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維生素B6與維生素D缺乏會影響記憶力嗎？本文從銀髮族記憶門診研究出發，解析B6、D缺乏與認知功能、MMSE分數的關聯。
當家人開始出現記憶力變差、重複問同樣的問題、常常忘記東西放在哪裡，或是原本可以處理的事情變得比較吃力時，許多人第一個擔心的是：「是不是失智症？」
這個擔心很合理，因為隨著年齡增加，阿茲海默症、血管型失智症、輕度認知障礙等問題確實變得更常見。
但在真正進入「失智症」或「阿茲海默症」這些診斷之前，有一件事常常被忽略：銀髮族的記憶力與認知功能，不只和大腦退化有關，也可能和營養狀態、睡眠、發炎、慢性疾病、藥物使用、情緒狀態與生活功能有關。
其中，維生素B12常常會被醫師檢查，因為B12缺乏可能造成貧血、神經病變，也可能影響認知功能。不過，除了B12之外，維生素B6與維生素D也可能和銀髮族的大腦功能有關。近年一篇發表於 Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring 的研究，就特別觀察了記憶門診高齡患者中，維生素B6與維生素D缺乏是否常見，以及這些缺乏是否和認知表現有關。研究發現，在記憶門診銀髮患者中，維生素B6缺乏與維生素D缺乏都相當常見，而且兩者缺乏常常同時出現；更重要的是，這些缺乏和較低的MMSE認知篩檢分數有關。
這不代表「補充維生素B6或維生素D就能治療失智症」，但它提醒我們：當長輩出現記憶力下降時，除了擔心大腦退化，也應該回頭檢視身體是否存在可調整、可補足的營養問題。
為什麼銀髮族記憶力下降，不能只看「大腦退化」？
為什麼銀髮族記憶力下降，不能只看「大腦退化」？
很多人一聽到記憶力變差，就會直接聯想到阿茲海默症。阿茲海默症確實是重要的神經退化性疾病，年齡也是最大的危險因子之一。但臨床上，記憶力下降常常不是單一原因造成，而是多個因素累積的結果。
例如，有些長輩睡眠品質很差，夜間頻尿、打呼、半夜醒來、白天嗜睡，長期下來注意力和短期記憶都會受到影響。
有些長輩長期食慾不好，蛋白質攝取不足，B群或維生素D缺乏，身體能量代謝下降，也可能讓精神、反應與認知表現變差。
有些長輩同時服用多種藥物，部分藥物可能影響注意力、平衡、睡眠或精神狀態。
有些人則是因為憂鬱、焦慮、喪偶、社交減少，使得看起來像記憶力退步，其實背後有情緒與生活脈絡的因素。
因此，面對銀髮族記憶力變差時，除了評估是否有失智症，也應該同步檢查是否有可逆或可改善的因素。營養素缺乏就是其中一個容易被忽略、但值得重視的面向。
這篇研究在問什麼問題？
這篇研究在問什麼問題？
這篇研究是一項回溯性橫斷面病歷回顧，研究對象是美國威斯康辛大學記憶評估門診的高齡患者。研究者回顧了203位新患者的資料，其中有164位在看診當天接受一種或多種維生素檢測。研究觀察的維生素包括維生素B1、B6、B12與維生素D，並同時記錄MMSE，也就是Mini-Mental State Examination，作為基本認知功能篩檢分數。
這篇研究的目的，不是證明某一種維生素可以治療失智，而是想知道：在記憶門診的高齡患者中，哪些維生素缺乏比較常見？維生素B6與維生素D缺乏會不會一起出現？這些缺乏是否和認知篩檢分數有關？
這個問題很重要。因為在許多記憶門診中，B12通常會被例行檢查，但B6、B1、D不一定會被常規評估。研究者也指出，雖然B12是記憶門診和研究中常被檢測的營養素，但其他對中樞神經系統有意義的維生素，例如B6、B1與D，並不一定會被例行檢查。
換句話說，這篇研究想提醒的是：我們會不會太習慣只看B12，而忽略了B6與D？
研究發現一：維生素B6缺乏很常見，甚至比B12更常見
研究發現一：維生素B6缺乏很常見，甚至比B12更常見
這篇研究最讓人注意的結果之一，是在這群記憶門診高齡患者中，維生素B6缺乏是最常見的缺乏項目。
研究中，128位患者接受維生素B6檢測，其中48位被判定為缺乏，比例為37.5%。相比之下，維生素B12缺乏的比例為17.2%，明顯低於B6。維生素D缺乏則為36.8%，也相當常見。
