我已經差不多八十五歲了，近兩年我覺得思維有大改變，有時忘掉別人的名字，有時措辭不適當。我是醫生，我覺得不像阿茲海默症。剛看文獻，覺得與「邊緣系統主導型遺忘性神經退化性綜合症(LANS)」有關。(圖一和二)

 

I am almost 85 years old, and over the past two years, I have noticed significant changes in my thinking. Sometimes I forget people’s names, and other times my wording is in appropriate. I am a doctor, and I feel it is not like Alzheimer’s disease. After reading some literatures, I believe it may be related to “Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS). (Figure 1 and 2)

 

邊緣系統主導型遺忘性神經退化性綜合症(LANS)是一種新定義的記憶喪失類型，主要影響大腦的邊緣系統。由於症狀類似，這種綜合症經常被誤認為阿茲海默症，但其進展較慢且預後更好。該病症以顯著的情景記憶損害為特徵，而其他認知功能大體上保持完整 (Mayo Clinic News Network)(SciTechDaily) 。

 

            Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS) is a newly defined type of memory loss that primarily affects the limbic system in the brain. This syndrome is often mistaken for Alzheimer’s disease due to similar symptoms but has a slower progression and better prognosis. The condition is characterized by predominant impairment of episodic memory while other cognitive functions remain largely intact. (Mayo Clinic News network) (SciTechDaily)

 

LANS與邊緣系統中TDP-43蛋白的積聚有關，這一點區別於阿茲海默症，後者更常見的特徵是tau蛋白和澱粉樣斑塊的積聚。診斷LANS的標準包括年齡、記憶損害的嚴重程度、大腦掃描以及特定生物標誌等因素。(Oxford Academic)(Neuroscience News)

 

LANS has been associated with the build-up of a protein called TDP-43 in the limbic system, which differentiates it from Alzheimer’s, where tau proteins and amyloid plaques are more common. The criteria for diagnosing LANS involve factors such as age, severity of memory impairment, brain scans, and specific biomarkers. (Oxford Academic) (Neuroscience News)

 

理解和診斷LANS非常重要，因為這能夠讓患者獲得更精確的治療和症狀管理，提供更針對性的療法。這些標準的建立是區分LANS與其他神經退行性疾病的重要一步，為受影響的患者帶來更好的臨床結果。(Mayo Clinic News Network) (SciTRechDaily)

 

Understanding and diagnosing LANS is crucial as it allows for more precise treatment and management of symptoms, offering better-tailored therapies for patients. The establishment of these criteria marks a significant step in distinguishing LANS from other neurodegenerative conditions, leading to improved clinical outcomes for those affected. (Mayo Clinic News Network) (SciTechDaily)

 

邊緣系統主導型遺忘性神經退化性綜合症（LANS）有特定的臨床特徵，有助於識別和區分其與其他神經性退行性疾病（如阿茲海默症）。以下是主要的臨床特徵：

1.    記憶障礙

·         主要表現為情景記憶的顯著損害，即回憶個人經歷和具體事件的能力。

·         其他認知領域（如語言和執行功能）在早期階段相對保留。(Mayo Clinic New Network) (ScienceDaily)

2.    緩慢進展

·         LANS的臨床進展通常比阿茲海默症慢。患者可能在較長時間內僅表現出記憶喪失，而其他認知功能未顯著惡化。(Neurology Live)

3.    發病年齡

·         LANS更常見於老年人，通常發病於70歲末至80歲，年輕人較少見。（Neurology live）

4.    腦部影像學發現

·         MRI或 CT掃描通常顯示海馬體和邊緣系統其他部位的顯著萎縮。這與阿茲海默症中的廣泛大腦萎縮形成對比。（Mayo Clinic News Network）(Neurology Live)

5.    生物標誌物

·         邊緣系統中TDP-43蛋白沉積的存在，通過腦脊液(CSF)分析或死後檢查確定。這些蛋白沉積較少與tau蛋白或澱粉樣斑相關，而這些蛋白沉積在阿茲海默症中更為常見。(Neurology Live) (ScienceDaily)

6.    神經心理學特徵

·         神經心理學測顯示情景記憶顯著缺損，而語義記憶（有關世界的常識）和其他認知功能在疾病初期相對完整。（ScienceDaily）

7.    缺乏新皮質參與

·         在早期階段，通常缺乏顯著的新皮質退化，這有助於區分LANS與涉及廣泛皮質萎縮的其他形式癡呆。(Mayo Clinic News Network) (Neurology Live)

 

這些臨床特徵為醫療提供者提供了一個診斷LANS的框架，使他們能夠更準確地

診斷並更好地管理者種病症。理解這些特徵還有助於將LANS與其他類似的神經退行性疾病區分開來。(Mayo Clinic News Network) (Neurology Live) (ScienceDaily)

 

Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS) has specific clinical characteristics that help in its identification and differentiation from other neurodegenerative conditions such as Alzheimer’s disease. Here are the key clinical characteristics:

1.    Memory Impairment

·         Predominant impairment of episodic memory, which is the ability to recall personal experiences and specific events.

