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Cited by 11Dementia and Cognitive Impairment ResearchTreatment of Major DepressionAlzheimer's disease research and treatments

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index; 9 of the 20 sources its claims cite were checked for support.

Antidepressant exposure and long‐term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder

Open access
Ramos‐Cejudo, Jaime, Corrigan, June K., Zheng, Chunlei, Swinnerton, Kaitlin N., Jacobson, Sean R., La, Jennifer, Betensky, Rebecca A., Osorio, Ricardo S., Madanes, Sharon, Pomara, Nunzio, Iosifescu, Dan, Brophy, Mary, Do, Nhan V., Fillmore, Nathanael R.·2024·Alzheimer's & Dementia
DOI 10.1002/alz.13853PMC PMC11180845
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Abstract

INTRODUCTION: The use of antidepressants in major depressive disorder (MDD) has been reported to influence long‐term risk of Alzheimer's disease (AD) and AD‐related dementias (AD/ADRD), but studies are conflicting. METHODS: We used inverse probability weighted (IPW) Cox models with time‐varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare system from January 1, 2000 to June 1, 2022. RESULTS: A total of 35,200 patients with MDD were identified. No associations were seen regarding the effect of being exposed to any antidepressant versus no exposure on AD/ADRD risk (events = 1,056, hazard ratio = 0.94, 95% confidence interval: 0.81 to 1.09) or the exposure to specific antidepressant classes versus no exposure. A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small. DISCUSSION: Our study suggests that antidepressant exposure has no effect on AD/ADRD risk. The association in female patients should be interpreted with caution and requires further attention. Highlights: We studied whether antidepressant use was associated with future dementia risk. We specifically focused on patients after their first‐ever diagnosis of depression. We used IPW Cox models with time‐varying covariates and a large observation window. Our study did not identify an effect of antidepressant use on dementia risk. A risk reduction was observed in female patients, but the number of cases was small.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a nationwide retrospective cohort of 35,200 US veterans with midlife major depressive disorder, antidepressant exposure was not associated with incident Alzheimer’s disease and related dementias. A possible risk reduction was seen in female patients, but the authors caution it was based on a small number of cases.

Key findings

  • Among 35,200 patients with MDD (mean age 65.4 years; 90.6% male), 16,815 (47.8%) received antidepressant treatment; 1,056 (3%) received a dementia diagnosis, and 1,944 (5.5%) died before dementia diagnosis.
  • Overall antidepressant exposure versus no exposure was not associated with AD/ADRD risk: the abstract reports HR = 0.94, 95% CI 0.81–1.09, while Table 2 reports aHR = 0.93, 95% CI 0.80–1.08, p = 0.32.
  • No individual antidepressant class showed a significant association: SSRI events = 937, HR = 0.92, 95% CI 0.78–1.08; NDRI events = 524, HR = 0.81, 95% CI 0.43–1.50; SNRI events = 547, HR = 0.87, 95% CI 0.54–1.42; NaSSA events = 527, HR = 0.89, 95% CI 0.50–1.59. TCA HR could not be estimated due to few events.
  • In a sex-stratified analysis, female patients showed reduced AD/ADRD risk with antidepressant exposure (events = 30, HR = 0.29, 95% CI 0.12–0.75, p = 0.01), but the authors state the number of cases was small; no significant association was observed in males.

Methods

  • Retrospective cohort study using US Department of Veterans Affairs Corporate Data Warehouse electronic health records from January 1, 2000 to June 1, 2022; inclusion required veteran status, MDD defined by at least two ICD codes at least one year apart, at least one year of prior VA encounters, no dementia before MDD diagnosis or treatment initiation, and continuous VHA usage.
  • Antidepressant exposure was defined from pharmacy data using OMOP drug-era periods and required a prescription lasting over 3 months; exposure and covariates were updated monthly in time-varying models, with death treated as a competing risk.
  • Primary analysis used inverse probability weighted Cox proportional hazards models with time-varying covariates, adjusted for age, sex, race, ethnicity, obesity, diabetes, hypertension, smoking, peripheral artery disease, coronary artery disease, traumatic brain injury, neurodegenerative disorder, bipolar disorder, PTSD, psychotic MDD subtype, and benzodiazepine use; sensitivity analyses used age cutoffs of 60 and 65 and 5-year follow-up intervals.

