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Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study.
Clin Nutr. 2021 07; 40(7):4579-4584.CN

Abstract

BACKGROUND

Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia.

AIMS

To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults.

METHODS

This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models.

RESULTS

During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 μmol/L) but also those with low serum tHcy (≤8.9 μmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 μmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 μmol/L) were taking vitamin supplements.

CONCLUSIONS

Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.

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Authors+Show Affiliations

Bae JB
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea.
Han JW
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea.
Song J
Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Lee K
Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Kim TH
Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea.
Kwak KP
Department of Psychiatry, Dongguk University Gyeongju Hospital, Gyeongju, South Korea.
Kim BJ
Department of Psychiatry, Gyeongsang National University, School of Medicine, Jinju, South Korea.
Kim SG
Department of Neuropsychiatry, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.
Kim JL
Department of Psychiatry, School of Medicine, Chungnam National University, Daejeon, South Korea.
Moon SW
Department of Psychiatry, School of Medicine, Konkuk University and Konkuk University Chungju Hospital, Chungju, South Korea.
Park JH
Department of Neuropsychiatry, Jeju National University Hospital, Jeju, South Korea.
Ryu SH
Department of Psychiatry, School of Medicine, Konkuk University and Konkuk University Medical Center, Seoul, South Korea.
Youn JC
Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Yongin, South Korea.
Lee DY
Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
Lee DW
Department of Neuropsychiatry, Inje University Sanggye Paik Hospital, Seoul, South Korea.
Lee SB
Department of Psychiatry, Dankook University Hospital, Cheonan, South Korea.
Lee JJ
Department of Psychiatry, Dankook University Hospital, Cheonan, South Korea.
Jhoo JH
Department of Psychiatry, Kangwon National University, School of Medicine, Chuncheon, South Korea.
Kim KW
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea; Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, South Korea. Electronic address: kwkimmd@snu.ac.kr.

MeSH

AgedAlzheimer DiseaseDementiaDietary SupplementsFemaleHomocysteineHumansIndependent LivingMaleMiddle AgedProportional Hazards ModelsProspective Studies

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34229262

Citation

Bae, Jong Bin, et al. "Hypohomocysteinemia May Increases the Risk of Dementia and Alzheimer's Disease: a Nationwide Population-based Prospective Cohort Study." Clinical Nutrition (Edinburgh, Scotland), vol. 40, no. 7, 2021, pp. 4579-4584.
Bae JB, Han JW, Song J, et al. Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study. Clin Nutr. 2021;40(7):4579-4584.
Bae, J. B., Han, J. W., Song, J., Lee, K., Kim, T. H., Kwak, K. P., Kim, B. J., Kim, S. G., Kim, J. L., Moon, S. W., Park, J. H., Ryu, S. H., Youn, J. C., Lee, D. Y., Lee, D. W., Lee, S. B., Lee, J. J., Jhoo, J. H., & Kim, K. W. (2021). Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study. Clinical Nutrition (Edinburgh, Scotland), 40(7), 4579-4584. https://doi.org/10.1016/j.clnu.2021.05.034
Bae JB, et al. Hypohomocysteinemia May Increases the Risk of Dementia and Alzheimer's Disease: a Nationwide Population-based Prospective Cohort Study. Clin Nutr. 2021;40(7):4579-4584. PubMed PMID: 34229262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study. AU - Bae,Jong Bin, AU - Han,Ji Won, AU - Song,Junghan, AU - Lee,Kyunghoon, AU - Kim,Tae Hui, AU - Kwak,Kyung Phil, AU - Kim,Bong Jo, AU - Kim,Shin Gyeom, AU - Kim,Jeong Lan, AU - Moon,Seok Woo, AU - Park,Joon Hyuk, AU - Ryu,Seung-Ho, AU - Youn,Jong Chul, AU - Lee,Dong Young, AU - Lee,Dong Woo, AU - Lee,Seok Bum, AU - Lee,Jung Jae, AU - Jhoo,Jin Hyeong, AU - Kim,Ki Woong, Y1 - 2021/06/09/ PY - 2021/01/22/received PY - 2021/03/18/revised PY - 2021/05/31/accepted PY - 2021/7/7/pubmed PY - 2021/7/7/medline PY - 2021/7/6/entrez KW - Alzheimer disease KW - Dementia KW - Folic acid KW - Homocysteine KW - Vitamin SP - 4579 EP - 4584 JF - Clinical nutrition (Edinburgh, Scotland) JO - Clin Nutr VL - 40 IS - 7 N2 - BACKGROUND: Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. AIMS: To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. METHODS: This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. RESULTS: During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 μmol/L) but also those with low serum tHcy (≤8.9 μmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 μmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 μmol/L) were taking vitamin supplements. CONCLUSIONS: Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia. SN - 1532-1983 UR - https://www.unboundmedicine.com/medline/citation/34229262/Hypohomocysteinemia_may_increases_the_risk_of_dementia_and_Alzheimer's_disease:_A_nationwide_population_based_prospective_cohort_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0261-5614(21)00285-5 DB - PRIME DP - Unbound Medicine ER -