·         Other cognitive domains, such as language and executive functions, are relatively preserved in the early stages. (Mayo Clinic News Network) (ScienceDaily)

2.    Slow Progression

·         LANS typically has a slower clinical progression compared to Alzheimer’s disease. Patients may experience memory loss over a longer period without significant deterioration in other cognitive areas. (Neurology Live)

3.    Age of Onset

·         LANS is more commonly diagnosed in older adults, often those in their late 70s and 80s. It is less likely to occur in younger individuals. (Mayo Clinic News Network)

4.    Brain Imaging Findings

·         MRI or CT scans typically show disproportionate atrophy of the hippocampus and other parts of the limbic system. This contrasts with the more widespread brain atrophy seen in Alzheimer’s disease. (Mayo Clinic News Network) (Neurology Live)

5.    Biomarkers

·         Presence of TDP-43 protein deposits in the limbic system, identified through cerebrospinal fluid (CSF) analysis or postmortem examination. These protein deposits are less commonly associated with tau proteins or amyloid plaques, which are more characteristic of Alzheimer’s disease. (Neurology Live) (ScienceDaily)

6.    Neuropsychological Profile

·         Neuropsychological tests indicate significant deficits in episodic memory while semantic memory (general knowledge about the world) and other cognitive functions remain relatively intact during the initial stages of the disease. (ScienceDaily)

7.    Absence of Neocortical Involvement

·         In the early stages, there is typically an absence of significant neocortical degeneration, which helps differentiate LANS from other forms of dementia that involve extensive cortical atrophy. (Mayo Clinic News Network) (Neurology Live)

 

These clinical characteristics provide a framework for healthcare providers to

diagnose LANS accurately, enabling more precise treatment and management of the condition. Understanding these features also aids in differentiating LANS from other similar neurodegenerative disorders. (Mayo Clinic News Network) (Neurology Live) (ScienceDaily)

 

 

目前，尚無針對邊緣系統主導型遺忘性經退化性綜合症(LANS)的特定治療方法。然而，建立新的診斷標準有助於區分LANS與阿茲海默症，這對治療決策具有重要意義。研究人員建議，理解和識別LANS可以導致更好的症狀管理和更針對性的療法。

 

潛在的治療方法可能包括：

1.    目標治療：由於LANS涉及邊緣系統中TDP-43蛋白的積聚，未來可能會開發針對這種蛋白的治療方法。

2.    症狀管理：與其他神經退化性疾病類似，通過認知療法、生活方式改變和支持性護理來管理症狀可以提高生活質量。

3.    臨床試驗：隨著LANS被更清晰地定義，特定於此疾病的新臨床試驗可能會出現，重點關注可以減緩其進展或緩解症狀的新治療方法。

 

診斷LANS的標準包括年紀、記憶損害的嚴重程度、大腦掃描和生物標誌等因素，這可以幫助醫療提供者更精確的診斷並探索潛在的治療方法。(Mayo Clinic News Network) (Neurology Live) (Science Daily)

 

Currently, there is no specific treatment for Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS). However, the establishment of new diagnostic criteria helps distinguish LANS from Alzheimer’s disease, which has implications for treatment decisions. Researchers suggest that understanding and identifying LANS can lead to better management of symptoms and more tailored therapies.

 

Potential treatment approaches may include:

1.    Targeted Therapies: Since LANS involves the buildup of the TDP-43 protein in the limbic system, treatments targeting this protein might be developed in the future.

2.    Symptom management: Similar to other neurodegenerative conditions, managing symptoms through cognitive therapies, lifestyle changes, and supportive care can improve quality of life.

3.    Clinical trials: As LANS is more clearly defined, new clinical trials specific to this condition may become available, focusing on treatments that could slow its progression or alleviate symptoms.

 

The criteria for diagnosing LANS involve factors such as age, memory impairment severity, brain scans, and biomarkers, which can help healthcare providers offer more precise diagnoses and explore potential treatment. (Mayo Clinic News Network) (Neurology Live) (ScienceDaily)

 

以下是一些被研究用於管理與TDP-43蛋白病變(如邊緣系統主導型遺忘性神經退

化綜合症（LANS）和肌萎縮性脊髓側索硬化症(ALS)相關病症的補充劑和化合物概述：

1.    維生素B12

·         作用和好處：維生素B12對維持健康的神經細胞和生產DNA 和RNA至關重要。它具有神經保護特性，可能有助於減少神經炎症並支持認知功能。(Nature) (Fight Aging!)

·         研究：一些研究表明，B12缺乏會加劇神經症狀，補充B12可能改善結果，儘管對其TDP-43蛋白病變的直接影響證據有限。

2.    小檗鹼

·         作用和好處：小檗鹼是一種存在於多種植物中的生物鹼，具有抗炎和抗氧化特性。已知它可以改善線粒體功能並減少氧化壓力，這可能對神經退化性疾病有益。(Fight Aging!)

