憂鬱早發於失智：有共同的病因、病因或是前驅症狀

Depression Precedes Dementia: Shared Common Etiologies, Cause, or Prodrome

憂鬱症與失智症常常併存，了解兩者的關係有助於臨床治療與預防。當憂鬱診斷發生在 失智之前，憂鬱與失智可能有共同的病因，憂鬱可能是失智的病因之一，或是憂鬱只是失智 的前驅症狀之一。兩者共同的病因包括腦部的缺血性病變、營養狀態、與 Apolipoprotein E gene (ApoE)。腦部缺血性變化同時是憂鬱與認知功能減退的危險因子；不飽和脂肪酸與同 胱胺酸可能也是共同病因；ApoE ε4 是阿滋海默氏症的危險對偶基因，但與憂鬱的相關的研 究結果仍不一致。憂鬱會活化腎上腺皮質促性腺激素分泌，過度的分泌對大腦有神經毒性， 尤其是海馬迴。後設研究發現憂鬱症與失智症兩者診斷時間差與發展失智的危險正相關，支 持憂鬱是失智的病因之一的說法。但即使如此，憂鬱症經過抗憂鬱劑的治療後，病人的認知 功能也並不能回復。或是，當憂鬱症狀發生時，其實腦部的失智退化性病變已經在進行了， 只是臨床上認知障礙表徵未達失智症的診斷，此時憂鬱可能是失智症的前驅症狀。有研究發 現，晚發的憂鬱病史有愈高失智的危險。共同的病因，憂鬱症是失智症的病因或是憂鬱症是 失智症的前驅症狀，三種的關係都有文獻支持，顯示憂鬱症有高異質性。仍需針對這些相關 聯進行更多的治療研究，期待可降低憂鬱發展成失智的風險。

Depression and dementia coexist often. To elucidate their relationship that the onset of depression precedes dementia is clinically worthwhile. Both conditions may share common etiologies. Depression may etiologically contribute to the de-velopment of dementia, or it may be just a prodrome of dementia. Evidences have suggested the possible shared common etiologies of depression and dementia are ischemic brain lesions, abnormal states in nutrition, and the existence of apolipo-protein E gene (ApoE). Ischemic brain disease may play a surrogate rôle to de-velop both depression and cognitive impairment. Nutrition status, such as polyun-saturated fatty acids or homocysteine, is the major interest of this issue. Subjects carrying the ApoE ε4 allele of the have a higher risk of developing Alzheimer’s disease (AD), but its association with depression is inconsistent. Depression can activate adrenal cortical gonadotropin secretion, which thus can have neurotoxic effect on the hippocampus. One meta-analysis study has been found that there was an association exists between interval between diagnoses of depression and AD and an increased risk of developing AD, supporting that depression may cause AD. However, clinical studies do not optimistically suggest cognitive prognosis of late life depression after a course of antidepressant treatment. The last possibility is that a neurodegenerative process underpins when depression emerges before the threshold of diagnosis of dementia can be made. Cognitive dysfunction in late-life depression may be explained by the depression itself representing a prodromal phase of dementia. That a recent history of depression is associated with increased risk of Alzheimer’s disease, can support the speculation. Current evidence sup-ports all possibilities that depression can be one of the causes, a prodromal sign of dementia, or share common etiologies with dementia. Further treatment focusing on the relationships is needed to prevent the elderly patients with depression from converting to dementia later on.