憂鬱症可能是失智症前驅症狀


  【24drs.com】新研究顯示,憂鬱症逐漸增加,相對於更穩定的症狀,與發生失智症的風險增加有關。
  
  荷蘭鹿特丹Erasmus醫學中心研究者進行的一篇縱向研究顯示,失智風險因不同的憂鬱症病程而異,憂鬱症狀隨著時間增加者,更可能發生失智,研究者指出,這個發現認為,憂鬱症可能是失智症的前驅症狀。
  
  M. Arfan Ikram博士領銜的作者們寫道,透過在11年間反覆測量憂鬱症狀,就我們所知,我們是第一篇評估憂鬱症病程和失智症風險之關聯的研究。
  
  這些結果發表於7月的Lancet Psychiatry期刊。
  
  根據研究者表示,老年時的憂鬱症狀和偶發之失智的關聯已被廣泛研究,但是,通常是在單一時間點評估此一關聯。
  
  他們寫道,這種做法忽視了憂鬱症的病程,鑑於其緩解性和復發性,可能可以提供進一步地深入瞭解憂鬱症與老年失智症的複雜關聯。因此,我們在約十年期間反覆測量這群成年人的憂鬱症狀,以研究失智症的後續風險。
  
  為了研究,Ikram博士等人評估了鹿特丹研究的資料,包括了1993-2004這11年間、荷蘭55歲以上樣本人口的憂鬱症症狀資訊。該研究包括了3,325名參與者,年齡中位數74歲、60%是女性、434 人發生偶發性失智。
  
  根據憂鬱症狀的五種軌跡之一、以及荷蘭版的流行病學憂鬱症中心量表(Center for Epidemiology Depression Scale[CES-D])分數將患者分類,患者被分類為:穩定型、低分數;分數中高但之後降低;開始時分數低、之後增加、之後降低;開始時分數低、之後逐漸增加;開始時分數高且持續偏高。
  
  相較於低憂鬱症狀軌跡的患者,憂鬱症狀增加的患者發生失智症的關聯性最強(風險比[HR]1.42; P = .024)。反之,單一時間點有高度憂鬱症狀但之後緩解的患者,與失智症風險並無關聯。
  
  校正偶發中風(HR, 1.58; P = .004)、限制阿茲海默氏症作為一項結果(HR, 1.44; P = .034)、納入死亡率作為競爭風險(HR, 1.45; P = .019)之後,憂鬱症狀增加依舊有比較強的關聯。
  
  作者們指出,藉由反覆測量憂鬱症狀,我們注意到,臨床診斷失智症的前幾年,即出現憂鬱症狀且逐漸增加,這或許是失智症前驅症狀的一部份。
  
  校正抗憂鬱劑使用發現, 憂鬱症狀軌跡高、增加與降低組中,與失智症風險降低約10%有關。
  
  雖然使用抗憂鬱劑之關聯的機轉還未被充分瞭解,作者們指出,理論包括:長期使用抗憂鬱藥導致認知儲備能力受損以及降低膽鹼活性,在動物模式中顯示,會增加beta-amyloid之濃度。
  
  作者們寫道,整體結果與「年長者的憂鬱症狀可能是失智症的前驅症狀或早期失智症」之假設一致。
  
  澳洲雪梨新南威爾斯大學健康腦部老化中心發育障礙系Simone Reppermund博士對此篇研究的評論中表示,目前,有關憂鬱症和失智症之機轉的最強證據,在2013年英國精神病學期刊發表的一篇大型系統性回顧中提出,指向血管風險因素。
  
  Reppermund博士寫道,血管疾病和老年憂鬱症的雙向關係有證據存在;有些研究的結果支持憂鬱症和後續血管疾病之關聯,其他則是提出血管疾病促進發生憂鬱症的證據。
  
  Reppermund博士指出,在這些研究中,憂鬱症和失智症都與社會互動和其他生活形態因素有關,他也指出,遲發性和早發性憂鬱症之間的區別也很重要。
  
  Reppermund博士指出,新研究結果讓我們更進一步接近憂鬱症是否是失智症風險因素的答案,反之亦然。
  
  資料來源:http://www.24drs.com/
  
  Native link:Depression May Be a Dementia Prodrome

Depression May Be a Dementia Prodrome

By Nancy A. Melville
Medscape Medical News

A gradual increase in depressive symptoms, as opposed to more stable symptoms, is linked to an increased risk of developing dementia, new research shows.