這個發現值得注意，因為一般人談到記憶力與營養時，最常想到的是B12。B12當然重要，但這篇研究顯示，在記憶門診族群中，B6缺乏可能並不少見，甚至可能比B12缺乏更常出現。
這代表什麼？
它不代表每一位記憶力退化的長輩都一定缺B6，也不代表補B6就能改善所有認知問題。但它提醒臨床工作者與照顧者：如果長輩已經出現記憶力下降、精神反應變慢、注意力變差，除了檢查B12，也可以思考是否需要評估B6與D等其他營養狀態。
尤其對於食慾差、飲食單調、長期外食、咀嚼困難、腸胃吸收不佳、慢性疾病多、活動量低、日曬不足的長輩來說，營養素缺乏可能不是少數情況。
研究發現二：維生素B6與維生素D缺乏常常一起出現
研究發現二：維生素B6與維生素D缺乏常常一起出現
這篇研究另一個重點，是維生素B6與維生素D缺乏之間有顯著共現關係。
在同時檢測B6與D的96位患者中，有27位同時缺乏維生素B6與維生素D，占28.1%。研究者進一步分析後發現，B6缺乏與D缺乏之間有顯著關聯；如果其中一種維生素缺乏，另一種也缺乏的風險明顯提高，勝算比約為6.91。
這個結果有趣的地方在於，維生素B6和維生素D本來是性質很不同的營養素。維生素B6是水溶性維生素，常見於多種食物中，參與胺基酸代謝與神經傳導物質合成。維生素D則是脂溶性維生素，和日曬、骨骼、免疫調節、發炎反應都有關。
兩者來源不同、代謝特性不同，卻在記憶門診高齡患者中出現明顯共缺乏，這可能代表幾件事。
第一，這可能反映整體營養狀態不佳。
如果一位長輩飲食單調、食量下降、活動量少、曬太陽不足，就可能不是只缺一種營養素，而是多種營養素一起不足。
第二，這可能反映身體功能下降。
記憶力變差的長輩可能外出減少、煮飯能力下降、生活節奏混亂，進而導致飲食與日曬都變差。這時營養缺乏可能既是結果，也可能反過來加重身體與認知功能下降。
第三，這可能提示臨床評估不能只看單一指標。
如果檢查發現長輩缺乏維生素D，也許不應只補D就結束，而可以進一步思考B6、B12、蛋白質、貧血、甲狀腺、腎功能、發炎狀態等是否也需要評估。
研究發現三：B6與D缺乏和較低MMSE分數有關
研究發現三：B6與D缺乏和較低MMSE分數有關
這篇研究最重要的臨床意義，是維生素B6與維生素D缺乏都和較低的MMSE認知篩檢分數有關。
研究中，沒有B6與D缺乏的人，平均MMSE分數約為26分；而同時缺乏B6與D的人，平均MMSE分數約為23.04分，兩者差異達統計顯著。
MMSE是一種常見的認知功能篩檢工具，用來初步評估定向感、記憶、注意力、計算、語言與執行能力等面向。分數較低不一定代表就是失智症，因為教育程度、語言、情緒、聽力、視力與身體狀態都可能影響表現。但在記憶門診中，MMSE仍然是臨床上常用的基礎評估工具。
因此，當研究發現B6與D缺乏者MMSE較低時，這不代表缺乏一定造成認知退化，但代表兩者之間可能存在值得重視的關聯。
比較穩健的解讀應該是：
在記憶門診高齡患者中，維生素B6與維生素D缺乏與較差的認知篩檢表現有關，因此在評估記憶力下降時，這些營養素可能值得納入檢查與追蹤。
維生素B6為什麼可能和記憶力有關？
維生素B6為什麼可能和記憶力有關？
維生素B6之所以可能和認知功能有關，主要是因為它參與多種和神經系統相關的生化反應。
研究文章指出，維生素B6是合成多種神經傳導物質所需要的營養素，包括血清素、正腎上腺素、腎上腺素與GABA。這些神經傳導物質和情緒、注意力、睡眠、警醒程度、神經興奮與抑制平衡都有關。
從臨床角度來看，記憶力並不是單純「海馬迴能不能記住」而已。注意力、睡眠品質、情緒穩定、精神清明度、反應速度，都是記憶表現的一部分。
如果一個人長期睡不好、情緒低落、白天昏沉、神經系統調節能力下降，他在認知測驗中的表現也可能受到影響。
維生素B6也和同半胱胺酸代謝有關。B群狀態不佳時，同半胱胺酸可能升高，而同半胱胺酸過高被認為和血管健康、腦部功能與認知退化風險有關。雖然這篇研究主要聚焦在B6與D缺乏共現和MMSE分數，但把B6放在整體神經代謝與血管代謝的脈絡中理解，是合理的。
