痴呆症风险与维生素D

大家好，欢迎收听精神药理学研究所播客。我是主持人Richard Suber医生，在这里我们将分享临床经验，助您掌握领域最新动态。设想您正接诊68岁的Johnson女士，她因记忆逐渐衰退而忧心忡忡。

Hi, and welcome to the Psychopharmacology Institute podcast. I'm your host, Doctor. Richard Suber, this is the place where we share clinical pearls to keep you updated in the field. Imagine you're sitting from Mrs. Johnson, a 68 year old patient concerned about her gradually declining memory.

她的母亲72岁时确诊阿尔茨海默病，她非常害怕重蹈覆辙。'我能做些什么来预防吗？朋友们推荐的维生素有用吗？'她问道。作为临床医生，我们常遇到这类关于神经退行性疾病预防措施的疑问。

Her mother was diagnosed with Alzheimer's at 72 and she's terrified of following the same path. Is there anything I can do to prevent this? She asks. What about the vitamins my friends keep recommending? Well, as clinicians, we often face these questions about preventative measures against neurodegenerative diseases.

相关证据体系正在持续更新。今天我们将探讨一项引人入胜的新研究——看似简单的充足维生素D水平可能在预防痴呆症中发挥重要作用。您可能听说过地中海饮食、规律锻炼和认知刺激作为认知衰退的潜在保护因素，但补充剂呢？最近一项小型研究表明，包含ω-3脂肪酸、维生素B12、辅酶Q10、维生素C、益生菌甚至猴头菇提取物等补充剂的生活方式干预能延缓阿尔茨海默病进展。

And the evidence landscape is regularly evolving. Today, we'll explore fascinating new research suggesting that something as simple as adequate vitamin D levels might play a significant role in preventing dementia. You've likely heard about the Mediterranean diet, regular exercise, and cognitive stimulation as potential protective factors against cognitive decline. But what about supplements? In a recent small study showing that lifestyle interventions slowed Alzheimer's progression, researchers included various supplements such as omega-three fatty acids, vitamin B12, coenzyme Q, vitamin C, probiotics, and even lion's mane mushroom extract.

这些物质均显示出延缓认知衰退的潜力或理论机制。现在，一项基于英国生物银行数据的大规模前瞻性队列研究提供了有力证据：维生素D可能影响包括阿尔茨海默病和血管性痴呆在内的主要神经认知障碍的发展。鉴于维生素D缺乏的普遍性（约25%美国人和40%欧洲人受影响），该发现尤为值得关注。本期节目我们将探讨Scott Beach医生对该重要研究及其临床意义的分析。

Each of these has shown promise or has theoretical mechanisms for slowing cognitive decline. Now, a substantial new prospective cohort study using data from the UK Biobank adds compelling evidence that vitamin D may impact the development of major neurocognitive disorders, including Alzheimer's and vascular dementia. The findings are particularly noteworthy given how common vitamin D deficiency is, affecting about twenty five percent of Americans and up to forty percent of Europeans. In this episode, we'll be discussing insights from Doctor. Scott Beach, who examines this significant study and its implications for our clinical practice.

作为本研究所教员的Beach医生将带我们审视这些证据，揭示这种简单经济的手段或可降低痴呆风险。提醒您：作为精神药理学研究所银卡或金卡会员，登录账户完成本期内容相关简短问卷即可获得0.5个继续医学教育学分。加入我们可每月获取超过两小时的精神药理学前沿更新，并解锁超过50小时的内容档案库。现在有请Beach医生——

Doctor. Beach, who serves on our faculty, will walk us through the evidence suggesting that this simple, affordable intervention might help reduce dementia risk. Remember that as silver or gold members of the Psychopharmacology Institute, you can earn 0.5 CME credits by logging into your account and answering a brief survey based on today's discussion. By joining the Psychopharmacology Institute, you gain access to over two hours of fresh psychopharmacology updates each month, plus immediate access to our extensive archive containing more than fifty hours of content. So now let's listen to Doctor.

为我们讲解维生素D与痴呆风险的关系。

Beach on vitamin D and dementia risk.