A longitudinal study conducted by investigators at Erasmus Medical Center in Rotterdam, the Netherlands, showed that dementia risk differed with different courses of depression, such that individuals with depressive symptoms that increased over time were more likely to develop dementia. This finding, the investigators note, suggests that depression may be a prodrome of dementia.

"By leveraging repeated measures of depressive symptoms over an 11-year period, our study is the first to our knowledge to assess the course of depression in relation to risk of dementia," the authors, led by M. Arfan Ikram, MD, PhD, write.

The findings were published in the July issue of Lancet Psychiatry.

According to investigators, the link between late-life depressive symptoms and incident dementia has been studied extensively, but the relationship has typically been assessed at a single time point.

"Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into the complex association of depression with dementia. We therefore repeatedly measured depressive symptoms in a population of adults over a decade to study the subsequent risk of dementia," they write.

For the study, Dr Ikram and colleagues evaluated data from the the Rotterdam Study, which included information on depressive symptoms in a sample of individuals aged 55 years and older in the Dutch population over an 11-year period, from 1993 to 2004.

The study included 3325 participants. The median age of the participants was 74 years; 60% were women; and 434 participants developed incident dementia.

Patients were categorized according to one of five trajectories of depressive symptoms, as determined on the basis of scores on the Dutch version of the Center for Epidemiology Depression Scale (CES-D). Patients were categorized as having stable, low scores; scores that were moderately high but then decreased; scores that were initially low, then increased, then decreased; scores that were initially low but then steadily increased; and scores that were initially high and that remained so.

The strongest association with the development of dementia was seen among patients with increasing depressive symptoms, in comparision with patients with the low depressive symptom trajectory (hazard ratio [HR] 1.42; P = .024).

Conversely, no association with dementia risk was seen in patients who had a high degree of depressive symptoms at a single time point, followed by remission.

The stronger association seen with increasing depressive symptoms remained after adjusting for factors that included incident stroke (HR, 1.58; P = .004), placing a restriction on Alzheimer's disease as an outcome (HR, 1.44; P = .034), and accounting for mortality as a competing risk (HR, 1.45; P = .019).

"By repeatedly measuring depressive symptoms we noted the appearance and steady increase of depressive symptoms several years before the clinical diagnosis of dementia, probably as part of the dementia prodome," the authors note.

Adjustment for the use of antidepressants was associated with a reduction in the risk for dementia by approximately 10% in groups with high, increasing, and decreasing trajectories of depressive symptoms.

Although the mechanisms of the relation with antidepressant use are not well understood, the authors note that theories include "impairment of the cognitive-reserve capacity and reduced cholinergic activity due to the long-term use of antidepressants, which has been shown to increase beta-amyloid concentrations in animal models."

The overall findings are consistent with the hypothesis that depressive symptoms in older persons may represent a prodrome or an early stage of dementia, the authors write.

Currently, the strongest evidence of mechanisms linking depression and dementia, described in a large, systematic review published in the British Journal of Psychiatry in 2013, points to vascular risk factors, notes Simone Reppermund, PhD, of the Department of Developmental Disability and the Centre for Healthy Brain Ageing, at the University of New South Wales, in Sydney, Australia, in a commentary published with the study.

"Evidence exists for a bidirectional relationship between vascular disease and late-life depression; findings from some studies support an association between depression and subsequent vascular disease, and others provide evidence that vascular disease promotes the development of depression," Dr Reppermund writes.

In studies, depression and dementia have been linked with regard to social interaction and other lifestyle factors, Dr Reppermund notes. He also indicates the importance of differentiating between late-onset and early-onset depression.

The new findings "have brought us one step closer to answering whether depression is a risk factor for dementia or vice versa," Dr Reppermund adds.

The study received funding from the Erasmus Medical Center; ZonMw; the Netherlands Ministry of Education Culture and Science; and the Netherlands Ministry for Health, Welfare and Sports. The authors and Dr Reppermund have disclosed no relevant financial relationships.

Lancet Psychiatry. 2016;7:593-595, 628-635.

    
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