Limitations

  • The authors state the cohort was relatively young, limiting the number of dementia cases during follow-up; supplemental insurance data such as Medicare after age 65 were not included, potentially limiting capture of dementia and death outcomes; MDD and AD/ADRD were defined by ICD codes, which have imperfect sensitivity and specificity; antidepressant combinations were not examined; and the female subgroup finding was limited by small sample size.
  • The text makes evident that the cohort was overwhelmingly male (90.6%), so the sex-stratified female result is based on very few events and cannot be generalized; median follow-up was only 3.2 years despite the 22-year observation window.
  • The paper reports slightly different overall hazard ratios in the abstract (HR = 0.94, 95% CI 0.81–1.09) and Table 2 (aHR = 0.93, 95% CI 0.80–1.08), an inconsistency evident in the text.

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

Integrity signals

Registry

Crossref · 10.1002/alz.13853

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

9 of 20 cited sources checked · 4 supported · 1 flagged · accuracy not yet measured

  • Study design and conductcitation
    § 4 DISCUSSION · p. 7

    The specific ICD-code-based definitions used for MDD and AD/ADRD were validated or used in multiple previous studies.

    “However, the specific ICD-codebased definitions we used were validated or used in multiple previous studies for MDD 9 and AD/ADRD. 12-14”
    Quote in the paperNot a substantial claim4 of 4 sources checked
    • cites [9] 9. Doktorchik C, Patten S, Eastwood C, et al. Validation of a case definition for depression in administrative data against primary chart data as a reference standard. BMCPsychiatry . 2019;19:9. doi:10.1186/ s12888-018-1990-6 source

      The Methods section lists ICD-9-CM and ICD-10 codes used to define depression, and the Results section validates an administrative-data case definition against physician charts. The paper does not validate a definition specific to major depressive disorder (MDD), and the citing sentence does not provide its exact codes for comparison. The AD/ADRD portion is attributed to other citations, not this paper. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [12] 12. Cheng Y, Ahmed A, Zamrini E, Tsuang DW, Sheriff HM, Zeng-Treitler Q. Alzheimer's Disease and Alzheimer's disease-related dementias in older African American and white veterans. J Alzheimers Dis . 2020;75:311-320. doi:10.3233/JAD-191188 source
    • cites [13] 13. Logue MW, Miller MW, Sherva R, et al. Alzheimer's disease and related dementias among aging veterans: examining gene-byenvironment interactions with post-traumatic stress disorder and traumatic brain injury. Alzheimers Dement . 2023;19:2549-2559. doi:10.1002/alz.12870 source
    • cites [14] 14. Jutkowitz E, Halladay C, Tsai J, et al. Prevalence of Alzheimer's disease and related dementias among veterans experiencing housing insecurity. Alzheimers Dement . 2022;18:1306-1313. doi:10.1002/alz. 12476 source
  • Premisecitation
    § 1 INTRODUCTION · p. 2

    Studies investigating the relationship between antidepressant use and AD/ADRD risk have yielded conflicting results.

    “Studies looking into this question, however, have yielded conflicting results. 4-7”
    • Also stated in: § Abstract · p. 1 · plain
      “The use of antidepressants in major depressive disorder (MDD) has been reported to influence long-term risk of Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), but studies are conflicting.”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [4] 4. Kessing LV, Forman JL, Andersen PK. Do continued antidepressants protect against dementia in patients with severe depressive disorder? Int Clin Psychopharmacol . 2011;26:316-322. doi:10.1097/YIC. 0b013e32834ace0f source
    • cites [5] 5. Deví Bastida J, Puig Pomés N, Jofre Font S, Fetscher Eickhoff A. La depresión: un predictor de demencia. Revista Española de Geriatría y Gerontología . 2016;51:112-118. doi:10.1016/j.regg.2015.10.008 source
    • cites [6] 6. Wang YC, Tai PA, Poly TN, et al. Increased risk of dementia in patients with antidepressants: a meta-analysis of observational studies. Behav Neurol . 2018;2018:5315098. doi:10.1155/2018/5315098 source
    • cites [7] 7. Jones HE, Joshi A, Shenkin S, Mead GE. The effect of treatment with selective serotonin reuptake inhibitors in comparison to placebo in the progression of dementia: a systematic review and meta-analysis. Age Ageing . 2016;45:448-456. doi:10.1093/ageing/afw053 source

