The Impact of Pharmacological Treatments on Cognitive Function and Severity of Behavioral Symptoms in Geriatric Elder Patients with Dementia

不同藥物治療對於老年失智症病人之認知功能與精神行為症狀嚴重程度之影響

曾念生(Nian-Sheng Tzeng)；江瑋珊(Wei-Shan Chiang)；陳順益(Shun-Yi Chen)；周雨青(Yu-Ching Chou)；李昆明(Kun-Ming Lee)；黃三原(San-Yuan Huang)；葉啟斌(Chin-Bin Yeh)；陳俊延(Chun-Yen Chen)；張勳安(Hsin-An Chang)；高譽誠(Yu-Chen Kao)

cognitive function ； mini-mental status examination ； behavioral and psychological symptoms ； neuropsychiatric inventory ； 認知功能 ； 簡易智能狀態檢查 ； 精神行為症狀 ； 神經精神症狀問卷

台灣精神醫學

31卷1期（2017 / 03 / 01）

69 - 79+iii

英文

Objective: This study was to determine the impact of different pharmacological treatments on cognitive functions and the severity of the behavioral and psychological symptoms (BPSD) in elderly patients with dementia. Methods: The study was a prospective, and observational study. We examined 70 older patiens with dementia with the Mini-Mental Status examination (MMSE) and the Neuropsychiatric Inventory (NPI) Scale at each time of the outpatient visits at the 1st, 4th, and 12th week, to find out the impacts of antipsychotic drugs, mood stabilizers/ antidepressants, hypno-sedative, and cognitive enhancers/anti-dementia drugs. Results: The majority of dementia types were Alzheimer’s dementia (AD, n = 40, 57.1%) and vascular dementia (VaD, n = 28, 40%). The caregivers were their spouses (n = 10, 14.3%), or children (n = 53, 75.7%). We found that psychotropic medications, 27 (38.6%) of the patients used antipsychotic drugs, 25 (35.7%) mood stabilizers/antidepressants, 27 (38.6%) hypno-sedatives, and 48 (68.6%) cognitive enhancers/anti-dementia drugs. Those medications did not show any significant improvements of the MMSE at 12th weeks. Mood stabilizers/antidepressants reached a significant decrease in both the NPI severity and the caregiver distress scores. Conclusion: In this study, we found that patients with BPSD, receiving antipsychotics, mood stabilizers/antidepressants, hypno-sedative and cognitive enhancers/anti-dementia drugs did not improve the MMSE scores at the end of study, but that those receiving mood stabilizer/antidepressants showed a significant decrease on the behavioral disturbances measured by the NPI scale.

背景：這是一項精神科藥物，對失智症老人病人的門診研究。方法：在這前瞻性觀察性研究中，失智症老年人 (N = 70) 在第1、4、12 週接受簡易智能狀態檢查 (Mini Mental Status Examination [MMSE]) 和神經精神症狀問卷 (The Neuropsychiatric Inventory) 檢查，以了解的抗精神病藥、情緒穩定劑／抗憂鬱劑、催眠鎮靜及認知增強劑／抗失智藥物之影響。結果：病人依失智症類型依序為阿爾茲海默病性失智症 (n = 40，57.1%) 和血管性失智症 (n =28，40%)。主要的病人照顧者為配偶 (n = 10，14.3%)，或子女 (n = 53，75.7%)。有27 位(38.6%) 服用抗精神病藥，25 位 (35.7%) 情緒穩定劑／抗憂鬱藥，27 位 (38.6%) 催眠鎮靜劑，48 位 (68.6%) 認知增強劑／抗失智藥物。認知功能在第12 週，MMSE 均無顯著改善。情緒穩定劑／抗憂鬱藥對行為症狀嚴重性與照顧者困擾均有顯著下降。結論：此一觀察性研究中，使用前述各類藥物可能均不會改善在研究結束時的簡易智能狀態分數，使用情緒穩定劑／抗憂鬱藥可能神經精神症狀問卷分數下降。更大規模的觀察研究有其需要。

