作者：Susan Jeffrey
出處：WebMD醫學新聞
January 11, 2010 — 一篇新研究的結果確認輕微認知缺損(mild cognitive impairment，MCI)患者如果有糖尿病，則惡化成失智的風險增加。
研究者寫道，雖然之前的研究顯示糖尿病與MCI及失智都有關聯，但是還不清楚糖尿病是否會增加兩者間的轉變風險。
第一作者、英國倫敦國王學院精神科研究中心的Latha Velayudhan醫師等人結論表示，我們的研究顯示，輕微認知缺損且有糖尿病者，發生失智的風險增加，這表示需要改善糖尿病控制與相關及早介入之方法的研究。
他們的研究發現登載於1月號的英國精神醫學期刊(British Journal of Psychiatry)。
【早期發現】
研究者寫道，MCI病患發生失智的風險增加，不過，各研究指出的每年轉變率從1%到超過25%，預測失智惡化與轉變是有臨床重要性的，迄今，除了認知缺損之外，沒有可以明確地指出轉變風險增加的其他變項。
第2型糖尿病與加速有MCI之年長者的認知衰退有關，也增加失智的風險，包括阿茲海默氏症和血管型失智，不過，他們指出，雖然糖尿病和失智風險之間的關聯很「強烈」，還不清楚糖尿病是否會增加從MCI轉變為失智的風險。
在這篇文章中，Velayudhan醫師等人探究糖尿病和失智轉變的關聯，研究對象是根據Peterson氏規範、有MIC的103名患者。
在4年的追蹤期間，19人惡化成失智，多數可能是阿茲海默氏症，該診斷佔84%。校正社會人口統計學因素、出現脂蛋白E4風險對偶基因、病前智力與其他健康狀況之後，只有糖尿病與失智惡化有顯著關聯。
表. 與糖尿病有關的失智轉變風險
因素 | 風險比 | 95% CI |
糖尿病 | 2.9 | 1.1 – 1.73 |
CI = 信心區間
他們指出，這個研究世代多數是歐洲人，應對其他糖尿病盛行率較高的族群，或者其他種族進行研究。
研究作者們寫道，糖尿病增加失智風險的可能機轉，包括胰島素阻抗症候群、腦中的胰島素平衡問題、和/或高胰島素血症與其他。
他們結論表示，不論機轉為何，各年齡層、包括年長者的糖尿病盛行率預期增加，發生失智的風險也會增加。確認那些特別有惡化風險的人，將有助於早期的藥物與社會治療。
【研究發現不令人驚訝】
阿茲海默氏症協會醫療與科學主任Bill Thies博士受邀對這個新研究發現發表評論時表示，至少就流行病學看來，現在有相當確定的證據認為糖尿病和阿茲海默氏症之間有關聯。
不過，Thies博士指出，實際的機轉還不完全清楚，例如，第2型糖尿病增加了血管風險，會變成與阿茲海默氏症有關，或者是與其他葡萄糖代謝或腦中的胰島素效應因素更直接有關。雖然第2型糖尿病藥物rosiglitazone的試驗顯示對阿茲海默氏症病患無效，但有些小型研究認為，吸入型胰島素或許可以改善阿茲海默氏症的一些檢測表現。
Thies博士結論表示，目前這篇研究的內文看來，其結果並不令人驚訝，但是，證明你認為是真實的事情總是好事。
阿茲海默氏症研究信託與英國醫學研究委員會資助該研究，透過國家健康研究中心、生醫專門研究中心、位於南倫敦與墨滋里的國家健康服務基金信託、以及倫敦國王學院。作者們宣告沒有相關財務關係。
Diabetes Accelerates Conversion of Mild Cognitive Impairment to Dementia
By Susan Jeffrey
Medscape Medical News
January 11, 2010 — Results of a new study confirm that the presence of diabetes mellitus in people with mild cognitive impairment (MCI) is associated with an increased risk for progression to dementia.
Although previous studies have shown a link between diabetes and both MCI and dementia, it has not been clear whether diabetes increases the risk for conversion from one to the other, the researchers write.
"Our study demonstrates that individuals with mild cognitive impairment and diabetes are at increased risk of developing dementia," the researchers, with lead author Latha Velayudhan, DNB (Psychiatry), from the Institute of Psychiatry, King's College London, United Kingdom, conclude. "This suggests the need for studies of improved diabetes control and related approaches as possible strategies for early intervention."
Their findings are published in the January issue of the British Journal of Psychiatry.
Early Identification
People with MCI are at increased risk of developing dementia, although conversion rates range from 1% to more than 25% per year, depending on the study, the investigators write. "Prediction of progression to dementia — conversion — is of considerable clinical importance," they note. "To date, there is no variable other than cognitive impairment itself that unequivocally increases the risk of conversion."
Type 2 diabetes mellitus has been linked to accelerated cognitive decline in elderly people, development of MCI, and increased risk for dementia, including Alzheimer's disease and vascular dementia. However, although the association between diabetes and dementia risk is "robust," they note, it is not yet clear whether diabetes increases the risk for conversion from MCI to dementia.
In this article, Dr. Velayudhan and colleagues looked at the association between diabetes and dementia conversion in a population of 103 people with MCI by Peterson's criteria.
During 4 years of follow-up, 19 progressed to dementia, mostly probable or possible Alzheimer's disease, the diagnosis in 84%. After adjustment for sociodemographic factors, presence of the apolipoprotein E4 risk allele, premorbid IQ, and other health conditions, only diabetes mellitus was significantly associated with progression to dementia .
Table. Risk of Conversion to Dementia Associated With Diabetes Mellitus
| Factor | Hazard Ratio | 95% CI |
| Diabetes mellitus | 2.9 | 1.1 – 1.73 |
CI = confidence interval
This cohort was mostly white European participants, they note. Repeating this investigation in different populations where diabetes prevalence is higher, such as some ethnic groups, would be of interest.
Possible mechanisms by which diabetes might increase dementia risk include insulin resistance syndrome, disturbances in insulin homeostasis in the brain, and/or hyperinsulinemia, among others, the study authors write.
"Whatever the mechanism, with an expected increase in prevalence of diabetes in people of all ages, including older adults, the risk of developing dementia may increase," they conclude. "Identification of those at particular risk of progression might help to target early treatment — both pharmacological and social."
Findings Not Surprising
Asked for comment on these new findings, Bill Thies, PhD, chief medical and science officer for the Alzheimer's Association, pointed out that there is now a "pretty solid body of evidence" linking diabetes and Alzheimer's disease, at least at the epidemiologic level.
However, "exactly what the mechanism might be is not entirely clear," Dr. Thies added. Type 2 diabetes increases vascular risk, for example, which in turn has been linked to Alzheimer's disease, or the link may have something more directly to do with glucose metabolism or some other effect of insulin in the brain. Although trials of rosiglitazone, used to treat type 2 diabetes, had no effect in patients with Alzheimer's disease, some small studies have suggested that inhaled insulin may improve performance on some measures in Alzheimer's disease, he added.
In that context, then, the findings of the current study are not surprising, Dr. Thies concluded, but "it's always a good thing to document that the things you think are true really are."
The study was funded by the Alzheimer's Research Trust and the UK Medical Research Council and through the National Institute for Health Research, Specialist Biomedical Research Center for Mental Health at the South London & Maudsley National Health Service Foundation Trust, and King's College London. The authors have disclosed no relevant financial relationships.
Br J Psychiatry. 2010;196:36-40.