维生素及其他补充剂在预防阿尔茨海默病等神经退行性疾病中的作用正引发更多关注。近期一项小型研究中，包含ω-3脂肪酸、维生素B12、辅酶Q10、维生素C、益生菌和猴头菇等补充剂的激进生活方式干预被证实能延缓阿尔茨海默病进展。这些物质或已显示延缓认知衰退的益处，或存在相关理论依据。一项基于英国生物银行数据的新前瞻性队列研究进一步表明，维生素D可能影响包括阿尔茨海默病和血管性痴呆在内的主要神经认知障碍发展。

There is increased interest in the role that vitamins and other supplements may play in the prevention of neurodegenerative diseases, including Alzheimer's. In a recent small study in which drastic lifestyle changes were shown to slow the rate of progression of Alzheimer's disease, researchers included a variety of supplements in the regimen for patients in the intervention group. Omega three fatty acids, vitamin b twelve, coenzyme q, vitamin c, a probiotic, even lion's mane. All of these have either previously shown benefit at slowing cognitive decline or have theoretical reasons why they might be thought to do so. A new prospective cohort study using data from the UK Biobank adds to the growing evidence that vitamin d may also impact the development of major neurocognitive disorders, including Alzheimer's and vascular dementia.

我是Scott Beach，这里是精神药理学研究所《快讯》。这项新研究队列包含近27万名平均年龄62岁的受试者。近五分之一参与者存在维生素D缺乏（定义为<30nmol/L），超过三分之一存在不足（30-50nmol/L）。5%的受试者规律服用维生素D补充剂，20%服用含维生素D的复合维生素。补充剂使用者缺乏率显著降低。

I'm Scott Beach, and this is Quick Takes for the Psychopharmacology Institute. The new study cohort consisted of nearly 270,000 individuals with a mean age of 62 years. Nearly a fifth of participants showed signs of vitamin d deficiency, defined as less than 30 nanomoles per liter, while over a third showed vitamin d insufficiency, defined as levels between thirty and fifty. Five percent of the cohort reported regularly taking vitamin d supplements specifically, while twenty percent noted taking a multivitamin, most of which would contain vitamin d. Unsurprisingly, deficiency was much lower among users of a vitamin supplementation.

在13.5年随访期间，2.6%的参与者（约7000人）被新诊断为痴呆，其中约半数为阿尔茨海默病。经协变量调整后，维生素D缺乏/不足与痴呆（包括阿尔茨海默病和血管性痴呆）存在关联。最严格的分析显示：缺乏者痴呆风险增加25%，不足者增加11%。对于水平<50nmol/L者，存在剂量依赖关系。

Overall, two point six of participants or about seven thousand people were given a new dementia diagnosis during the follow-up period of thirteen and a half years. About half of these were given a diagnosis of Alzheimer's specifically. Vitamin D deficiency and insufficiency exhibited an association with dementia and with Alzheimer's and vascular dementias specifically, including when adjusting for covariates. In the most adjusted analysis, vitamin D deficiency was associated with a twenty five percent increased risk for dementia and insufficiency with an eleven percent increased risk. For individuals with levels less than 50, there appeared to be a dose dependent relationship.

按APOE基因型分析未发现统计学差异。值得注意的是：深色皮肤人群的维生素D水平与痴呆风险无显著关联（但该亚组分析可能统计效力不足）。最后，维生素D补充剂使用与较低阿尔茨海默病风险相关，这种相关性在55-64岁人群中尤为显著。我们该如何解读这些发现？

When analyzing by APOE gene type, no statistically significant differences emerged. One intriguing finding was that individuals with darker skin seemed to show no association between vitamin d levels and dementia risk, though it is important to note that this sub analysis may have been underpowered. Finally, in terms of vitamin d supplements, the authors also found that use of vitamin d supplements was associated with a lower risk of Alzheimer's. And this correlation was especially strong for younger individuals aged fifty five to sixty four years. So what do we make of this?