1. Chen, HM,Tsai, LJ,Chao, SY,Clark, MJ(2016).Report on the effects of individualized learning therapy on cognitive function and behavioral and psychological symptoms of dementia in the institutionalized older adults.J Nurs Res,24(4),300-310.
   連結：
2. Chiu, JH,Chen, CK,Chiang, SC,Chang, CJ,Sun, JJ(2007).A retrospective comparison study of risperidone and sulpiride for outpatients with dementia.Taiwanese Journal Psychiatry,21,90-99.
   連結：
3. Chiu, PY,Tsai, CT,Chen, PK,Liu, YL,Lai, TJ(2015).Frequency of early and late-onset dementias in a Taiwanese dementia clinic: first report on the Lin-Shin Dementia Registry Project.Taiwanese Journal of Psychiatry,29,29-39.
   連結：
4. Huang, SS,Liao, YC,Wang, WF,Lai, TJ(2012).The factors associated with burden of caring patients with dementia: a memory clinic based study.Taiwanese Journal Psychiatry,26,96-104.
   連結：
5. Hwang, JP(2006).Behavioral and psychological symptoms of dementia.Taiwanese Journal of Psychiatry,20,18-20.
   連結：
6. Adelman, RD,Tmanova, LL,Delgado, D,Dion, S,Lachs, MS(2014).Caregiver burden: a clinical review.JAMA,311,1052-1060.
7. Araki, T,Wake, R,Miyaoka, T(2014).The effects of combine treatment of memantine and donepezil on Alzheimer's disease patients and its relationship with cerebral blood flow in the prefrontal area.Int J Geriatr Psychiatry,29,881-889.
8. Bond, M,Rogers, G,Peters, J(2012).The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (Review of Technology Appraisal No. 111): a systematic review and economic model.Health Technol Assess,16,1-470.
9. Chen, YD,Zhang, J,Wang, Y,Yuan, JL,Hu, WL(2016).Efficacy of cholinesterase inhibitors in vascular dementia: an updated meta-analysis.Eur Neurol,75,132-141.
10. Chu, H,Yang, CY,Lin, Y(2014).The impact of group music therapy on depression and cognition in elderly persons with dementia: a randomized controlled study.Biol Res Nurs,16,209-217.
11. Clegg, A,Bryant, J,Nicholson, T(2001).Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review.Health Technol Assess,5,1-137.
12. Dick, JP,Guiloff, RJ,Stewart, A(1984).Mini-Mental State Examination in neurological patients.J Neurol Neurosurg Psychiatry,47,496-499.
13. Eagger, SA,Levy, R,Sahakian, BJ(1991).Tacrine in Alzheimer's disease.Lancet,337,989-992.
14. Folstein, MF,Folstein, SE,McHugh, PR(1975)."Mini- Mental State": a practical method for grading the cognitive state of patients for the clinician.J Psychiatr Res,12,189-198.
15. Fuh, JL,Liu, CK,Mega, MS,Wang, SJ,Cummings, JL(2001).Behavioral disorders and caregivers' reaction in Taiwanese patients with Alzheimer's disease.Int Psychogeriatr,13,121-128.
16. Gallassi, R,Di Sarro, R,Morreale, A,Amore, M(2006).Memory impairment in patients with late-onset major depression: the effect of antidepressant therapy.J Affect Disord,91,243-250.
17. Gauthier, S,Leuzy, A,Racine, E,Rosa-Neto, P(2013).Diagnosis and management of Alzheimer's disease: past, present and future ethical issues.Prog Neurobiol,110,102-113.
18. Gray, SL,Dublin, S,Yu, O(2016).Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study.Bri Med J,352,i90.
19. Hanley, JA,Negassa, A,Edwardes, MD,Forrester, JE(2003).Statistical analysis of correlated data using generalized estimating equations: an orientation.Am J Ерidemiol,157,364-375.
20. Heok, KE,Li, TS(1997).Stress of caregivers of dementia patients in the Singapore Chinese family.Int J Geriatr Psychiatry,12,466-469.
21. Hughes, TB,Black, BS,Albert, M(2014).Correlates of objective and subjective measures of caregiver burden among dementia caregivers: influence of unmet patient and caregiver dementia-related care needs.Int Psychogeriatr,1-9.
22. Hustey, FM,Meldon, SW,Smith, MD,Lex, CK(2003).The effect of mental status screening on the care of elderly emergency department patients.Ann Emerg Med,41,678-684.
23. Hwang, JP(2010).Second-generation antipsychotics for treatment of behavioral and psychological symptoms in dementia: indication or contraindication.Taiwanese Journal Psychiatry,24,81.
24. Kaufer, DI,Cummings, JL,Christine, D(1998).Assessing the impact of neuropsychiatric symptoms in Alzheimer's disease: the Neuropsychiatric Inventory Caregiver Distress Scale.J Am Geriatr Soc,46,210-215.