不過，這裡仍然要避免過度簡化。大腦功能是多因素共同影響的結果，B6只是其中一個可能相關的營養因子，不應被單獨神化。
維生素D為什麼可能和大腦功能有關？
維生素D為什麼可能和大腦功能有關？
維生素D最常被大家聯想到骨質疏鬆、骨折、肌力不足與免疫功能，但近年也有越來越多研究討論維生素D與大腦健康、認知功能、情緒和發炎之間的關係。
這篇研究在討論中提到，過去研究曾發現輕度認知障礙與阿茲海默症患者的血清維生素D濃度顯著低於健康對照組；也有研究指出維生素D受體基因多型性與阿茲海默症有關。此外，維生素D也可能透過調節促發炎狀態、影響類澱粉蛋白負荷與免疫細胞吞噬作用，參與大腦健康相關機制。
對銀髮族來說，維生素D不足非常常見。原因包括日曬不足、戶外活動減少、皮膚合成能力下降、飲食攝取不足、腎臟活化能力下降、慢性疾病與藥物影響等。
維生素D不足不只可能影響骨骼，也可能和肌力下降、跌倒風險、慢性疼痛、情緒低落、免疫功能與發炎狀態有關。這些因素又會進一步影響長輩的活動量、睡眠、社交與認知刺激，形成一個互相牽動的循環。
所以，當長輩記憶力下降時，維生素D檢查不應只被視為「骨頭問題」，也可以放進整體老年健康與認知功能評估中一起看。
這篇研究不能告訴我們什麼？
這篇研究不能告訴我們什麼？
雖然這篇研究很有啟發性，但它也有明確限制。
第一，這是一項橫斷面回溯性研究，因此不能推論因果。
也就是說，我們不能說「因為缺乏B6與D，所以導致MMSE變低」。也有可能是認知功能下降後，飲食變差、外出減少、生活自理能力下降，才導致B6與D缺乏。兩者也可能受到第三個因素影響，例如慢性病、活動量、營養不良或社會支持不足。
第二，研究對象主要來自特定記憶門診，且族群多樣性有限。
研究中受試者大多為白人，因此結果不一定能完全套用到台灣或亞洲高齡族群。不同地區的飲食型態、日曬習慣、補充品使用、醫療評估流程與生活方式都不同。
第三，研究使用MMSE作為認知篩檢指標，但MMSE不是完整神經心理測驗。
MMSE可以提供基礎參考，但無法細緻區分記憶、執行功能、語言、視空間、處理速度等不同認知領域。若要更精準評估認知功能，仍需要完整的臨床評估與必要時的神經心理檢查。
第四，維生素B6檢測最好在空腹狀態下進行，但這篇研究並未要求患者空腹。
研究者也承認，這可能影響B6檢測結果。不過研究者認為，由於他們主要關心缺乏而不是毒性，這可能反而低估了B6缺乏的比例。
因此，這篇研究的價值不是給出最終答案，而是提出一個很實際的提醒：在記憶門診與銀髮族認知評估中，B6與D可能值得更常被檢查。
長輩記憶力變差，哪些營養與身體狀況可以一起評估？
長輩記憶力變差，哪些營養與身體狀況可以一起評估？
如果家人開始出現記憶力下降，除了安排醫師評估是否有輕度認知障礙或失智症，也可以同步整理以下幾個面向：
第一，飲食是否變少或變單調。
長輩是否常常只吃白飯、麵、稀飯？蛋白質是否足夠？蔬菜、豆類、魚肉、蛋奶是否攝取穩定？如果牙口不好、吞嚥困難或煮飯能力下降，營養不足會更容易發生。
第二，是否缺乏日曬與活動。
長期待在室內、怕跌倒不出門、活動量下降，都可能增加維生素D不足與肌力下降的風險。活動量下降也會讓睡眠與情緒變差，間接影響認知功能。
第三，睡眠是否穩定。
若長輩夜間睡不好、白天昏沉、打呼嚴重、常常半夜醒來，認知表現可能受到很大影響。睡眠問題和記憶力下降常常互相加重。
第四，是否有憂鬱或焦慮。
銀髮族憂鬱有時不會明顯表現為「心情不好」，而是出現不想動、食慾下降、記憶變差、反應變慢、睡眠變差。這種情況需要被辨識，而不是單純歸因於老化。
第五，是否有藥物影響。
鎮靜安眠藥、抗膽鹼藥物、部分止暈藥、止痛藥、過敏藥或多重用藥，都可能影響精神狀態、記憶力、平衡與跌倒風險。
第六，是否有可檢查的營養或代謝問題。
除了B12之外，B6、D、B1、葉酸、甲狀腺功能、貧血、腎肝功能、血糖控制、電解質等，都可能在不同情境下納入評估。
可以自行補充維生素B6和D嗎？
可以自行補充維生素B6和D嗎？
很多人看到「B6與D缺乏和認知分數有關」，第一個反應就是：那是不是趕快買B群和維生素D給長輩吃？
這個想法可以理解，但不建議完全自行長期高劑量補充。