值得注意的是，这些英国生物银行研究之所以引人注目，是因为它们使用了前瞻性数据库，且统计效力通常很高。数据源丰富而详尽。该研究的作者在控制多种潜在混杂因素方面也做得非常出色，同时承认这终究是一项观察性研究，因此无法得出因果关系的结论。例如，那些认真服用维生素D补充剂的人可能也更倾向于服用多种其他补充剂，而真正影响痴呆症风险的可能是这些其他补充剂。另外值得注意的是，研究中患者的年龄偏小，处于我们预期痴呆症可能出现的年龄段之前，因此我们对例如九十岁高龄人群的痴呆症风险了解较少。

Well, these UK biobank studies are notable because they use a prospective database and they tend to be highly powered. The data source is rich and detailed. The authors of this study also do a very good job of controlling for multiple potential confounders, acknowledging that this is an observational study at the end of the day, so no conclusions can be drawn about causality. It's possible, for example, that individuals who are conscientious enough to take vitamin d supplements may also be more likely to take a variety of other supplements, and that it is actually these other supplements that impact the risk for development of dementia. Also worth noting is that patients in the study were on the younger side in terms of when we might expect dementia to present, so we don't know as much about the risk of dementia in the ninth decade, for example.

不过总体而言，这些结果进一步丰富了越来越多的文献，表明生活方式调整可能显著影响包括阿尔茨海默型和血管型在内的痴呆症风险。就维生素D而言，这些发现也与一些其他研究结果一致。作者指出，2019年的一项荟萃分析也发现，在维生素D水平低的状态下，阿尔茨海默症风险增加，效应估计值甚至更大。维生素D可能预防神经退行性变的机制尚不明确。先前的研究表明，它可能有助于分解β淀粉样斑块或防止淀粉样蛋白诱导的神经元凋亡。

Overall, though, the results add to the growing body of literature suggesting that lifestyle modifications may significantly impact the risk of developing dementia, including Alzheimer's and vascular types. In terms of vitamin d specifically, the findings are also consistent with some other studies. The authors note that a 2019 meta analysis also found an increased risk of Alzheimer's in low vitamin d states with even larger effect estimates. The mechanism through which vitamin D may prevent neurodegeneration remains unclear. Previous research has suggested that it may help to break down beta amyloid plaques or prevent amyloid induced neuronal apoptosis.

有些人怀疑维生素D还可能防止tau蛋白过度磷酸化。维生素D缺乏极为常见，在美国高达四分之一的人群中存在，在欧洲则高达百分之四十。这是合理的，因为维生素D主要通过阳光照射获得，因此生活在高纬度地区的人缺乏风险更高。维生素D也可以通过饮食获取，特别是通过食用鳟鱼或鲑鱼、白蘑菇、牛奶和大豆等食物。值得注意的是，肥胖是维生素D缺乏的重要风险因素，因为维生素D代谢物会被脂肪组织隔离。

Some suspect vitamin d may also protect against tau hypophosphorylation. Vitamin d deficiency is extremely common occurring in up to a quarter of individuals in The US and up to forty percent of Europeans. This makes sense because vitamin d is most commonly obtained through exposure to sunlight, so those living at higher latitudes are at higher risk for deficiency. Vitamin d can also be obtained through diet, particularly by eating foods like trout or salmon, white mushrooms, milk, and soy. Notably, obesity is a significant risk factor for vitamin d deficiency due to sequestration of vitamin d metabolites in adipose tissue.

鉴于低维生素D水平与其他神经精神问题（包括抑郁、焦虑甚至精神分裂症）有关，这项研究很好地提醒我们，可能值得检查患者的维生素D水平，特别是中老年患者。我们在住院会诊服务中已经开始常规进行这项检查。对于被发现维生素D不足或缺乏的患者，应提供补充剂，并告知低维生素D水平对心理和身体健康（包括可能增加的神经退行性疾病风险）的潜在影响。

Given that low vitamin d levels have been linked to other neuropsychiatric issues, including depression, anxiety, and even schizophrenia, this study serves as a good reminder that it may be worth checking levels in our patients, particularly in middle aged and older patients. It's something we've started doing pretty routinely on the inpatient consultation service. Patients found to be insufficient or deficient should be offered supplementation and counseled about the potential impact of low vitamin d levels on mental and physical health, including the possible increased risk for neurodegenerative illness.

