同時患有糖尿病與憂鬱症增加了失智風險


  【24drs.com】March 11, 2010 — 根據一篇新研究,同時患有糖尿病與重度憂鬱的病患,發生失智症的風險是只有糖尿病患者的三倍之多。
  
  第一作者、西雅圖華盛頓大學醫學院精神與行為科學系副主任、教授Wayne J. Katon醫師表示,這是個重要發現,因為隨著年紀增加,可能造成失智症「流行」率的新線索就愈發重要。
  
  Katon醫師向Medscape Psychiatry表示,我們正邁向老年人口增加的時代,每十年的失智症比率都上升,這造成Medicare保險體系的龐大支出,更別說病患與家屬所受的折磨有多大。
  
  Katon醫師表示,糖尿病和憂鬱症都是可以治療的,兩者也都是失智的風險因素,如果我們可以治療那些風險因素,我們或許可以減少疾病盛行率。
  
  Katon醫師表示,研究結果強調了糖尿病患進行憂鬱症篩檢、以及憂鬱症病患檢查糖尿病的重要性。
  
  該研究線上發表於1月28日的一般內科醫學期刊(Journal of General Internal Medicine)。
  
  名為「Pathways Epidemiologic Follow-Up Study」的前瞻世代研究,包括了來自華盛頓州Group Health 這個論人計酬制健康計畫的3,837名糖尿病患,開始時,研究對象完成病患健康問卷,蒐集精神疾病診斷與統計手冊第四版中的9個有關重度憂鬱症狀的資料。
  
  【失智編碼】
  研究5年後,使用國際疾病分類第九版臨床修正版(ICD-9-CM)編碼,針對門診和住院病患資料庫,確認存活且原本沒有失智之研究對象的失智發生率,包括了老年期失智症且無併發症者、阿茲海默氏症、血管型失智、其他未註明之失智症。
  
  在追蹤期間,超過15,468人年的資料中,199名病患(5.2%)符合至少一種ICD-9-CM的失智診斷初級定義,發生率為每1000人年有12.9例。
  
  開始時有重度憂鬱的455名病患中,在1671人年的追蹤期間,7.9%有新診斷的失智症,發生率為每1000人年有21.5例,而沒有重度憂鬱的3,382名病患中,在13,797人年的追蹤期間,有163名病患(4.8%)發生失智,發生率為每1000人年有11.8例。
  
  校正性別、年紀、種族、教育、罹糖尿病期間、糖尿病併發症、高血壓、健康習慣、其他變項之後,相較於沒有憂鬱者,重度憂鬱病患發生失智的風險比(HR)為2.69 (95%信心區間為 1.77 – 4.07)。
  
  排除研究前兩年內發生失智的病患之後,結果相似(校正模式的HR = 2.05 ),改用需有兩種或以上ICD-9-CM編碼的更保守失智定義之後,結果也是類似(校正HR = 2.77)。
  
  【雙向關係】
  Katon醫師表示,憂鬱和糖尿病是密切關聯的雙向關係,糖尿病患約有15%和20%會有明顯的臨床憂鬱症,有糖尿病者發生憂鬱的機會是沒有糖尿病者的 2- 3 倍。
  
  憂鬱增加發生糖尿病風險的可能原因是因為自我照護不佳,Katon醫師表示,憂鬱的糖尿病患不會遵守飲食規範、比較會肥胖、血糖更高,藥物順從性也更差。
  
  但是,不佳的自我照護未能用來解釋有憂鬱之糖尿病患失智風險增加的情況,目前的這個研究校正了開始時的體能活力、抽菸與其他健康習慣。
  
  【生物學解釋更有力】
  Katon醫師表示,這種看法是認為,憂鬱的生物因素,例如它對下視丘-腦垂腺軸的影響及較高的可體松值、它對自律神經系統的影響、以及對發炎前因子的影響,這些或許是可以用來解釋憂鬱和失智風險增加有關之更明顯且更有力的因素。
  