維生素D是脂溶性維生素，長期過量可能造成高血鈣、腎臟負擔與其他問題。維生素B6雖然是水溶性維生素，但長期高劑量補充也可能造成周邊神經相關副作用，例如麻木、刺痛或感覺異常。因此，補充前最好先了解是否真的缺乏、缺乏程度如何，以及長輩是否有腎功能問題、慢性病或正在服用其他藥物。
比較安全的做法是：
如果長輩已經有記憶力下降、食慾不佳、活動量低、日曬不足或慢性病，建議由醫師評估是否需要抽血檢查。若確認缺乏，再依照檢驗數值與身體狀況調整補充劑量與追蹤時間。
營養補充的目標不是「越多越好」，而是回到適當範圍。尤其在銀髮族身上，過度補充和不足一樣，都可能帶來問題。
從中醫與整合照護角度看：記憶力下降是全身狀態的訊號
從中醫與整合照護角度看：記憶力下降是全身狀態的訊號
從中醫臨床角度來看，長輩記憶力下降通常不會只被視為單一腦部問題，而是會一起觀察睡眠、飲食、氣血、痰濕、腎精、情志、活動力與生活節律。
有些長輩是氣血不足，表現為疲倦、臉色差、精神不集中、健忘、睡眠淺。
有些長輩是痰濕較重，表現為頭重、昏沉、白天想睡、胸悶、胃脹、舌苔厚。
有些長輩是肝鬱化火或陰虛火旺，表現為煩躁、睡不著、早醒、口乾、夜間不安。
有些長輩則是腎精不足，逐漸出現腰膝痠軟、耳鳴、夜尿、記憶力下降與整體退化。
現代營養評估中的B6、D、B12、蛋白質、貧血與代謝狀態，可以和中醫辨證互相補充。前者幫助我們看見具體可測量的生理指標，後者幫助我們理解身體功能如何整體失衡。
對照顧者來說，最重要的不是急著把記憶力下降歸類為某一個診斷，而是把長輩最近的變化完整記錄下來。包括什麼時候開始變差、是突然變差還是慢慢變差、是否感染後明顯退步、是否跌倒或頭部外傷後退步、是否睡眠改變、食慾改變、情緒改變、藥物改變。這些細節對醫師判斷非常重要。
結論：記憶力下降時，B6與D值得被看見，但不是唯一答案
結論：記憶力下降時，B6與D值得被看見，但不是唯一答案
這篇記憶門診研究提醒我們，在高齡記憶力下降的族群中，維生素B6與維生素D缺乏都相當常見，而且兩者常常一起出現。研究也發現，B6與D缺乏和較低的MMSE認知篩檢分數有關。這些結果支持一個很實際的觀點：當銀髮族出現記憶力變差時，營養狀態不應被忽略。
不過，這篇研究不能證明補充B6或D可以治療失智症，也不能取代完整的臨床診斷。它比較像是一個提醒：在評估記憶力下降時，我們不應只看大腦影像或單一失智診斷，也應該檢視可改善的身體條件，包括營養缺乏、睡眠、情緒、活動力、慢性疾病與藥物影響。
對家屬而言，如果長輩近期出現記憶力下降、反應變慢、白天昏沉、走路變少、食慾下降或生活功能改變，建議不要只自行購買保健食品，而是尋求醫師評估。透過完整檢查與生活紀錄，找出哪些因素是退化本身，哪些因素是可以改善的身體狀態。
記憶力下降不一定只有一個原因。
有些變化來自大腦退化，有些變化來自身體失衡。
把可調整的因素找出來，對長輩與照顧者來說，往往就是最重要的第一步。
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Alzheimers Dement (Amst). 2024 Jan 22;16(1):e12525. doi: 10.1002/dad2.12525
Vitamin B6 and vitamin D deficiency co‐occurrence in geriatric memory patients
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PMCID: PMC10801816 PMID: 38259592
Abstract
INTRODUCTION
Vitamin B6 and D levels are not assessed routinely in geriatric memory patients. This study examined vitamin levels to determine the potential effects on cognition.