      The Background (page unavailable) describes mixed findings on whether SSRIs affect cognition in people who already have dementia. The Abstract likewise concerns SSRI treatment after a dementia diagnosis. Neither passage addresses whether antidepressant use is associated with the risk of developing AD or related dementias; searches for that risk and for conflicting results found no such discussion. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Premisecitation
    § 1 INTRODUCTION · p. 2

    Major depressive disorder (or depression) is a risk factor for dementia.

    “Another challenge is that depression is itself a risk factor for dementia, and studies need to appropriately consider this aspect when looking at the effects of antidepressant exposure.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] 1. Green RC, Cupples LA, Kurz A, et al. Depression as a risk factor for Alzheimer disease: the MIRAGE study. Arch Neurol . 2003;60:753-759. doi:10.1001/archneur.60.5.753 source
    • cites [2] 2. Byers AL, Yaffe K. Depression and risk of developing dementia. NatRev Neurol . 2011;7:323-331. doi:10.1038/nrneurol.2011.60 source

      The Earlier-life depression and dementia risk section says earlier-life depression has consistently been studied as a risk factor and is unlikely to be a prodrome. But the Treatment and management implications section says research has not resolved whether depression more generally is a prodrome or a risk factor. The unqualified claim omits that distinction. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingown data
    § Abstract · p. 1

    A total of 35,200 patients with MDD were identified in the national VA healthcare system between January 1, 2000 and June 1, 2022.

    “A total of 35,200 patients with MDD were identified.”
    • Also stated in: § 3.1 Cohort characteristics · p. 4 · plain
      “We identified 35,200 patients diagnosed with MDD in the national VA healthcare system between January 1, 2000 and June 1, 2022 who were eligible according to our inclusion criteria (see Methods ).”
    Quote in the paperSubstantial claim
  • Findingown data
    § 3.2.1 Primary analysis · p. 5

    NaSSA exposure was not associated with AD/ADRD risk (events = 527, HR = 0.89, 95% CI: 0.50 to 1.59).

    “Similarly, current exposure to individual antidepressant drug classes was not associated with an effect on AD/ADRD risk (Selective serotonin reuptake inhibitors (SSRI), events = 937, HR = 0.92, 95%CI: 0.78 to 1.08; norepinephrine and dopamine reuptake inhibitor [NDRI], events = 524, HR = 0.81, 95% CI: 0.43 to 1.50; serotoninnorepinephrine reuptake inhibitor [SNRI], events = 547, HR = 0.87, 95% CI:”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim. 20
  • It may state two separate claims as one. 7

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

    Study design and conductcitation
    § 2.1 Study design and inclusion criteria · p. 2

    The MDD definition (at least two MDD-ICD codes at least a year apart) is aligned with prior recommendations for MDD studies using EHR data.

    “These criteria are aligned with prior recommendations for MDD studies using EHR data. 9”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] 9. Doktorchik C, Patten S, Eastwood C, et al. Validation of a case definition for depression in administrative data against primary chart data as a reference standard. BMCPsychiatry . 2019;19:9. doi:10.1186/ s12888-018-1990-6 source

      The Methods and Results define the preferred rule as two depression claims within a one-year window, or one hospital discharge diagnosis—not two ICD codes at least a year apart. The paper studies depression in administrative data and does not present the claimed rule as a recommendation for MDD studies using EHR data. Page numbers are not provided in our copy. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

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

    Study design and conductcitation
    § 2.4 Outcome · p. 3

    The AD/ADRD outcome definition (two or more ICD codes in a single year) is similar to those used in previously published studies using ICD-based dementia diagnosis.