  研究者表示,憂鬱也可能是早期失智的前驅症狀,但是,排除研究前兩年時的失智診斷之後,憂鬱依舊與失智風險增加有關,因此,可能並非如此。
  
  糖尿病的併發症,如視力喪失或截肢,對於情緒會有重大影響,也會增加憂鬱風險。
  
  【篩檢的重要性】
  Katon醫師表示,一線照護醫師應篩檢糖尿病患有無憂鬱症,就像對這類病患篩檢抽菸情況一樣,而且,精神科醫師篩檢病患是否有糖尿病也一樣重要。
  
  他表示,精神病患者如精神分裂症和躁鬱症,糖尿病盛行率較高;慢性心智疾患者中,糖尿病比率高出2-3倍。
  
  Katon醫師表示,精神科醫師接受的訓練是診斷慢性心智疾病、監測病患的體重和血壓,開立一些可能引起肥胖的精神病藥物。
  
  研究限制之一是,並未藉由結構式精神病訪談診斷憂鬱症,只有在開始時檢測。其他研究限制包括,該研究採信自我報告的健康習慣且只有在開始時蒐集資訊,根據失智編碼辨識失智案例,因此與醫師對於該狀況的認知有關。
  
  阿茲海默氏症協會醫療與科學辦公室主任William Thies博士受邀對該研究發表評論時表示,這是個有趣的研究,但是並未釐清憂鬱和失智之間的可能關聯這個議題,他指出,有些研究發現類似的關聯,但是有些則沒有。
  
  Thies博士表示,我認為這是個有趣的研究,但是,它對於憂鬱和失智之間的關聯並無立即而明確的討論,未能引起我的任何共鳴。
  
  他表示,另一方面,該研究指出的糖尿病與失智的關聯則已經相當確立。
  
  Thies博士指出,雖然研究一開始包括了3,837名病患,其中,在開始時有重度憂鬱者只有36人在追蹤期間有新的失智診斷。
  
  Thies博士表示,最後,他們有關憂鬱及糖尿病和失智的資料只與那36人有關,因此,如果你增加足夠的警告,符合的人數會越來越少,我的粗略概算是,(如果只有)10個病患的差異將會讓比率約略相當。
  
  Katon醫師指出他接受Wyeth、Eli Lilly、Forest與Pfizer等藥廠的演講獎金,也擔任Eli Lilly和Wyeth的諮詢委員,其他研究作者的宣告登載於原始文獻中。
  
  J Gen Intern Med. 線上發表於2010年2月28日。

Comorbid Diabetes and Depression Increase Dementia Risk

By Pauline Anderson
Medscape Medical News

March 11, 2010 — Patients with diabetes who also have major depression have almost a 3-fold increased risk of developing dementia compared with patients with diabetes alone, according to a new study.

This finding is important because as the population ages, it is becoming increasingly important to uncover clues about what is contributing to the "epidemic" rates of dementia, said lead study author Wayne J. Katon, MD, professor and vice chair, Department of Psychiatry & Behavioral Sciences, University of Washington School of Medicine, Seattle.

"We’re moving into an era where we have a much larger aging population than ever before and the rates for dementia increase with each decade. That’s certainly going to cost the Medicare system a huge amount of money, not to mention the suffering to families," Dr. Katon told Medscape Psychiatry.

Both diabetes and depression are treatable conditions, and both are risk factors for dementia, said Dr. Katon. "If we’re able to treat those risk factors, we may be able to decrease the prevalence of this illness," he said.

The results of the study underline the importance of screening for depression among patients with diabetes and for diabetes in patients with depression, said Dr. Katon.

The study was published online January 28 in the Journal of General Internal Medicine.

The prospective cohort Pathways Epidemiologic Follow-Up Study included 3837 patients with diabetes enrolled in Group Health, a mixed-model capitated health plan in the state of Washington. At baseline, the subjects completed the Patient Health Questionnaire, which gathers information on the 9 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) major depressive symptoms.

Dementia Codes

After about 5 years, the presence of dementia in surviving subjects who had no dementia at baseline was determined from both outpatient and inpatient databases using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, which include senile dementia uncomplicated, Alzheimer’s disease, vascular dementia, and dementia not otherwise specified.

During the follow-up period, 199 participants (5.2%), representing more than 15,468 person-years of follow-up, met the primary definition of dementia with at least 1 ICD-9-CM dementia diagnosis for an incidence rate of 12.9 per 1000 person-years.