25. Lee, PE,Gill, SS,Freedman, M,Bronskill, SE,Hillmer, MP,Rochon, PA(2004).Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review.Bri Med J,329,75.
26. Lim, PP,Sahadevan, S,Choo, GK,Anthony, P(1999).Burden of caregiving in mild to moderate dementia: an Asian experience.Int Psychogeriatr,11,411-420.
27. Mioshi, E,Foxe, D,Leslie, F(2013).The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease.Alzheimer Dis Assoc Disord,27,68-73.
28. Mittal, V,Kurup, L,Williamson, D,Muralee, S,Tampi, RR(2011).Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence.Am J Alzheimers Dis Other Demen,26,10-28.
29. Mokhber, N,Abdollahian, E,Soltanifar, A(2014).Comparison of sertraline, venlafaxine and desipramine effects on depression, cognition and the daily living activities in Alzheimer patients.Pharmaco- psychiatry,47,131-140.
30. Nagata, T,Shinagawa, S,Nakajima, S(2015).Classification of neuropsychiatric symptoms requiring antipsychotic treatment in patients with Alzheimer's disease: analysis of the CATIE -AD study.J Alzheimers Dis,50,839-845.
31. Pan, YJ,Wu, CS,Gau, SS,Chan, HY,Banerjee, S(2014).Antipsychotic discontinuation in patients with dementia: a systematic review and meta-analysis of published randomized controlled studies.Dement Geriatr Cogn Disord,37,125-140.
32. Prick, AE,de Lange, J,Scherder, E,Twisk, J,Pot, AM(2016).The effects of a multicomponent dyadic intervention on the mood, behavior, and physical health of people with dementia: a randomized controlled trial.Clin Interv Aging,11,383-395.
33. Prince, M,Bryce, R,Albanese, E,Wimo, A,Ribeiro, W,Ferri, CP(2013).The global prevalence of dementia: a systematic review and metaanalysis.Alzheimers Demen,9,63-75.e2.
34. Puustinen, J,Nurminen, J,Kukola, M,Vahlberg, T,Laine, K,Kivela, SL(2007).Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly.Drugs Aging,24,1045-1059.
35. Rainer, MK,Masching, AJ,Ertl, MG,Kraxberger, E,Haushofer, M(2001).Effect of risperidone on behavioral and psychological symptoms and cognitive function in dementia.J Clin Psychiatry,62,894-900.
36. Shen, CW,Chen, YH(2012).Model selection for generalized estimating equations accommodating dropout missingness.Biometrics,68,1046-1054.
37. Sink, KM,Holden, KF,Yaffe, K(2005).Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.JAMA,293,596-608.
38. Taemeeyapradit, U,Udomittipong, D,Tepparak, N(2014).Characteristics of behavioral and psychological symptoms of dementia, severity and levels of distress on caregivers.J Med Assoc Thai,97,423-430.
39. Tan, LL,Wong, HB,Allen, H(2005).The impact of neuropsychiatric symptoms of dementia on distress in family and professional caregivers in Singapore.Int Psychogeriatr,17,253-263.
40. Tzeng, NS,Chang, CW,Hsu, JY,Chou, YC,Chang, HA,Kao, YC(2015).Caregiver burden for patients with dementia with or without hiring foreign health aides: a cross-sectional study in a northern Taiwan memory clinic.J Med Sci,35,239-247.
41. Vigen, CL,Mack, WJ,Keefe, RS(2011).Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD.Am J Psychiatry,168,831-839.
42. Wang, HF,Yu, JT,Tang, SW(2015).Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis.J Neurol Neurosurg Psychiatry,86,135-143.
43. Wang, J,Yu, JT,Wang, HF(2015).Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis.J Neurol Neurosurg Psychiatry,86,101-109.
44. Wang, M,Kong, L,Li, Z,Zhang, L(2016).Covariance estimators for generalized estimating equations (Gee) in longitudinal analysis with small samples.Stat Med,35,1706-1721.
45. Wolfson, C,Oremus, M,Shukla, V(2002).Donepezil and rivastigmine in the treatment of Alzheimer's disease: a best-evidence synthesis of the published data on their efficacy and cost-effectiveness.Clin Ther,24,862-886.
46. Zun, L,Howes, DS(1988).The Mental status evaluation: application in the emergency department.Am J Emerg Мed,6,165-172.

1. 簡戊鑑,鍾其祥,葉慧雯,葉啟斌,葉奕緯,黃三原,曾念生,張勳安,高譽誠,高廉程,周雨青,江瑋珊(2018).The Newly Diagnosed Amnestic Disorders and Dementia: A Nationwide, Cohort Study in Taiwan.臺灣精神醫學,32(1),18-28+i.