Exposure to Antidepressant Medication and the Risk of Incident Dementia

Kodesh, Arad; Sandin, Sven; Reichenberg, Abraham; Rotstein, Anat; Pedersen, Nancy L.; Ericsson, Malin; Karlsson, Ida; Davidson, Michael; Levine, Stephen Z.

doi:10.1016/j.jagp.2019.05.019

Cited by 42 publications

(34 citation statements)

References 36 publications

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“…APOE e4 status was included as a potential confounder because it is a known predictor of dementia (outcome of interest) [36], while at the same time, there has also been reports of its association with NPS (exposure of interest) [37]. Similarly, antidepressant has been reported to be associated with dementia (outcome of interest) [38,39], and its use may potentially also modify the manifestation of NPS (exposure of interest). The primary analysis was based on participants with follow-up data beyond the baseline visits (also known as complete case analysis).…”

Section: Statistical Analysesmentioning

confidence: 99%

Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer’s and non-Alzheimer’s dementia

Liew

2020

Alz Res Therapy

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Background: Neuropsychiatric symptoms (NPS) have been reported to be useful in predicting incident dementia among cognitively normal older persons. However, the literature has not been conclusive on the differential utilities of the various NPS in predicting the subtypes of dementia. This study compared the risks of Alzheimer's and non-Alzheimer's dementia associated with the various NPS, among cognitively normal older persons. Methods: This cohort study included 12,452 participants from the Alzheimer's Disease Centers across USA, who were ≥ 60 years and had normal cognition at baseline. Participants completed the Neuropsychiatric Inventory-Questionnaire at baseline and were followed up almost annually for incident dementia (median follow-up = 4.7 years). Symptom clusters of NPS-as identified from exploratory and confirmatory factor-analyses-were included in the Cox regression to investigate their associations with incident dementia. Results: The various NPS showed independent yet differential associations with incident dementia. Although psychotic symptoms were rarely endorsed by the participants, they predicted much higher risk of dementia (HR 3.6, 95% CI 2.0-6.4) than affective symptoms (HR 1.5, 95% CI 1.2-1.8) or agitation symptoms (HR 1.6, 95% CI 1.3-2.1). Psychotic symptoms predicted all dementia subtypes, while affective and agitation symptoms differentially predicted some subtypes. Across dementia subtypes, psychotic symptoms had relatively higher risk estimates than affective or agitation symptoms, with the risk estimates being particularly high in non-Alzheimer's dementia. Conclusions: Among cognitively normal individuals, the presence of NPS may warrant greater clinical vigilance as precursors to dementia and its subtypes. The findings highlight the need for further research to enrich our understanding on the neurobiological links between various NPS and dementia subtypes. They may also change the clinical approach in managing late-life psychotic symptoms, requiring a greater emphasis on dementia surveillance in the diagnostic criteria of late-life psychotic disorders.

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Section: Statistical Analysesmentioning

confidence: 99%

Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer’s and non-Alzheimer’s dementia

Liew

2020

Alz Res Therapy

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“…We have addressed strategies for researchers who choose to perform (or as a result of available data are driven to) hazards-based analyses. Several prior studies have used hazard-based analyses to examine the association between anti-depressant use and cognitive impairment or dementia [10][11][12]14,16]. Results are inconclusive; several studies found that antidepressant use is associated with increased risk of developing cognitive impairment and dementia [10][11][12]14], while another found that use was associated with a decreased risk of developing dementia [16].…”

Section: Discussionmentioning

confidence: 99%

“…Findings about associations between antidepressant use and subsequent cognitive impairment have been inconsistent. Several studies have suggested that antidepressant use is associated with increased risk of developing cognitive impairment and dementia [9][10][11][12][13][14]. Some studies have found an inverse relationship-that antidepressant use may decrease the risk of developing dementia [15][16].…”

