § ##########Figure 4

    The mean (SD) time interval between two dementia diagnoses in the whole population was 114.14 (157.27) days.

    “The mean (SD) of the time interval between two dementia diagnoses in the whole population was 114.14 (157.27) days.”
    Quote in the paperSubstantial claim
  • Findingown data
    § ############Table 3

    The risk pattern from the spline-based SCCS is consistent with the results from the standard SCCS analysis.

    “The risk pattern is consistent with the results from the standard SCCS analysis.”
    Quote in the paperNot a substantial claim
  • It may state two separate claims as one. 9
  • Probably not a substantial claim. 17
  • The quote only partly states this claim. 6

  • It may state two separate claims as one.

    Study design and conductcitation
    § DATA SOURCE

    The HKHA electronic health records have been validated and previously used for investigations of medication safety.

    “The HKHA electronic health records have been validated, and previously used for investigations of medication safety [16-21].”
    Quote in the paperNot a substantial claim1 of 6 sources checked
    • cites [16] [16] Man KKC, Coghill D, Chan EW, Lau WCY, Hollis C, Liddle E, Banaschewski T, McCarthy S, Neubert A, Sayal K, Ip P, Schuemie MJ, Sturkenboom MCJM, SonugaBarke E, Buitelaar J, Carucci S, Zuddas A, Kovshoff H, Garas P, Nagy P, Inglis SK, Konrad K, Häge A, Rosenthal E, Wong ICK (2017) Association of risk of suicide attempts with methylphenidate treatment. JAMA Psychiatry 74, 1048-1055. -
    • cites [17] [17] Man KKC, Coghill D, Chan EW, Lau WCY, Hollis C, Liddle E, Banaschewski T, Mccarthy S, Neubert A (2016) Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Transl. Psychiatry 6, e956-e956. -
    • cites [18] [18] Man, K; Lau, WCY; Coghill, D; Besag, FMC; Cross, JH; Ip, P; Wong I (2020) Association between methylphenidate treatment and risk of seizure: A population-based self-controlled case series study. Lancet Child Adolesc. Heal. 4, 435-443. - source
    • cites [19] [19] Chui CSL, Man KKC, Cheng C, Chan EW, Lau WCY, Cheng VCC, Wong DSH, Kao YY, Wong ICK (2014) An investigation of the potential association between retinal detachment and oral fluoroquinolones: a self-controlled case series study. 69, 2563-2567. -
    • cites [20] [20] Wong AYS, Root A, Douglas IJ, Chui CSL, Chan EW, Ghebremichael-weldeselassie Y, Siu C, Smeeth L, Wong ICK (2016) Cardiovascular outcomes associated with use of clarithromycin : population based study. Bmj 352, h6926. -
    • cites [21] [21] Lau WCY, Chan EW, Cheung CL, Sing CW, Man KKC, Lip GYH, Siu CW, Lam JKY, Lee ACH, Wong ICK (2017) Association between Dabigatran vs Warfarin and risk of osteoporotic fractures among patients with nonvalvular atrial fibrillation. JAMA - J. Am. Med. Assoc. 317, 1151-1158. -

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation
    § DISCUSSION

    The SCCS approach has been successfully applied in other epidemiological studies, including studies of herpes zoster and stroke, and methylphenidate treatment with suicide attempts, psychosis, and seizures.

    “This approach has been successfully applied in other epidemiological studies which, for example, explore the association between herpes zoster and stroke [37], or the association between methylphenidate treatment with suicide attempts [16], psychosis [17] and seizures [18].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [37] [37] Langan SM, Minassian C, Smeeth L, Thomas SL (2014) Risk of stroke following herpes zoster: A self-controlled case-series study. Clin. Infect. Dis. 58, 1497-1503. - source
    • cites [16] [16] Man KKC, Coghill D, Chan EW, Lau WCY, Hollis C, Liddle E, Banaschewski T, McCarthy S, Neubert A, Sayal K, Ip P, Schuemie MJ, Sturkenboom MCJM, SonugaBarke E, Buitelaar J, Carucci S, Zuddas A, Kovshoff H, Garas P, Nagy P, Inglis SK, Konrad K, Häge A, Rosenthal E, Wong ICK (2017) Association of risk of suicide attempts with methylphenidate treatment. JAMA Psychiatry 74, 1048-1055. -
    • cites [17] [17] Man KKC, Coghill D, Chan EW, Lau WCY, Hollis C, Liddle E, Banaschewski T, Mccarthy S, Neubert A (2016) Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Transl. Psychiatry 6, e956-e956. -

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation
    § DISCUSSION

    The spline-based SCCS uses splines to smooth the exposure effect.