    “Our definition is similar to those used in previously published studies using ICD-based dementia diagnosis. 12-14”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [12] 12. Cheng Y, Ahmed A, Zamrini E, Tsuang DW, Sheriff HM, Zeng-Treitler Q. Alzheimer's Disease and Alzheimer's disease-related dementias in older African American and white veterans. J Alzheimers Dis . 2020;75:311-320. doi:10.3233/JAD-191188

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

    • cites [13] 13. Logue MW, Miller MW, Sherva R, et al. Alzheimer's disease and related dementias among aging veterans: examining gene-byenvironment interactions with post-traumatic stress disorder and traumatic brain injury. Alzheimers Dement . 2023;19:2549-2559. doi:10.1002/alz.12870

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

    • cites [14] 14. Jutkowitz E, Halladay C, Tsai J, et al. Prevalence of Alzheimer's disease and related dementias among veterans experiencing housing insecurity. Alzheimers Dement . 2022;18:1306-1313. doi:10.1002/alz. 12476 source

      The Methods section (page unavailable) confirms that this study used ICD-9/10 diagnosis codes to identify AD/ADRD, so it is an example of an ICD-based dementia definition. It evaluated whether a veteran ever had a qualifying code between 2016 and 2018; our copy does not support the more specific definition of two or more codes in a single year. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Findingown data
    § 3.2.1 Primary analysis · p. 5

    In the final sample, 1,056 patients received a dementia diagnosis, representing 3% of the cohort (0.9% female).

    “A total of 1,056 received a dementia diagnosis, representing 3% of the cohort (0.9% female).”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § 3.2.1 Primary analysis · p. 5

    Median follow-up time in the overall cohort was 3.2 years [Q1, Q3: 3.2, 3.3], 3.3 years [3.2, 3.3] for males, and 2.7 years [2.6, 2.9] for females.

    “Median follow-up time [Q1, Q3] in the overall cohort was 3.2 years [3.2, 3.3], 3.3 years [3.2, 3.3] for males, and 2.7 [2.6, 2.9] for females.”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § 3.2.2 Sensitivity analysis · p. 5

    Median age at incident AD/ADRD diagnosis was 77.6 years in the 55+ cohort, 77.9 years in the 60+ cohort, and 79.4 years in the 65+ cohort among those diagnosed with AD/ADRD.

    “The median age at the time of incident AD/ADRD diagnosis was 77.6 years in the main 55 + cohort, 77.9 years in the 60 + cohort, and 79.4 years in the 65 + cohort among those who received a diagnosis of AD/ADRD.”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § 3.2.1 Primary analysis · p. 5

    In the final sample, 1,944 patients died before receiving a dementia diagnosis, representing 5.5% of the cohort (1.7% female).

    “From the final sample, 1,944 patients died before receiving a dementia diagnosis, representing 5.5% (1.7% female).”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data
    § Abstract · p. 1

    In a sex-stratified analysis, a risk reduction for AD/ADRD was observed among female patients exposed to antidepressants, but the number of cases was small.

    “A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small.”
    • Also stated in: § RESEARCHINCONTEXT · p. 3 · hedged
      “In subgroup analysis stratified by sex, a reduction in risk due to antidepressant exposure was suggested in female patients; however, the number of cases was small.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § 4 DISCUSSION · p. 7

    Some US veterans may use supplemental insurance, including Medicare after age 65, and the study did not include these data, potentially limiting capacity to capture dementia and death outcomes.

    “Additionally, some US veterans may make use of supplemental insurance, including Medicare after the age of 65, and our study did not include these data in its analysis, potentially limiting our capacity to capture dementia and death outcomes.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § 2.5.1 Primary analysis · p. 3

    The proportional hazards assumption was validated graphically using Kaplan-Meier.

    “The proportional hazards assumption was validated graphically using Kaplan-Meier (KM).”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning
    § 4 DISCUSSION · p. 7

    The study attempted to address the limitation of missing supplemental insurance data by requiring at least annual visits to a VA facility during follow-up.

    “We attempted to address this limitation by requiring at least annual visits to a VA facility during the follow-up period.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data
    § 2.3 Covariates · p. 3

    Adding age as a quadratic term did not substantially affect the adjusted hazard ratios.

    “Adding age as a quadratic term did not substantially affect the adjusted hazard ratios, and for simplicity, only age as a linear term was considered.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning
    § 2.5.2 Sensitivity analyses · p. 4

    An additional sensitivity analysis split follow-up time into 5-year intervals to avoid potential reverse causation.

