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Serum homocysteine and risk of dementia in Japan.
J Neurol Neurosurg Psychiatry. 2020 05; 91(5):540-546.JN

Abstract

OBJECTIVE

To examine the association between serum total homocysteine levels (tHcy) and dementia risk.

METHODS

A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia.

RESULTS

During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07).

CONCLUSION

High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.

Authors+Show Affiliations

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan nino@eph.med.kyushu-u.ac.jp. Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Pub Type(s)

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

Language

eng

PubMed ID

32234968

Citation

Chen, Sanmei, et al. "Serum Homocysteine and Risk of Dementia in Japan." Journal of Neurology, Neurosurgery, and Psychiatry, vol. 91, no. 5, 2020, pp. 540-546.
Chen S, Honda T, Ohara T, et al. Serum homocysteine and risk of dementia in Japan. J Neurol Neurosurg Psychiatry. 2020;91(5):540-546.
Chen, S., Honda, T., Ohara, T., Hata, J., Hirakawa, Y., Yoshida, D., Shibata, M., Sakata, S., Oishi, E., Furuta, Y., Kitazono, T., & Ninomiya, T. (2020). Serum homocysteine and risk of dementia in Japan. Journal of Neurology, Neurosurgery, and Psychiatry, 91(5), 540-546. https://doi.org/10.1136/jnnp-2019-322366
Chen S, et al. Serum Homocysteine and Risk of Dementia in Japan. J Neurol Neurosurg Psychiatry. 2020;91(5):540-546. PubMed PMID: 32234968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum homocysteine and risk of dementia in Japan. AU - Chen,Sanmei, AU - Honda,Takanori, AU - Ohara,Tomoyuki, AU - Hata,Jun, AU - Hirakawa,Yoichiro, AU - Yoshida,Daigo, AU - Shibata,Mao, AU - Sakata,Satoko, AU - Oishi,Emi, AU - Furuta,Yoshihiko, AU - Kitazono,Takanari, AU - Ninomiya,Toshiharu, Y1 - 2020/03/31/ PY - 2019/11/01/received PY - 2020/03/06/revised PY - 2020/03/23/accepted PY - 2020/4/3/pubmed PY - 2020/11/13/medline PY - 2020/4/3/entrez SP - 540 EP - 546 JF - Journal of neurology, neurosurgery, and psychiatry JO - J Neurol Neurosurg Psychiatry VL - 91 IS - 5 N2 - OBJECTIVE: To examine the association between serum total homocysteine levels (tHcy) and dementia risk. METHODS: A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia. RESULTS: During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07). CONCLUSION: High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy. SN - 1468-330X UR - https://www.unboundmedicine.com/medline/citation/32234968/Serum_homocysteine_and_risk_of_dementia_in_Japan_ L2 - https://jnnp.bmj.com/lookup/pmidlookup?view=long&pmid=32234968 DB - PRIME DP - Unbound Medicine ER -