这是Beach医生在讨论英国生物银行一项关于维生素D水平与痴呆症风险潜在关系的有力证据。这项大规模研究涉及近27万人，发现维生素D缺乏与痴呆症风险增加25%相关，而维生素D不足则与风险增加11%相关。那么回到我们的患者Johnson女士，你会采取什么方法？基于这些证据，你可能会将维生素D检测纳入她的预防性检查中。

That was doctor Beach discussing the compelling evidence from a UK Biobank study on the potential relationship between vitamin D levels and dementia risk. This large scale study of nearly 270,000 individuals found that vitamin D deficiency was associated with a 25 increased risk for dementia, while vitamin D insufficiency correlated with an eleven percent increased risk. So circling back to our patient Mrs. Johnson, what approach would you take? Well, based on this evidence, you may include vitamin D testing as part of her preventative workup.

如果她属于那四分之一的缺乏维生素D的美国人或更多不足的人群，补充维生素D是一种低风险干预措施，可能带来显著益处。你可以向她解释，维生素D可能有助于多种神经保护功能，从可能帮助分解有害的淀粉样斑块到防止tau蛋白异常过度磷酸化，保护神经元免于过早死亡。Beach医生讨论的关键点强调，这不仅仅是相关性噪音。这种关系似乎是剂量依赖性的，维生素D水平越低，痴呆症风险越高。

If she's among the quarter of Americans with deficiency or the many more with insufficiency, supplementation represents a low risk intervention with potentially significant benefits. You might explain to her that vitamin D may help with various neuroprotective functions, from potentially assisting in breaking down harmful amyloid plaques to preventing the abnormal hyperphosphorylation of tau proteins, protecting neurons from premature death. The key points from Doctor. Beach's discussion highlight that this isn't just correlational noise. The relationship appears dose dependent, with lower vitamin D levels correlating with higher dementia risk.

该研究控制了许多潜在的混杂因素，与先前的研究（包括2019年一项发现更强关联的荟萃分析）一致。特别引人注目的是，补充维生素D与较低的阿尔茨海默症风险相关，尤其是在55至64岁的较年轻患者中。这表明早期干预可能有潜在益处，当然我们还需要更多的随机试验。我还会提醒Johnson女士，这只是全面脑健康方法的一部分。

The study controlled for numerous potential confounding factors in alliance with previous research, including a 2019 meta analysis that found even stronger associations. What's particularly compelling is that vitamin D supplementation was associated with a lower Alzheimer's risk, especially in younger patients aged 55 to 64. This suggests potential benefits to early intervention, though of course we need more randomized trials here. I would also remind Mrs. Johnson that this is just one piece of a comprehensive approach to brain health.

维生素D筛查简单直接，补充剂价格低廉，潜在的收益风险比是有利的。你也可以讨论富含维生素D的饮食来源，如鲑鱼和鳟鱼等脂肪鱼、蘑菇、强化牛奶和大豆制品，同时解释阳光照射仍然是我们最高效的天然来源。如果你喜欢收听今天的节目，请通过在Apple Podcasts上留下评论帮助我们触达更多像你一样的临床医生。对于我们的银牌和金牌会员，别忘了你可以通过登录你的账户并完成简短的评估来获得这次Quick Take的CME学分。非常感谢你今天加入我。

The vitamin D screening is straightforward, the supplements are inexpensive, and the potential benefit to risk ratio is favorable. You also may discuss dietary sources rich in vitamin D, fatty fish like salmon and trout, mushrooms, fortified milk, and soy products, while explaining that sunlight exposure remains our most efficient natural source. If you enjoyed listening to today's episode, please help us reach more clinicians like yourself by leaving a review on Apple Podcasts. And for our Silver and Gold members, don't forget that you can earn CME credits for this Quick Take by logging into your account and completing the brief assessment. I'd like to thank you very much for joining me today.

我是Richard Sieber医生，期待在下一期节目中见到你。再见。

This is Doctor. Richard Sieber, and I look forward to seeing you in our next episode. Bye now.