    “The splinebased SCCS [27,39] use splines to smooth the exposure effect.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [27] [27] Ghebremichael-Weldeselassie Y, Whitaker HJ, Farrington CP (2016) Flexible modelling of vaccine effect in self-controlled case series models. Biometrical J. 58, 607-622. -

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [39] [39] Ghebremichael-Weldeselassie Y, Whitaker HJ, Farrington CP (2017) Splinebased self-controlled case series method. Stat. Med. 36, 3022-3038. Table 1. Characteristics of participants. Table 2. CIRs of dementia being diagnosed in different periods. Table 3. Results of the standard SCCS analysis Table 4. Sensitivity analysis restricting to patients taking TCAs (No. of patients = 987) Table 5. Sensitivity analysis restricting to patients taking SSRIs (No. of patients = 1338) Table 6. Sensitivity analysis restricting to patients taking other antidepressant drugs (No. of patients = 300) Figure 1. source

  • It may state two separate claims as one.

    Findingown data
    § ############Table 3

    The nonparametric spline-based SCCS showed that the risk of developing dementia increased significantly before the initiation of antidepressant treatment and peaked within 50 days before treatment.

    “Subsequent analysis using the nonparametric, spline-based SCCS demonstrated that the risk of developing dementia increased significantly before the initiation of antidepressant treatment, and peaked within 50 days before treatment (Figure 3).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data
    § ##########Figure 2

    The IRR during the washout period was 1.12 (95% CI 0.77-1.36), similar to baseline.

    “The IRR during the washout period was 1.12 (95% CI: 0.77-1.36) (similar to baseline).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis setting the length of pre-exposure period to 70 days, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.16 (95% CI 0.79-1.40).

    “| Washout period | 1.16 (0.79-1.40) | <0.1 |”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis in women, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.14 (95% CI 0.82-1.54).

    “| Washout period | 1.14 (0.82-1.54) | <0.05 |”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis excluding any individual with drug duration <30, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 0.96 (95% CI 0.69-1.37).

    “| Washout period | 0.96 (0.69-1.37) | <0.1 |”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis setting the length of pre-exposure period to 30 days, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.08 (95% CI 0.84-1.40).

    “| Washout period | 1.08 (0.84-1.40) | <0.1 |”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis using 200-day age bands, the incidence rate ratio of dementia diagnosis during the index drug-exposed period compared with the baseline period was 8.88 (95% CI 7.82-10.09).

    “| Index drug-exposed period | 8.88 (7.82-10.09) | <0.001 |”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis using 500-day age bands, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.13 (95% CI 0.87-1.47).

    “| Washout period | 1.13 (0.87-1.47) | <0.1 |”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis setting the length of washout period to 70 days, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.15 (95% CI 0.83-1.34).

    “| Washout period | 1.15 (0.83-1.34) | <0.1 |”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis in men, the incidence rate ratio of dementia diagnosis during the index drug-exposed period compared with the baseline period was 9.84 (95% CI 7.93-12.20).

    “| Index drug-exposed period | 9.84 (7.93-12.20) | <0.001 |”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis in men, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.06 (95% CI 0.71-1.64).

    “| Washout period | 1.06 (0.71-1.64) | <0.1 |”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis in women, the incidence rate ratio of dementia diagnosis during the index drug-exposed period compared with the baseline period was 8.42 (95% CI 7.19-9.87).