Of the 455 patients with major depression at baseline, 7.9% had a new diagnosis of dementia during follow-up during 1671 person-years, for an incidence rate of 21.5 per 1000 person-years. This compared with 163 of 3382 patients (4.8%) without major depression during 13,797 person-years, for an incidence rate of 11.8 per 1000 person-years.

After adjusting for sex, age, race, education, diabetes duration, diabetes complications, hypertension, health habits, and other variables, the hazard ratio (HR) for developing dementia for patients with major depression compared with those without depression was 2.69 (95% confidence interval, 1.77 – 4.07).

Excluding patients who developed dementia during the first 2 years of the study had similar results (HR = 2.05 in an adjusted model), as did using the more conservative definition of dementia that requires 2 or more ICD-9-CM codes (adjusted HR = 2.77).

Bidirectional Relationship

Depression and diabetes are closely linked in a "bidirectional" relationship, said Dr. Katon. Between 15% and 20% of people with diabetes will have a significant clinical depression, and depression is 2 to 3 times more common among people with diabetes compared with those without diabetes, he said.

One way depression may raise the risk for developing diabetes is that it leads to poor self-care. "Depressed diabetics don’t follow their diet, they smoke more, they’re more obese, have higher blood sugars, and are more apt to be nonadherent to their medications," said Dr. Katon.

But poor self-care does not appear to explain the increased risk for dementia among diabetic patients who have depression. The current study adjusted for baseline physical activity, smoking, and other health habits.

Biological Explanation More Potent

"This suggests that maybe the biological parts of depression, such as its effect on the hypothalamic pituitary axis and higher cortisol levels, its effect on the autonomic nervous system, and the effect on proinflammatory factors, may be more salient, more potent, reasons for why depression is associated with increased risk for dementia," said Dr. Katon.

It is also possible that depression could be a prodromal symptom of early-stage dementia. But the finding that depression remained associated with an increased risk for dementia after excluding a diagnosis of dementia in the first 2 years of the study suggests that this is likely not the case, the study authors write.

Diabetes may also increase depression risk through complications such as loss of eyesight or amputation, which can have a profound impact on mood.

Importance of Screening

Primary care physicians should screen patients with diabetes for depression just as they would screen such patients for smoking, said Dr. Katon. But it is also important for psychiatrists to screen their patients for diabetes.

"People with psychiatric illnesses like schizophrenia and bipolar disorder have a much higher prevalence of diabetes; among the chronically mentally ill, the rates of diabetes are 2- to 3-fold higher," he said.

Psychiatry residents are being trained to diagnose chronic medical illnesses and to monitor patients’ weight and blood pressure, said Dr. Katon, adding that some psychiatric medications can cause obesity.

A limitation of the study was that a diagnosis of depression was not made through a structured psychiatric interview and was only measured at baseline. Other limitations include the study's reliance on self-reports of health habits only at baseline and that identification of dementia was based on dementia codes and therefore relied on physician recognition of the condition.

Approached for a comment on the study, William Thies, PhD, chief medical and scientific officer, Alzheimer’s Association, said it was interesting but does not sort out the "confusion" surrounding the issue of a possible link between depression and dementia. He noted that some studies have found such a link, whereas others have not.

"I think this study is interesting but it would not immediately solidify the discussion of the relationship of depression and dementia," said Dr. Thies. "It doesn’t ring any huge bells for me.”

On the other hand, the research linking diabetes to dementia is "fairly well established," he said.

Dr. Thies noted that although the study initially included 3837 patients, only 36 of those with major depression at baseline had a new diagnosis of dementia during follow-up.

"Ultimately, their data about depression and diabetes and dementia sit on the shoulders of 36 people," said Dr. Thies. "So if you add enough caveats, the numbers get smaller and smaller. My rough calculation is that a difference of 10 patients is going to make the rates about equal."

Dr. Katon reports that he has received honoraria for lectures from Wyeth, Eli Lilly, Forest, and Pfizer pharmaceutical companies and serves on the Advisory Board for Eli Lilly and Wyeth. Disclosures of the study coauthors are available in the original study.

J Gen Intern Med. Published online January 28, 2010.

    
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