忧郁症可能是失智症前驱症状


  【24drs.com】新研究显示,忧郁症逐渐增加,相对于更稳定的症状,与发生失智症的风险增加有关。
  
  荷兰鹿特丹Erasmus医学中心研究者进行的一篇纵向研究显示,失智风险因不同的忧郁症病程而异,忧郁症状随著时间增加者,更可能发生失智,研究者指出,这个发现认为,忧郁症可能是失智症的前驱症状。
  
  M. Arfan Ikram博士领衔的作者们写道,透过在11年间反覆测量忧郁症状,就我们所知,我们是第一篇评估忧郁症病程和失智症风险之关联的研究。
  
  这些结果发表于7月的Lancet Psychiatry期刊。
  
  根据研究者表示,老年时的忧郁症状和偶发之失智的关联已被广泛研究,但是,通常是在单一时间点评估此一关联。
  
  他们写道,这种做法忽视了忧郁症的病程,监于其缓解性和复发性,可能可以提供进一步地深入了解忧郁症与老年失智症的复杂关联。因此,我们在约十年期间反覆测量这群成年人的忧郁症状,以研究失智症的后续风险。
  
  为了研究,Ikram博士等人评估了鹿特丹研究的资料,包括了1993-2004这11年间、荷兰55岁以上样本人口的忧郁症症状信息。该研究包括了3,325名参与者,年龄中位数74岁、60%是女性、434 人发生偶发性失智。
  
  根据忧郁症状的五种轨迹之一、以及荷兰版的流行病学忧郁症中心量表(Center for Epidemiology Depression Scale[CES-D])分数将患者分类,患者被分类为:稳定型、低分数;分数中高但之后降低;开始时分数低、之后增加、之后降低;开始时分数低、之后逐渐增加;开始时分数高且持续偏高。
  
  相较于低忧郁症状轨迹的患者,忧郁症状增加的患者发生失智症的关联性最强(风险比[HR]1.42; P = .024)。反之,单一时间点有高度忧郁症状但之后缓解的患者,与失智症风险并无关联。
  
  校正偶发中风(HR, 1.58; P = .004)、限制阿兹海默氏症作为一项结果(HR, 1.44; P = .034)、纳入死亡率作为竞争风险(HR, 1.45; P = .019)之后,忧郁症状增加依旧有比较强的关联。
  
  作者们指出,藉由反覆测量忧郁症状,我们注意到,临床诊断失智症的前几年,即出现忧郁症状且逐渐增加,这或许是失智症前驱症状的一部份。
  
  校正抗忧郁剂使用发现, 忧郁症状轨迹高、增加与降低组中,与失智症风险降低约10%有关。
  
  虽然使用抗忧郁剂之关联的机转还未被充分了解,作者们指出,理论包括:长期使用抗忧郁药导致认知储备能力受损以及降低胆碱活性,在动物模式中显示,会增加beta-amyloid之浓度。
  
  作者们写道,整体结果与「年长者的忧郁症状可能是失智症的前驱症状或早期失智症」之假设一致。
  
  澳洲悉尼新南威尔斯大学健康脑部老化中心发育障碍系Simone Reppermund博士对此篇研究的评论中表示,目前,有关忧郁症和失智症之机转的最强证据,在2013年英国精神病学期刊发表的一篇大型系统性回顾中提出,指向血管风险因素。
  
  Reppermund博士写道,血管疾病和老年忧郁症的双向关系有证据存在;有些研究的结果支持忧郁症和后续血管疾病之关联,其它则是提出血管疾病促进发生忧郁症的证据。
  
  Reppermund博士指出,在这些研究中,忧郁症和失智症都与社会互动和其它生活形态因素有关,他也指出,迟发性和早发性忧郁症之间的区别也很重要。
  
  Reppermund博士指出,新研究结果让我们更进一步接近忧郁症是否是失智症风险因素的答案,反之亦然。
  
  资料来源: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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