METHODS
A chart review was conducted of 203 consecutive patients over a 12‐month period. Levels of vitamins B1, B6, B12, and D were obtained on the day of clinic to identify deficiencies. A mental status exam (Mini Mental State Examination [MMSE]) was also performed.
RESULTS
One hundred sixty‐seven patients had one or more vitamin levels obtained on the day of clinical evaluation. Vitamin B6 deficiency was the most common (37.5%), followed by vitamin D deficiency (36.8%). A chi‐square test revealed significant co‐occurrence of deficiency of vitamins B6 and D (p < 0.001). Vitamin B6 and D deficiencies were associated with lower MMSE scores (p < 0.05).
DISCUSSION
Vitamin B6 and D deficiencies are common in geriatric patients. The coexistence of these vitamin deficiencies has a significant association with cognitive performance, indicating the clinical importance of monitoring and supplementation.
1. INTRODUCTION
Alzheimer's disease (AD) has been marked as a global epidemic, with age being the greatest risk factor for developing the neurodegenerative disease.
Vitamin B12 (cobalamin) is routinely checked in memory clinic patients and research subjects, but other central nervous system (CNS)–significant vitamins such as B6 (pyridoxine), B1 (thiamine), and D are not. Vitamin B6 and B12 deficiencies are associated with mild cognitive impairment and dementia.
Pyridoxine alone can enhance quantitative and qualitative memory through a variety of effects.
For example, pyridoxine is required for the synthesis of neurotransmitters, and as such is involved in both neuronal excitation and inhibition.
Vitamins B1 and D are not assessed routinely in memory patients even though they have been found to be associated with brain health and cognition. Thiamine (B1) deficiency is associated with cognitive deficits and encephalopathy, possibly due to reduced brain glucose metabolism.
Geriatric memory clinic patients are often deficient in vitamin D, and low levels of vitamin D have been reported to be correlated positively with cognitive test results.
The purpose of the present study is to determine the prevalence of deficiencies in vitamins B1, B6, B12, and D in geriatric memory patients and to explore the possibility of co‐occurring vitamin deficiencies and the relationship to baseline cognitive function.
2. METHODS
This retrospective cross‐sectional records review included a consecutive series of 203 new patients presenting to the UW Health Hospital and Clinics Memory Assessment Clinic between June 2019 and June 2020. Of these patients, 164 were assessed for levels of vitamins B1, B6, B12, and D (total 25‐(OH)D). Only test results obtained at the clinic on the day of the clinic visit were analyzed. Vitamin B1 was assessed from whole blood sample, whereas vitamins B6, B12, and D were tested from a serum sample. Vitamins B1 and B6 were assessed utilizing quantitative high‐performance liquid chromatography (HPLC)/liquid chromatography‐tandem mass spectrometry. Vitamin D was assessed via HPLC. Vitamin B12 was assessed using chemiluminescent immunoassay. No fasting or other special arrangements were made for testing. Deficiency thresholds were as follows: vitamin B1 <70,
and vitamin D (25‐(OH)D) <30 ng/mL.
All data and results were obtained from the patients’ medical records. The Mini Mental State Examination (MMSE) was administered on the date of the clinic visit in order establish a baseline cognitive function.
This study was reviewed by the University of Wisconsin Human Subjects Institutional Review Board (IRB) and was approved as meeting exempt status due to the de‐identified nature of the retrospective record review.