    “To avoid the risk of potential reverse causation, an additional sensitivity analysis was done by splitting follow-up time into 5-year intervals.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Premisecitation
    § 4 DISCUSSION · p. 6

    Several systematic reviews and meta-analyses have indicated that antidepressant use is associated with an increased risk of dementia.

    “Several systematic reviews and meta-analyses on the topic have also indicated that antidepressant use is associated with an increased risk of dementia. 6,20-22”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [6] 6. Wang YC, Tai PA, Poly TN, et al. Increased risk of dementia in patients with antidepressants: a meta-analysis of observational studies. Behav Neurol . 2018;2018:5315098. doi:10.1155/2018/5315098

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

    • cites [20] 20. Wang GH, Li P, Wang Y, Guo J, Wilson DL, Lo-Ciganic WH. Association between antidepressants and dementia risk in older adults with depression: a systematic review and meta-analysis. J Clin Med . 2023;12:6342. doi:10.3390/jcm12196342

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

    • cites [21] 21. Moraros J, Nwankwo C, Patten SB, Mousseau DD. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: a systematic review and meta-analysis. Depress Anxiety . 2017;34:217-226. doi:10.1002/da.22584

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

    • cites [22] 22. Chan JYC, Yiu KKL, Kwok TCY, Wong SYS, Tsoi KKF. Depression and antidepressants as potential risk factors in dementia: a systematic review and meta-analysis of 18 longitudinal studies. J Am Med Dir Assoc . 2019;20:279-286 e271. doi:10.1016/j.jamda.2018.12.004

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

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

    Premisereasoning
    § 4 DISCUSSION · p. 6

    Previous literature on antidepressant exposure and dementia risk has produced conflicting results due to differences in study design.

    “Due to differences in study design, previous literature in this topic produced conflicting results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Study design and conductnone given
    § 4 DISCUSSION · p. 6

    The large nationwide VA database allowed evaluation of outcomes in a large population and over long follow-up times.

    “The large nationwide VA database allowed the evaluation of outcomes in a large population and over long follow-up times.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § 4 DISCUSSION · p. 7

    Previous research has reported potential sex differences in antidepressant response.

    “This is particularly significant considering previous research reported potential sex differences in antidepressant response. 31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31]

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

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

    Study design and conductreasoning
    § 4 DISCUSSION · p. 7

    All analyses were adjusted for race and ethnicity to address potential biases and ensure findings could be generalized across the veteran population.

    “To address potential biases and ensure that the findings could be generalized across the veteran population, all analyses were adjusted for race and ethnicity.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductnone given
    § 4 DISCUSSION · p. 7

    The study controlled for a large number of covariates while focusing on a relatively homogeneous cohort of midlife patients immediately after their first-ever diagnosis of MDD and fit time-varying models.

    “Our study, which controlled for a rather large number of covariates while focusing on a relatively homogeneous cohort of midlife patients immediately after their first-ever diagnosis of MDD and fit time-varying models, did not detect associations with drug exposure.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Patients in retrospective data often interrupt or switch treatments.

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

    Study design and conductnone given
    § 2.5.2 Sensitivity analyses · p. 4

    Sensitivity analyses used age cut-offs of 60 and 65 years.

    “Sensitivity analysis was done for subgroups using cut-offs of 60 and 65 years of age.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § 4 DISCUSSION · p. 7

    The study did not examine the effect of particular combinations of antidepressants on AD/ADRD risk.

    “A limitation of our study is also the fact that we did not examine the effect of particular combinations of antidepressants on AD/ADRDrisk.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning
    § 4 DISCUSSION · p. 7

    The higher exposure rate in the cohort (47.8%) is probably due to focusing on recurrent MDD and higher rates of associated psychiatric comorbidity such as PTSD, psychotic MDD, and benzodiazepine use.

    “In our cohort, 47.8% of those with MDD were identified as exposed, which is higher probably due to the fact that we focused on recurrent MDDand the higher rates of associated psychiatric comorbidity such as higher rates of PTSD, psychotic MDD, and a higher use of benzodiazepines.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductnone given
    § 5 CONCLUSION · p. 7

    The study was conducted in a large population with appropriate adjustment of confounders and used time-varying covariates for drug exposure.

