Effect of Donepezil and Vitamin B12 Supplement on Serum Thyroid Profile in Alzheimer’s Disease

Main Article Content

Neelam Yeram
Shubhangi M. Dalvi
Vinayak W. Patil
Vinayak P. Kale
Kamlesh Jagiasi
Leela G. Abichandani


Aims: The aim of this study was to investigate thyroid status in Alzheimer’s Disease (AD) patients and its response to donepezil and vitamin B12 supplement therapy for 6 months.

Design: Case-Control Observational study.

Place and Duration: Department of Biochemistry, GGMC & Sir J. J. Group of Hospitals, Mumbai, India between March 2017 and July 2019.

Methodology: Case-Control study comprised of 71 AD patients and 70 healthy controls above 60 years of age.  Blood serum samples were analyzed for thyroid hormones levels by the chemiluminescence method. AD patients were treated with donepezil (5 mg/day) and vitamin B12 supplement (1.5 mg/day) and thyroid profile was observed at intervals of 3 and 6 months. Statistical evaluation was done by using IMB SPSS statistics version 25.

Results: Serum levels of thyroid hormones were low in euthyroid AD patients when compared with controls at the baseline level [T3 (120.64 ± 20.64 vs 127.8 ± 17.29), T4 (7.71 ± 2.34 vs 7.54 ± 1.85), FT3 (1.2 ± 0.13 vs 2.26 ± 0.63) and FT4 (0.79 ± 0.08 vs 1.29 ± 0.27)] except TSH which was increased in AD [TSH (2.71 ± 1.19 vs 2.34 ± 0.65)]. During follow-ups at 3 and 6 months, there was a slight decrease in TSH levels in response to the therapy.

Conclusion: The AD patients were euthyroid with low T3, FT3 and FT4 serum levels and high TSH serum levels. Thyroid hormones might play a role as markers for disease progression. Donepezil and vitamin B12 therapy could not benefit restore the normal thyroid functioning in a period of 6 months. Further longitudinal research with larger cohort might help in elucidating thyroid dysfunction in AD and develop novel therapeutic strategies.

Thyroid stimulating hormone, Alzheimer’s Disease, donepezil, vitamin B12.

Article Details

How to Cite
Yeram, N., M. Dalvi, S., Patil, V. W., Kale, V. P., Jagiasi, K., & Abichandani, L. G. (2020). Effect of Donepezil and Vitamin B12 Supplement on Serum Thyroid Profile in Alzheimer’s Disease. International Neuropsychiatric Disease Journal, 13(2), 1-8. https://doi.org/10.9734/indj/2019/v13i230108
Original Research Article


Chang YS, Wu YH, Wang CJ, Tang SH, Chen HL. The relationship between thyroid Status, cortisol level, cognition and neuropsychiatric symptoms in patients with alzheimer disease. Neuropsychiatry (London). 2018;08(03):786–93.

Tan ZS, Vasan RS. Thyroid function and Alzheimer’s disease. J Alzheimer’s Dis. 2009;16(3):503–7.

Chang YS, Wu YH, Wang CJ, Tang SH, Chen HL. Higher levels of thyroxine may predict a favorable response to donepezil treatment in patients with Alzheimer disease: A prospective, case-control study. BMC Neurosci. 2018;19(1):5–10.

Langlois MF, Lorrain D, Cunnane SC. Thyroid Function and Cognition during Aging. Curr Gerontol Geriatr Res. 2008;11.
(Article ID 474868).

Annerbo S, Lökk J. A Clinical Review of the Association of Thyroid Stimulating Hormone and Cognitive Impairment. ISRN Endocrinology; 2013.
Article ID 856017

Moon JH, Park YJ, Kim TH, Han JW, Choi SH, Lim S, et al. Lower-but-normal serum TSH level is associated with the development or progression of cognitive impairment in elderly: Korean longitudinal study on health and aging (KLOSHA). J Clin Endocrinol Metab. 2014;99(2):424– 32.

Pierre Tariot, Steven Salloway, Jane Yardley, Joan Mackell, Margaret Moline. Long-term safety and tolerability of donepezil 23 mg in patients with moderate to severe Alzheimer’s disease. BMC Research Notes. 2012;5:283.

Martin Farlow, Felix Veloso, Margaret Moline, Jane Yardley, Elimor Brand-Schieber, Francesco Bibbiani, et al. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer’s disease. BMC Neurology. 2011;11:57.

Fei Ma, Tianfeng Wu, Jiangang Zhao, Lu Ji, Aili Song, Meilin Zhang et al. Plasma Homocysteine and Serum Folate and Vitamin B12 Levels in Mild Cognitive Impairment and Alzheimer’s Disease: A Case-Control Study. Nutrients. 2017;9:725.
DOI: 10.3390/nu9070725

Fang-Fang Zheng, Shi-Hua Chen, Chuan-Yi Wen, Wei Guo, Han Xiao. Effects of donepezil combined with folic acid and vitamin B12 on serum levels of inflammatory factors, HCY, NSE and neurotransmitters in elderly patients with Alzheimer's disease complicated with hyperhomocysteinemia. Journal of Hainan Medical University. 2017;23(16):114- 117.

Hui Chen, Shuai Liu, Lu Ji, Tianfeng Wu, Yong Ji, Yuying Zhou, et al. Folic acid supplementation mitigates alzheimer’s disease by reducing inflammation: A randomized controlled trial. Mediators of Inflammation; 2016.
Article ID 5912146

Singh T, Sharma S, Nagesh S. SES status updated. Int J Res Med Sci. 2017;5(7): 3264–7.

B´egin ME, Langlois MF, Lorrain D, Cunnane SC. Thyroid function and cognition during aging. Current Geronto-logy and Geriatrics Research; 2008.
Article ID 474868

Annerbo S, Kivipelto M, Lökk J. A prospective study on the development of Alzheimer’ s disease with regard to thyroid-stimulating hormone and homo-cysteine. Dement Geriatr Cogn Disord. 2009; 28(3):275–80.

Forti P, Olivelli V, Rietti E, Maltoni B, Pirazzoli G, Gatti R, et al. Serum thyroid-stimulating hormone as a predictor of cognitive impairment in an elderly cohort. Gerontology. 2012;58(1):41–9.

Choi HJ, Byun MS, Yi D, Sohn BK, Lee JH, Lee JY, et al. Associations of thyroid hormone serum levels with in-vivo Alzheimer’s disease pathologies. Alzhei-mer’s Res Ther. 2017;9(1):1–9.

Tan ZS, Beiser A, Vasan RS, Auerbach S, Kiel DP, Wolf PA, et al. Thyroid function and the risk of Alzheimer’s disease: The framingham Study. Arch Intern Med. 2008;168(14):1514–20.

Karimi F, Haghighi AB, Petramfar P. Low levels of triiodothyronine in patients with Alzheimer’s disease. Iran J Med Sci. 2011;36(4):322–3.

Santos GAA, Pardi PC, Paulino N, Azevedo RG, Angel M, Paz C. Thyroid hormones and Alzheimer’s Disease. Alzheimer’s dement. 2016;12(7):P878–9. Available:http://dx.doi.org/10.1016/j.jalz.2016.06.1815

Kapaki E, Ilias I, Paraskevas GP. Thyroid function in patients with Alzheimer’s disease treated with cholinesterase inhibitors. Acta Neurobiol Exp (Wars). 2003;63:389–92.