2.1. Statistical analyses
Along with descriptive statistics, t‐test of independent samples, chi‐square tests of independence, and risk estimates were conducted. Because vitamins B6 and D were the most frequent vitamin deficiencies in the sample, we further explored the relationship between vitamins B6 and D by including only those patients who had both vitamin levels evaluated (N = 96). To determine the relative risk of having a deficiency in vitamins B6 and D a Mantel‐Haenszel common odds ratio was calculated.
3. RESULTS
Records from 203 consecutive patients were reviewed; 164 patients had one or more vitamin levels obtained on the day of the clinic visit. Of the sample of 164 participants, 100 were female and 64 were male. The average age was 78 (mean = 77.51, SD = 7.55). The ethnicity of the population was predominantly White (157 (96%) white, 3 (1.8%) African American, 3 (1.8%) Asian, and 1 (0.6%) Hispanic). There were variable rates of vitamin levels tested across the patient sample. The mean and SD for the vitamin levels are as follows: vitamin B1 (mean = 122.33 nmol/L, SD = 36.86), vitamin B6 (mean = 73.34 nmol/L, SD = 84.59), vitamin B12 (mean = 650.16 pg/mL, SD = 439.52), and vitamin D (mean = 35.91 ng/mL, SD = 14.41). In Table 1, the number of patients who were evaluated for a given vitamin deficiency is indicated as well as the number and percent of patients who were found to have a vitamin deficiency. Vitamin B6 deficiency was the most common, found in 37.5% (48 of 128). The second most common deficiency was vitamin D at 36.8% (43 of 117). Finally, the mean MMSE score for the sample was 25.34 (SD = 4.49).
TABLE 1.
Vitamins tested in geriatric memory clinic patients.
Vitamin tested
Patients tested
Patients deficient
Percent deficient
B1
126
9
7.1%
B6
128
48
37.5%
B12
116
20
17.2%
D (25‐(OH)D)
117
43
36.8%
RESEARCH IN CONTEXT
Systematic review: The authors reviewed the literature using traditional (e.g., PubMed) sources and meeting abstracts and conference presentations. Although nutritional problems with folate and vitamin B12 deficiencies have been reported in memory patients, few reports of vitamin D, and no reports of vitamin B6 deficiency in memory patients were found. Furthermore, no significant co‐occurrence of vitamin B6 and D deficiencies has been reported in any clinic population, and the finding that both vitamin B6 and D deficiencies had a significant relationship to mental status screening scores is novel.
Interpretation: Our findings show that vitamin B6 and D deficiencies are common in the memory clinic patients and should be tested routinely , just as vitamin B12 is currently. The significant co‐occurrence indicates that if one is deficient, the other may also be deficient. The association with both vitamins B6 and D on cognitive performance indicates that testing for these vitamin deficiencies should be routine in all memory clinic patients.
Future directions: Our findings warrant the following efforts: (1) identify the incidence and prevalence of deficiencies in vitamins B6 and D in large memory patient samples; (2) examine the biochemical link in these disparate vitamins; (3) compare neurocognitive testing before and after treatment with vitamins B6 and D to clarify the connection between cognition and these vitamin deficiencies.
Of those participants with both vitamin B6 and D levels obtained, 27 of 96 (28.1%) had deficiencies in both vitamins B6 and D. In addition,, 12 (12.5%) had a vitamin B6 deficiency only and 14 (14.6%) had a vitamin D deficiency only. A Pearson chi‐square test of independence was calculated comparing the frequency of vitamin B6 deficiency with a co‐occurring vitamin D deficiency. A significant relationship was found between the two groups: (χ
2
(1, N = 96) = 18.884, p < 0.001). In addition, individuals had a 7 times higher relative risk for a deficiency in both vitamins (odds ratio [OR] = 6.911; 95% confidence interval [CI] = 2.785, 17.150; p < 0.001).
MMSE scores were examined based on vitamin B1, B6, B12, and D deficiencies. Among those with vitamin B1 and B12 deficiencies, there were no significant differences in the MMSE scores (see Figure 1). A significant difference was noted in MMSE scores for vitamin B6 only and vitamin D only, and this significant difference remained when the vitamin B6 and D deficiency groups were combined. Individuals that did not have a vitamin B6 and D deficiency had a mean MMSE score of 26 (SD = 4.29), whereas those with a deficiency in both vitamins B6 and D had a mean MMSE score of 23.04 (SD = 5.19), and this difference was significant, t(68) = 3.7, p = 0.01.
