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Risk of head and traumatic brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease: a nationwide matched cohort study.

ABSTRACT: Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease.A matched cohort study was conducted by comparing new antidepressant users (n = 10,910) with two matched nonusers (n = 21,820) in the MEDALZ study cohort. The MEDALZ cohort includes all community-dwelling persons newly diagnosed with Alzheimer's disease between 2005 and 2011 in Finland. Incident antidepressant users were identified based on register-based dispensing data from the Prescription register with a 1-year washout period for antidepressant use. Nonusers were matched with users based on age, gender, and time since Alzheimer's disease diagnosis. The outcome events were defined as any head injuries and traumatic brain injuries based on diagnoses in Hospital Discharge and Causes of Death registers. Propensity score adjusted Cox proportional hazard models were utilized. Sensitivity analyses with case-crossover design were conducted. All registers are linkable with unique personal identification numbers assigned for each resident.Antidepressant use was associated with an increased risk of head injuries (age-adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49-3.06) during use and 2.43 (95% CI 2.06-2.35) during nonuse, adjusted hazard ratio (HR) 1.35, 95% CI 1.20-1.52) and traumatic brain injuries (age-adjusted event rate per 100 person-years 1.33 (95% CI 1.13-1.53) during use and 1.10 (95% CI 1.00-1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06-1.50). The risk was highest during the first 30 days of use (HR 1.71, 95% CI 1.10-2.66 for head injuries; HR 2.06, 95% CI 1.12-3.82 for traumatic brain injuries) and remained at an elevated level for head injuries for over 2 years of use. In case-crossover analyses, antidepressant use was consistently associated with a higher risk of head injuries.Antidepressant use was associated with an increased risk of the most severe outcomes, head and brain injuries, in persons with Alzheimer's disease. Antidepressant use should be carefully considered and the association confirmed in future studies.

SUBMITTER: Taipale H

PROVIDER: S-EPMC5540546 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:ImportanceIdentifying genes and proteins for cognitive resilience (ie, targets that may be associated with slowing or preventing cognitive decline regardless of the presence, number, or combination of common neuropathologic conditions) provides a complementary approach to developing novel therapeutics for the treatment and prevention of Alzheimer disease and related dementias.ObjectiveTo identify proteins associated with cognitive resilience via a proteome-wide association study of the human dorsolateral prefrontal cortex.Design, setting, and participantsThis study used data from 391 community-dwelling older persons who participated in the Religious Orders Study and the Rush Memory and Aging Project. The Religious Orders Study began enrollment January 1, 1994, and the Rush Memory and Aging Project began enrollment September 1, 1997, and data were collected and analyzed through October 23, 2019.ExposuresParticipants had undergone annual detailed clinical examinations, postmortem evaluations, and tandem mass tag proteomics analyses.Main outcomes and measuresThe outcome of cognitive resilience was defined as a longitudinal change in cognition over time after controlling for common age-related neuropathologic indices, including Alzheimer disease, Lewy bodies, transactive response DNA-binding protein 43, hippocampal sclerosis, infarcts, and vessel diseases. More than 8000 high abundance proteins were quantified from frozen dorsolateral prefrontal cortex tissue using tandem mass tag and liquid chromatography-mass spectrometry.ResultsThere were 391 participants (273 women); their mean (SD) age was 79.7 (6.7) years at baseline and 89.2 (6.5) years at death. Eight cortical proteins were identified in association with cognitive resilience: a higher level of NRN1 (estimate, 0.140; SE, 0.024; P = 7.35 × 10-9), ACTN4 (estimate, 0.321; SE, 0.065; P = 9.94 × 10-7), EPHX4 (estimate, 0.198; SE, 0.042; P = 2.13 × 10-6), RPH3A (estimate, 0.148; SE, 0.031; P = 2.58 × 10-6), SGTB (estimate, 0.211; SE, 0.045; P = 3.28 × 10-6), CPLX1 (estimate, 0.136; SE, 0.029; P = 4.06 × 10-6), and SH3GL1 (estimate, 0.179; SE, 0.039; P = 4.21 × 10-6) and a lower level of UBA1 (estimate, -0.366; SE, 0.076; P = 1.43 × 10-6) were associated with greater resilience.Conclusions and relevanceThese protein signals may represent novel targets for the maintenance of cognition in old age.

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Risk of head and traumatic brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease: a nationwide matched cohort study.

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