Section: Introductionmentioning

confidence: 99%

Estimating associations between antidepressant use and incident mild cognitive impairment in older adults with depression

et al. 2020

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IntroductionPrevious studies have provided equivocal evidence of antidepressant use on subsequent cognitive impairment; this could be due to inconsistent modeling approaches. Our goals are methodological and clinical. We evaluate the impact of statistical modeling approaches on the associations between antidepressant use and risk of Mild Cognitive Impairment (MCI) in older adults with depression. Methods716 participants were enrolled. Our primary analysis employed a time-dependent Cox proportional hazards model. We also implemented two fixed-covariate proportional hazards models-one based on having ever used antidepressants during follow-up, and the other restricted to baseline use only. ResultsTreating antidepressant use as a time-varying covariate, we found no significant association with incident MCI (HR = 0.92, 95% CI: 0.70, 1.20). In contrast, when antidepressant use was treated as a fixed covariate, we observed a significant association between having ever used antidepressants and lower risk of MCI (HR = 0.40, 95% CI: 0.28, 0.56). However, in the baseline-use only model, the association was non-significant (HR = 0.84, 95% CI: 0.60, 1.17).

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“…This is in line with the growing evidence for this association from observational studies, 32 and is consistent with a large, matched, prospective cohort study that found that antidepressant monotherapy was associated with an over twofold increased dementia risk in those aged over 60 after adjusting for multiple confounders, including depression. 33 Poor antidepressant response has been reported to be indicative of an especially increased risk of dementia in patients with cognitive impairment, 34 and it is likely that a number of patients in our study were referred to secondary care following treatment failure because over half had been prescribed antidepressants prior to reaching the service. However, this is challenging to disentangle if the efficacy of antidepressants might generally be reduced in patients aged over 65, as suggested by a number of meta-analyses.…”

Section: Open Accessmentioning

confidence: 94%

Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care

et al. 2020

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ObjectivesDepression can be a prodromal feature or a risk factor for dementia. We aimed to investigate which clinical factors in patients with late-life depression are associated with a higher risk of developing dementia and a more rapid conversion.DesignRetrospective cohort study.SettingSouth London and Maudsley NHS Foundation Trust (SLaM) secondary mental healthcare services.ParticipantsThe SLaM Clinical Record Interactive Search was used to retrieve anonymised data on 3659 patients aged 65 years or older who had received a diagnosis of depression in mental health services and had been followed up for at least 3 months.Outcome measuresPredictors of development of incident dementia were investigated, including demographic factors, health status rated on the Health of the National Outcome scale for older people (HoNOS65+), depression recurrence and treatments including psychotropic drugs and cognitive behavioural therapy (CBT).ResultsIn total, 806 (22.0%) patients developed dementia over a mean follow-up time of 2.7 years. Significant predictors of receiving a dementia diagnosis in fully adjusted models and after accounting for multiple comparisons were older age (adjusted HR=1.04, 95% CI 1.03 to 1.06 per year difference from sample mean) and the HoNOS65+ subscale measuring cognitive problems (HR=4.72, 95% CI 3.67 to 6.06 for scores in the problematic range). Recurrent depressive disorder or past depression (HR=0.65, 95% CI 0.55 to 0.77) and the receipt of CBT (HR=0.73 95% CI 0.61 to 0.87) were associated with a lower dementia risk. Over time, hazards related to age increased and hazards related to cognitive problems decreased.ConclusionsIn older adults with depression, a higher risk of being subsequently diagnosed with dementia was predicted by higher age, new onset depression, severity of cognitive symptoms and not receiving CBT. Further exploration is needed to determine whether the latter risk factors are responsive to interventions.

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Exposure to Antidepressant Medication and the Risk of Incident Dementia

Cited by 42 publications

References 36 publications

Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer’s and non-Alzheimer’s dementia

Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer’s and non-Alzheimer’s dementia

Estimating associations between antidepressant use and incident mild cognitive impairment in older adults with depression

Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care

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