    “Our study, which was conducted in a large population with appropriate adjustment of confounders and used time-varying covariates for drug exposure, did not find an association between antidepressant use and AD/ADRD risk.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Patients in retrospective data often interrupt or switch treatments.

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

    Premisecitation
    § 4 DISCUSSION · p. 7

    In the US, approximately 40% of females and 20% of males with depression use antidepressants, based on CDC data.

    “approximately 40% for females and 20% for males with depression in the US based on data from the Centers for Disease Control and Prevention (CDC). 30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] 30. Pratt LA, Brody DJ, Gu Q Antidepressant use in persons aged 12 and over: United States, 2011-2014. NCHS data brief, no 283. Hyattsville, MD:National Center for Health Statistics. 2011. <!-- image -->
23 of 23

  • The paper relies on this without support.

    Patients with MDD often switch antidepressant treatments during follow-up.

    “Because patients with MDD often switch antidepressant treatments, we used time-dependent covariates where antidepressant exposure was updated monthly throughout the study period.”
    “One of the challenges in retrospective studies is that MDD patients may interrupt or switch antidepressant treatments during the observation window.”

  • The paper relies on this without support.

    The VHA is the largest integrated healthcare system in the United States and provides medical services to over nine million patients each year, including populations typically underrepresented in clinical trials.

    “The VHA is the largest integratedhealthcaresystemintheUnitedStatesandprovidesmedical services to over nine million patients each year, including populations thataretypicallyunderrepresentedinclinicaltrials.”

  • The paper relies on this without support.

    In retrospective cohort studies without random assignment, unadjusted comparison between treatment groups may be misleading because of confounding and selection bias.

    “In retrospective cohort studies where there is no random assignment to treatment groups (eg, antidepressant exposure in our case), the unadjusted comparison between treatment groups may be misleading because of confounding and selection bias.”

  • The paper relies on this without support.

    The measured covariates are sufficient to control for confounding of the association between antidepressant exposure and AD/ADRD risk.

    “One method to adjust for these features using measured confounders is through IPW, which weights contributions to the model with the probability of falling in each of the treatment arms based on study covariates (listed above) and disease duration (defined as the days from MDD diagnosis to the baseline of each of the study periods (see below).”

  • The paper relies on this without support.

    ICD-code-based definitions have imperfect sensitivity and specificity.

    “Additionally,wedefinedMDDandAD/ADRDusingICD codes, and ICD-code-based definitions have well-known limitations of imperfect sensitivity and specificity.”

  • The paper relies on this without support.

    Patients in retrospective data often interrupt or switch treatments.

    “Oneofthe main difficulties when attempting to approach this question using retrospective data is that patients often interrupt or switch treatments.”
6 of 6

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?

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 2 defines SSRI inconsistently

    Minor

    Table 2 defines SSRI as a serotonin-norepinephrine reuptake inhibitor, whereas Table 1 defines it as a selective serotonin reuptake inhibitor. The Table 2 definition also duplicates its definition of SNRI.

1 of 1

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Metadata

Authors
Ramos‐Cejudo, J., Corrigan, J. K., Zheng, C., Swinnerton, K. N., Jacobson, S. R., La, J., Betensky, R. A., Osorio, R. S., Madanes, S., Pomara, N., Iosifescu, D., Brophy, M., Do, N. V., & Fillmore, N. R.
Affiliations
  • VA Boston Healthcare System (US)
  • Boston University (US)
  • New York University (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • Brigham and Women's Hospital (US)
Corresponding author
  • Ramos‐Cejudo, Jaime
  • Fillmore, Nathanael R.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2024-05-08
Volume
20
Issue
6
Pages
4106-4114
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.13853
PMC
PMC11180845
OpenAlex
W4396736540
Cited by
11
References
34
Citations by year
2026: 6 · 2025: 3 · 2024: 2
FWCI
2.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R01AG070821, R01AG079282)
  • National Alzheimer's Coordinating Center (AY2022/23)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
antidepressant exposure, dementia risk
MeSH terms
Aged, Antidepressive Agents, Dementia, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, United States, Veterans, Proportional Hazards Models

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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