摘要
背景：目前有關失智症存活研究，大多是針對全部失智症或單一退化性阿茲海默氏症。由於失智症的成因是異質性，有退化性也有血管性及其他特殊狀況，分析時針對全部失智症可能會低估某些血管性因子對失智症亞型的影響。針對血管性失智症病人的存活分析及死因探討文獻很少。本研究為一個世代研究的資料結構，完整記錄病人從中風後到血管性失智症，及後來的併發症及最後死亡的一連串過程，並以此為基礎，探討影響血管性失智症存活的可能危險因子有哪些？ 目標：本研究為一個血管性失智症存活的前驅性研究，主要探討危險因子，包括心血管因子(例:糖尿病、高血壓、心絞痛、心房顫動等)、社會經濟人口學因子(例:年紀、性別等)，及中風後的併發症(例:臥床、中風後癲癇等)、住院狀態(例:肺炎、心衰竭、敗血性休克等)、中風後到血管性失智症發病的時間長短、中風後腦部影像學表現等，對血管性失智症存活是否有影響 ? 其中包括中風後腦部影像學的表現，不同分類是否造成病人存活曲線的差異？及累積多重危險因子是否增加病人死亡機率？及血管性失智症併發症相關死因分析，進而能協助臨床醫師，針對高風險性血管性失智症病人，提早做藥物介入、及衛教預防，以降低死亡機率。 方法：本試驗為一回溯性世代追蹤研究。採病歷回顧的方法，從2004 年開始至2009年, 收集了耕莘醫院的失智症病人共500人，從其中選取血管性失智症的病人共54人。參與者年紀在65歲至99歲。收案時間為5年。所有的失智症病人經神經內科醫師依一九九三年由NINDS-AIREN (National Institute of Neurological Disorders and Stroke-Association International pour la Recherché et l'Enseignement en Neurosciences)所公佈的血管性失智症診斷標準診斷為血管性失智症。追蹤期間有一個標準流程：測血壓、體重、身高及抽血檢查膽固醇、血糖、甲狀腺功能、為他命B12、葉酸、菸酸、血鈣濃度、梅毒、愛滋病篩檢等。此外，利用臨床失智量表、及中文版簡短式智能評估來評估病人認知功能下降程度。另外也用腦部影像學，包括腦部斷層掃描、腦部核磁共振影像來評估病人中風後的嚴重度，及發生失智症時腦部萎縮程度。統計方法，一開始先以Fisher的精確檢定方法(Fisher's exact test)進行危險因子和VaD死亡，進行關聯性檢定。再以皮爾森相關係數(Pearson correlation coefficient)測試危險因子之間及其和VaD死亡關聯性。最後用邏輯氏回歸(Logistic regression)，分析危險因子和腦中風後腦部受損區域的關係。存活分析用Kaplan-Meier方法算半存活期，及5年存活率，用Log-Rank test檢定存活函數間差異，並用Cox 回歸模型去評估危險因子的死亡相對風險。 結果：我們的病人平均年紀是81.53±7.36歲。研究結束時共有12人死亡。 血管性失智症病人半存活期 4.96年。死亡原因如下：8人死於吸入性肺炎、1人死於外傷性蜘蛛網膜下出血、1人死於重覆性腦中風(缺血型)、1人死於急性心肌梗塞、1人死於肺癌。使用Kaplan-Meier Method 做出存活曲線，發現無心衰竭的VaD患者，比有心衰竭的VaD患者較好的存活情形，在開始的時間點差異很小，然後隨著時間越長相差越大。以Cox回歸模型去分析VaD病人的年齡、性別、危險因子、及中風後的併發症結果如下：心衰竭的RR為6.71,(95%CI= (1.71,26.25))，達統計上顯著的差異(p=0.0062)。敗血性休克的RR為4.98 (95%CI= (1.405,17.67))，達統計上顯著的差異(p=0.0129)。因為心衰竭和敗血性休克發生的時間可能和死亡有關，將心衰竭、和敗血敗血性休克，此二個變數視為時間相依的變數，以多變項的Cox回歸模型去分析，結果如下：心衰竭的迴歸係數為HR為2.14 (p=0.479 )。敗血性休克HR為33.20 (p <0.0001)。在調整心衰竭有無後，敗血性休克對VaD相關死亡達統計上意義。有高膽固醇的VaD病人，相較於無高膽固醇的VaD病人，RR為2.53，有較差的存活情形的趨勢，但未達統計上顯著的差異(p =0.1825)。在多重血管因子分析方面，有三種心血管因子的患者相較於二種心血管因子的患者較差的存活情形的趨勢，但用Log-Rank test檢定，則未達統計上顯著的差異(p=0.4280)。腦部影像學方面，以NINDS-AIRE影像診斷分類來做分層，發現中風後腦部影像為大腦室旁白質化患者，有最好的存活情形，有單次腦部關鍵性梗塞的腦中風的患有最差的存活情形的趨勢，但用Log-Rank test檢定不同存活函數間差異，則未達統計上顯著的差異(p=0.5988)。 結論：血管性失智症病人的5年存活率為34%。吸入性肺炎是血管性失智症病人主要死因。敗血性休克、心衰竭為影響VaD存活的時間相依變數，造成敗血性休克主因為吸入性肺炎，在調整心衰竭有無後，有敗血性休克相較於無敗血性休克的病人增加33.20倍死亡風險。累積多重血管性因子的VaD病人，有較有較差的存活率的趨勢。影像學方面，以NINDS-AIRE影像診斷分類來做分層，中風後腦部影像為大腦室旁白質化患者，有最好的存活情形的趨勢，有單次腦部關鍵性梗塞的腦中風的患有最差的存活情形的趨勢。
並列摘要
Background There were many survival suturies of Alzheimer's Disease or oveall dementia. But,the study about survival of vascular dementia was few.It is fact that the etiologies of dementia are variable.The effect of vascular risk factors on dementia mortality were underestimated due to the error anaylsis of oveall dementia patients rather than vascular dementia patients.Our study was a longitudinal study of patients of vascular dementia.We recorded the whole history from stroke to vascular dementia and final mortality course in hospital.Based on the records , we want to know what risks factors were related to mortality of vascular dementia. Objective To investigate what risks factors were contributioned to mortality of vascular dementia.The risk factors include as follows: age、gender、diabetes mellitus、hypertension、angima、atrial fibrillation、poststrpke bed-ridden state、poststroke epilepsy、congestive heart failure、sepsis、the time between stroke and dementia、poststroke brain image findings.According to the survival study of vascular dementia, we could know what risk factors were highly related to mortality and we can early prevent it with drugs or health education. Method We used medical record review system to identify cases of vascular dementia from January 1, 2004 to December 31, 2009. 54 patients were identified by the criteria of National Institute of Neurological Disorders and Stroke -Association International pour la Recherché et l'Enseignement en Neurosciences (NINDS –AIREN criteria) Patients with VaD were followed from the day of VaD diagnosis to death, or the end of study. All the patients were arranged a series of tests as follows, neurological examination revealed focal neurological symptoms and signs, and serological test for dementia survey, such as T4, TSH, and VDRL. Besides, Brain CT or MRI was done to check the poststroke states and brain atrophy. Cox proportional hazards models were used to evaluate the effects of risk factors on VaD. In addition, the estimated median survival time and five-year survival rate were obtained from the Kaplan-Meier method. Result The mean age of VaD was 81.53±7.36 years.Five year survival rate was 34%. At the ending of study, there were 12 deaths among patients. There were 8 patients died from aspiration pneumonia, 1 patients died from recurrent stroke, and 1 patient died from lung cancer,1 patient died from traumatic SAH due to fall down. The RR of death was 32.27(95%CI, 6.04-172.4) in VaD patients with congestive heart failure. The RR of death was 44.79(95%CI,12.10-165.8) in VaD patients with septic shock.The Kaplan-Meier survival curves showed the trend in poor survival amongVaD patients with multiple vascular factors.Besides,VaD patients with brain image showed periventricular white matter change has better survival tham patients with brin image showed a single strategically infarct. Conclusion Five-year survival rate was 34%. Aspiration Pneumonia was the major mortality cause in our patients. Septic shock and CHF were time-dependent variables in survival of VaD. The major cause of Sepsis was aspiration pneumonia.The RR of death was 33.20 in VaD patients with septic shock adjusted by CHF.There was trend with lower survival rate among VaD patients of multiple vascular risk factors.
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延伸閱讀
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