    “| Index drug-exposed period | 8.42 (7.19-9.87) | <0.001 |”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § Supplementary materials of the manuscript entitled

    In the sensitivity analysis using 200-day age bands, the incidence rate ratio of dementia diagnosis during the washout period compared with the baseline period was 1.13 (95% CI 0.88-1.47).

    “| Washout period | 1.13 (0.88-1.47) | <0.1 |”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationreasoning
    § DISCUSSION

    Lack of information on relevant diagnoses may bias findings and lead to concerns about unmeasured confounders.

    “This may well bias findings, and lead to concerns about unmeasured confounders.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductcitation
    § MAIN ANALYSIS

    The age-adjusted IRR was calculated in the standard SCCS analysis by modeling dementia diagnoses within individuals as a non-homogeneous, age-dependent Poisson process and contrasting incident rates within the same individual's person-time, using age in 365-day bands.

    “The ageadjusted Incident Rate Ratio (IRR) was calculated in the standard SCCS analysis by modeling dementia diagnoses within individuals as a non-homogeneous, agedependent Poisson process and contrasting incident rates within the same individual's person-time [25], using age in 365-day bands.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] [25] Whitaker HJ, Farrington CP, Spiessens B, Musonda P (2006) Tutorial in biostatistics: The self-controlled case series method. Stat. Med. 25, 17681797. - source

  • It may state two separate claims as one.

    Study design and conductown data
    § ##########Figure 3

    The analyses for each antidepressant subcategory, each gender, and the additional sensitivity analyses were consistent with the main results.

    “The analyses for each subcategory (Table 4-6), each gender (Table S3-S4), and the additional sensitivity analyses (supplementary Table S5-S12), are consistent with the main results”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisenone given
    § DISCUSSION

    The SCCS design eliminates all time-invariant confounders among individuals, including mental disorders, and introduces temporal awareness around the event of interest.

    “We propose that an SCCS design may be a better way of examining whether an exposure truly represents a risk factor for an event because the design eliminates all time-invariant confounders among individuals (including mental disorders) and introduces temporal awareness around the event of interest.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data
    § DISCUSSION

    The observed increased risk of developing dementia before antidepressant treatment is not due to antidepressant treatment but precedes it, possibly reflecting emerging psychiatric symptoms or comorbid depressive complications that lead to medical consultation and a decision to prescribe antidepressants.

    “A possible explanation for such a risk pattern is that the observed increased risk of developing dementia is not due to antidepressant treatment but in fact precedes it, perhaps reflecting changes in comorbid depressive complications and/or associated impairment that lead to a medical consultation, which in turn may contribute to the decision to prescribe antidepressant drugs;”
    • Also stated in: § CONCLUSIONS · hedged
      “The observed higher risk of dementia before the commencement of antidepressant treatment may reflect emerging psychiatric symptoms, which can co-occur with dementia. These symptoms could trigger medical consultations where a decision is made to begin antidepressant treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductcitation
    § SELECTION CRITERIA INCLUSION CRITERIA

    The method of identifying people with dementia is consistent with previous studies.

    “This method of identifying people with dementia is consistent with previous studies [22,23].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] [22] Rose E, Glymour MM, Quesenberry CP, Whitmer RA (2016) Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimer's Dement. 12, 216-224. -
    • cites [23] [23] Gilsanz P, Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA (2017) Association Between Birth in a High Stroke Mortality State, Race, and Risk of Dementia. JAMA Neurol. 74, 1056-1062. - source

  • It may state two separate claims as one.

    Interpretationown data
    § DISCUSSION

    Depression-related disorders may be closely associated with dementia and should be strictly controlled in correlation models for prescription of antidepressant drugs and the development of dementia.

    “This indicates that depression-related disorders may be closely associated with dementia and this should be strictly controlled in correlation models for prescription of antidepressant drugs and the development of dementia.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper may give no reason why it holds.

    Interpretationnone given
    § DISCUSSION

    If there was a time lag between developing dementia and its diagnosis, this will not contradict the study's conclusions.