FIGURE 1.
Mini Mental State Examination (MMSE) MSE and vitamin deficiency.
4. DISCUSSION
In this geriatric population presenting for the initial memory clinic evaluation, patients were found to be most commonly deficient in two vitamins rarely assessed in memory patients, B6 and D. Vitamin B12 is assessed routinely in this population but was found to be deficient in only 17.2% of patients, less than half that of vitamins B6 and D.
Vitamin B6 is required for the synthesis of the neurotransmitters serotonin, norepinephrine, epinephrine, and γ‐aminobutyric acid(GABA), and as such is involved in both neuronal excitation and inhibition.
It has been reported previously that pyridoxine (vitamin B6) and pyridoxal phosphate deficiencies are associated with insomnia.
This is important because sleep is critical for normal cognition and prevention of AD.
The potential connection between vitamin B6 and cognition has been reported previously in kidney transplantation patients with mild cognitive impairment.
Although folate and vitamin B12 were rarely found to be deficient, vitamin B6 deficiency affected 44% of the patients with kidney transplants.
It has been reported that serum vitamin D levels are decreased significantly in patients with mild cognitive impairment and AD compared to healthy controls.
There is evidence that polymorphisms in the vitamin D receptor gene are associated with AD.
Vitamin D also modulates proinflammatory states and reduces the burden of amyloid beta (Aβ) plaque.
Calcitriol, an active vitamin D metabolite, has been shown to act in the blood mononuclear cells of patients with AD to promote Aβ plaque phagocytosis.
The positive association between vitamin B6 and D deficiencies is particularly intriguing, since they are from different nutritional sources. Furthermore, vitamin B6 is water soluble, whereas vitamin D is fat soluble. There is a higher risk (OR = 6.91) that vitamin B6 and D deficiencies will occur together warranting the recommendation that if one of these vitamins is found to be deficient, the other vitamin level should be evaluated.
Previous studies suggest that both vitamins B6 and D are important for cognition, a finding supported by this study. A deficiency of either vitamin B6 or D was found to be associated with significantly lower MMSE scores. A prior study of memory clinic patients in northern Wisconsin reported a significant positive correlation between vitamin D levels and MMSE scores.
This significant MMSE score difference is remarkable, and to our knowledge is unreported for any reversible factor affecting cognition.
A primary limitation of this cross‐sectional retrospective study design is that it does not allow for causal inferences or provide further insight into the association between vitamin levels and cognitive disturbances. In addition, patients were not fasted prior to vitamin level assessment because fasting would not be desirable to do prior to a cognitive assessment should hypoglycemia be produced. Lack of fasting could have impacted vitamin B6 levels, which is ideally tested after an 8 hour fast. Because we were looking for a deficiency rather than toxic vitamin B6 levels, this could have led to an underestimation of the prevalence of B6 deficiency, and, therefore, does not detract from the significance of our findings. Another limitation of the study is the lack of diversity within the population; 96% of the population reported their ethnicity as White.
Routine testing for vitamin B6 and D deficiencies could lead to repletion that would potentially improve cognitive performance and increase the likelihood of effective medical treatment. This is particularly relevant now, since the MMSE score is used to qualify patients with AD for treatment with the new disease‐modifying therapies, and patients with a vitamin B6 or D deficiency could fall below the allowable MMSE score for treatment in part due to this deficiency.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest. Author disclosures are available in the supporting information.
CONSENT STATEMENT
Consent was not necessary for this study, and IRB approval as an exempt study was documented.
Supporting information
Supporting Information
Click here for additional data file.
(384KB, pdf)
ACKNOWLEDGMENTS
Our gratitude to the UW Health Hospital and Clinics Memory Assessment Clinic staff for their support. We have the utmost appreciation for the patients included in this study. There was no funding associated with this project.
Przybelski AG, Bendlin BB, Jones JE, Vogt NM, Przybelski RJ. Vitamin B6 and vitamin D deficiency co‐occurrence in geriatric memory patients. Alzheimer's Dement. 2024;16:e12525. 10.1002/dad2.12525
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Associated Data
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Supplementary Materials
Supporting Information
Click here for additional data file.
(384KB, pdf)
Articles from Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring are provided here courtesy of Wiley
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