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Letter to the Editor

Dr Cheng and Colleagues Reply

Chih-Ming Cheng, MDa,b,c,d; Mu-Hong Chen, MD, PhDa,b,c; Cheng-Hung Yang, MDa,b; Shih-Jen Tsai, MDa,b; and Chia-Fen Tsai, MD, PhDa,b,c

Published: March 24, 2020

See Letter by Modrego and article by Cheng et al

To the Editor: We thank Dr Modrego for the response to our article.1 We acknowledge that Drs Modrego and Lobo, in their systematic review,2 stated that there is still not enough evidence to conclude that a link exists between antipsychotic use and mortality in dementia patients. Confounding factors may limit the results of observational studies investigating this question, but randomized controlled trials may fail to reflect real-world clinical situations because of their inclusion and exclusion criteria.3 A similar limitation also exists for investigations of the association between antidepressant use and mortality in dementia patients. To date, findings regarding the impact of antidepressants on mortality in dementia patients have been inconsistent.1,4-6

On the other hand, the presence of behavioral and psychological symptoms of dementia (BPSD) may be a valuable factor in predicting mortality in dementia patients.2 For example, agitation and aggression may cause head trauma or fractures due to falls and therefore increase the risk of death.7 Lopez et al7 found that the increased risk of death in patients with probable Alzheimer’s disease was associated with the presence of psychiatric symptoms rather than exposure to antipsychotics. Our registry database, the National Health Insurance Research Database, did not provide information about BPSD or neuropsychiatric inventory results. Consequently, we could not evaluate the influence of these factors. However, the severity and type of BPSD may change over time.8 BPSD symptoms may elevate the risk of falls and fracture events, which were evaluated as the factor “femoral neck fracture” in our article.1

The proportions of patients with Alzheimer’s type dementia (ICD-9 code = 331.0) and vascular type dementia (ICD-9 code = 290.4) in the derivation cohort were 9.9% and 15.9%, respectively. We performed another analysis to add those factors of different dementia types into our Cox proportional hazards regression model, which was equal to the creating process described in our article.1 The results showed that neither Alzheimer’s type nor vascular type dementia was significant as a factor for the final variables selection (vascular type: P = .79, Alzheimer’s type: P = .974) compared with other predicting variables. This result was generally in accord with previous findings. In a brain neuropathology study, the authors found few dementia cases that did not have a mixed component of both Alzheimer’s -type pathologies and vascular lesions.9 According to the literature, although vascular dementia may be associated with a slightly higher mortality rate, the excess mortality in patients with certain stroke features may be driven greatly by cardiovascular disease outside the brain.10,11 Stroke or vascular dementia may demonstrate a phenomenon of worse generalized vascular disease that is not specific to the brain. More investigations will be required to clarify if type of dementia (especially vascular and Alzheimer’s type dementia) impacts significantly as an independent predictor in the prediction model with adjustment for comorbidity variables (ie, competing mortality risks).

Chih-Ming Cheng, MDa,b,c,d
Mu-Hong Chen, MD, PhDa,b,c
Cheng-Hung Yang, MDa,b
Shih-Jen Tsai, MDa,b
Chia-Fen Tsai, MD, PhDa,b,c

aDepartment of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
bDivision of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
cInstitute of Brain Science, National Yang-Ming University, Taipei, Taiwan
dDepartment of Psychiatry, Taipei Veterans General Hospital, Yuanshan Branch, Yilan, Taiwan

Published online: March 24, 2020.
Potential conflicts of interest: None.
Funding/support: The authors’ study discussed in this letter was supported by grants from Taipei Veterans General Hospital (V105D10-001-MY2-2), Ministry of Science and Technology (MOST 107-2634-F-075-002), and Taipei Veterans General Hospital-National Yang-Ming University Excellent Physician Scientists Cultivation Program (No.106-V-B-084).
Role of the sponsor: None of the supporters of the study had any role in the study design, data collection, analysis, interpretation of results, writing of the report, or the ultimate decision to submit the manuscript for publication.

J Clin Psychiatry 2020;81(3):19lr13217a

To cite: Cheng CM, Chen MH, Yang CH, et al. Dr Cheng and colleagues reply.
J Clin Psychiatry. 2020;81(3):19lr13217a.
To share:
© Copyright 2020 Physicians Postgraduate Press, Inc.


1.Cheng CM, Chang WH, Chiu YC, et al. Risk score for predicting mortality in people with dementia: a nationwide, population-based cohort study in Taiwan with 11 years of follow-up. J Clin Psychiatry. 2019;80(4):18m12629. PubMed CrossRef

2.Modrego PJ, Lobo A. Determinants of progression and mortality in Alzheimer’s disease: a systematic review. Neuropsychiatry (London). 2018;8(5):1465-1475.

3.Yeh TC, Tzeng NS, Li JC, et al. Mortality risk of atypical antipsychotics for behavioral and psychological symptoms of dementia: a meta-analysis, meta-regression, and trial sequential analysis of randomized controlled trials. J Clin Psychopharmacol. 2019;39(5):472-478. PubMed CrossRef

4.Su JA, Chang CC, Wang HM, et al. Antidepressant treatment and mortality risk in patients with dementia and depression: a nationwide population cohort study in Taiwan. Ther Adv Chronic Dis. 2019;10:2040622319853719. PubMed CrossRef

5.Mueller C, Huntley J, Stubbs B, et al. Associations of neuropsychiatric symptoms and antidepressant prescription with survival in Alzheimer’s disease. J Am Med Dir Assoc. 2017;18(12):1076-1081. PubMed CrossRef

6.Jennum P, Baandrup L, Ibsen R, et al. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: a population-based register study. Eur Neuropsychopharmacol. 2015;25(11):1906-1913. PubMed CrossRef

7.Lopez OL, Becker JT, Chang YF, et al. The long-term effects of conventional and atypical antipsychotics in patients with probable Alzheimer’s disease. Am J Psychiatry. 2013;170(9):1051-1058. PubMed CrossRef

8.Tible OP, Riese F, Savaskan E, et al. Best practice in the management of behavioural and psychological symptoms of dementia. Ther Adv Neurol Disorder. 2017;10(8):297-309. PubMed CrossRef

9.Fernando MS, Ince PG; MRC Cognitive Function and Ageing Neuropathology Study Group. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci. 2004;226(1-2):13-17. PubMed CrossRef

10.Garcia-Ptacek S, Farahmand B, Kåreholt I, et al. Mortality risk after dementia diagnosis by dementia type and underlying factors: a cohort of 15,209 patients based on the Swedish Dementia Registry. J Alzheimers Dis. 2014;41(2):467-477. PubMed CrossRef

11.Knopman DS, Rocca WA, Cha RH, et al. Survival study of vascular dementia in Rochester, Minnesota. Arch Neurol. 2003;60(1):85-90. PubMed CrossRef

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