    “More importantly, in this study, if there was a time lag between developing dementia and its diagnosis, this will not contradict our conclusions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Study design and conductcitation
    § EXCLUSION CRITERIA

    Excluding subjects whose antidepressant drug exposure was shorter than seven days eliminated the impact of potentially ineffective exposures.

    “Potential subjects were excluded if (a) their antidepressant drug-exposure was shorter than seven days (to eliminate the impact of potentially-ineffective exposures) and/or (b) the washout period and subsequent exposure to antidepressants overlapped (thus violating model assumptions) [25].”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.

    Study design and conductreasoning
    § DISCUSSION

    We excluded 71 individuals whose washout period and subsequent antidepressant use overlapped to fulfill the SCCS model assumption.

    “We attempted to exclude these individuals (71) to fulfill the SCCS model assumption;”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper may give no reason why it holds.

    Premisenone given
    § DISCUSSION

    Standard SCCS only accepts nonoverlapping segments.

    “Standard SCCS only accepts nonoverlapping segments, whereas some studies may not ensure this.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

    Study design and conductnone given
    § DISCUSSION

    A possible time lag between the time of developing dementia and the time of a formal clinical diagnosis of dementia may exist.

    “For example, a possible time lag between the time of developing dementia and the time of a formal clinical diagnosis of dementia may exist.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Study design and conductcitation
    § EXCLUSION CRITERIA

    Excluding subjects whose washout period and subsequent exposure to antidepressants overlapped ensured the SCCS model assumptions were met.

    “Potential subjects were excluded if (a) their antidepressant drug-exposure was shorter than seven days (to eliminate the impact of potentially-ineffective exposures) and/or (b) the washout period and subsequent exposure to antidepressants overlapped (thus violating model assumptions) [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] [25] Whitaker HJ, Farrington CP, Spiessens B, Musonda P (2006) Tutorial in biostatistics: The self-controlled case series method. Stat. Med. 25, 17681797. - source
29 of 29

  • The authors state this as an assumption.

    The index dementia event was correctly identified as occurring during the study period.

    “This assumed that the index dementia event was correctly identified as occurring during the study period.”
1 of 1

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.

  • Table 6 reports significance despite an interval crossing baseline

    Major

    For subsequent exposure to other antidepressants, the reported 95% confidence interval of 0.78-8.53 includes the baseline IRR of 1. That conflicts with the reported P-value below 0.01.

  • MAOIs are assigned two different BNF codes

    Minor

    The discussion labels MAOIs as BNF 4.3.3, whereas the methods identify MAOIs as BNF 4.3.2.

  • Table S9 washout P-value conflicts with its confidence interval

    Minor

    The washout-period 95% confidence interval after excluding deaths includes the baseline IRR of 1, yet its P-value is reported as below 0.05.

  • Table S4 washout P-value conflicts with its confidence interval

    Minor

    The women's washout-period 95% confidence interval includes the baseline IRR of 1, yet its P-value is reported as below 0.05.

4 of 4

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Mielke, 2018, Sex and gender differences in Alzheimer disease dementia, Psychiatr Times, 35, 14

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Metadata

Authors
Xu, Z., Yang, J., Lau, K. K., Yip, P. S. F., Wong, I. C. K., & Zhang, Q.
Affiliations
  • City University of Hong Kong (HK)
  • University of Hong Kong (HK)
  • UCL School of Pharmacy (GB)
Corresponding author
  • Wong, Ian C.K.
  • Zhang, Qingpeng
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2020-11-10
Volume
78
Issue
2
Pages
735-744
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-200875
OpenAlex
W3089675543
Semantic Scholar
e0074b61e4d28b8a11d0f73280cb27bb94536fa4
Cited by
1
References
34
Citations by year
2023: 1
FWCI
0.17
Type
journal article
Language
en
Open access
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Natural Science Foundation of China (71972164, 71672163)
  • Health and Medical Research Fund (16171991)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
antidepressants, dementia
MeSH terms
Aged, Aged, 80 and over, Antidepressive Agents, Dementia, Female, Hong Kong, Humans, Male, Risk Factors, Cohort Studies, Case-Control Studies, Electronic Health Records

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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