·         研究：小檗鹼對TDP-43積聚的影響證據有限，但其一般的的神經保護作用可能提供間接好處。

3.    依達拉奉

·         作用和好處：依達拉奉是一種自由基清除劑，已被批准用於治療ALS。它有助於減少氧化壓力，這視神經退化性疾病的一個關鍵因素。(SpringerLink)(Fight Aging!)

·         研究：研究表明，依達拉奉可以減慢ALS的進展，其減少氧化壓力的作用可能有助於緩解TDP-43蛋白病變的影響。

4.    伽馬氨基丁酸(GABA)

·         作用和好處：GABA是一種抑制神經傳遞的大腦神經遞質，有助於平靜神經活動，它通常用於減少焦慮並改善睡眠。

·         研究：雖然GABA對TDP-43的直接影響尚未有詳細記錄，但其對神經系統的整體鎮靜作用可能有助於管理與神經退化性疾病相關的症狀。(Nature)(BioMed Central)

 

潛在的好處總結

·         維生素B12:支持神經健康和認知功能。

·         小檗鹼：提供抗炎和抗氧化益處。

·         依達拉奉：減少氧化壓力，有益於ALS。

·         GABA:鎮靜神經系統，可能有助於管理神經退化性症狀。

 

需要更多研究

儘管這些化合物顯示出潛力，但需要更多研究來確立它們在直接應對TDP-43蛋白病變方面的有效性。在開始任何新的補充劑之前，尤其是管理像LANS和ALS這樣的複雜病症，建議諮詢醫療提供者。

 

如需更多詳細資訊，可以參考以下來源：

·         Neurotherapeutics on TDP-43 (SpringerLink)

·         Nature on TDP-43 Proteinopathy (Nature)

·         Fight Aging on Reducing TDP-43 Proteinopathy (Fight Aging!)

Several supplements and compounds are being explored for their potential benefits in managing conditions associated with TDP-43 Proteinopathy, such as Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS) and amyotrophic lateral sclerosis (ALS). Here is an overview of some of these compounds:

1.     Vitamin B12:

·         Role and benefits: Vitamin B12 is essential for maintaining healthy nerve cells and producing DNA and RNA. It has neuroprotective properties and may help in reducing neuroinflammation and supporting cognitive function. (Nature) (Fight Aging!)

·         Research: Some studies suggest that B12 deficiency can exacerbate neurological symptoms and supplementation might improve outcomes, though direct evidence on its effect on TDP-43 Proteinopathy is limited.

2.    Berberine:

·         Role and Benefits: Berberine is an alkaloid found in various plants with anti-inflammatory and antioxidant properties. It is known to improve mitochondrial function and reduce oxidative stress, which might be beneficial in neurodegenerative conditions. (Fight Aging!)

·         Research: There is limited direct evidence on berberine’s impact on TDP-43 accumulation, but its general neuroprotective effects could offer indirect benefits.

3.    Edaravone:

·         Role and Benefits: Edaravone is a free radical scavenger approved for treating ALS. It helps reduce oxidative stress, which is a key factor in neurodegenerative diseases. (SpringerLInk) (Fight Aging!)

·         Research: Studies have shown that Edaravone can slow the progression of ALS, and its role in reducing oxidative stress might help mitigate the effects of TDP-43 proteinopathy.

4.    Gamma-Aminobutyric Acid (GABA):

·         Role and Benefits: GABA is a neurotransmitter that inhibits nerve transmission in the brain, calming nervous activity. It is commonly used to reduce anxiety and improve sleep.

·         Research: While GABA’s direct effect on TDP-43 are not well-documented, its overall calming effects on the nervous system may help manage symptoms associated with neurodegenerative conditions. (Nature( (BioMed Central)

 

Summary of Potential Benefits

·         Vitamin B12: Supports nerve health and cognitive function.

·         Berberine: Offers anti-inflammatory and antioxidant benefits.

·         Edaravone: Reduces oxidative stress, beneficial in ALS.

·         GABA: Calms the nervous system and may help manage neurodegenerative symptoms.

 

Additional Research Needed

While these compound show promise, more research is needed to establish their

efficacy in directly addressing TDP-43 proteinopathy. It is advisable to consult with a healthcare provider before starting any new supplement, especially for managing complex conditions like LANS and ALS.

 

          For more detailed information, you can refer to:

 

•   ````````Neurotherapeutics on TDP-43 (SpringerLink)

·         Nature on TDP-43 Proteinopathy (Nature)

·         Fight Aging on Reducing TDP-43 Proteinopathy (Fight Aging!)

 

 

圖一

Figure 1

 

腦部退化病示圖

Schematic of Brain Degeneration and Pathology

 

圖二

Figure 2

黃思賢

Shi-Yin Wong

 

8/1/2024