Research Article

Homocysteine as a predictor of cognitive decline in Alzheimer's disease

  1. Abderrahim Oulhaj1,
  2. Helga Refsum1,2,
  3. Helen Beaumont1,
  4. Jonathan Williams1,
  5. Elizabeth King1,
  6. Robin Jacoby3,
  7. A. David Smith1,*

Article first published online: 29 MAY 2009

DOI: 10.1002/gps.2303

Issue

International Journal of Geriatric Psychiatry

International Journal of Geriatric Psychiatry

Volume 25, Issue 1, pages 82–90, January 2010

Additional Information

How to Cite

Oulhaj, A., Refsum, H., Beaumont, H., Williams, J., King, E., Jacoby, R. and Smith, A. D. (2010), Homocysteine as a predictor of cognitive decline in Alzheimer's disease. International Journal of Geriatric Psychiatry, 25: 82–90. doi: 10.1002/gps.2303

Author Information

  1. 1

    Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK

  2. 2

    Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, Norway

  3. 3

    University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX

*Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Publication History

  1. Issue published online: 15 DEC 2009
  2. Article first published online: 29 MAY 2009
  3. Manuscript Accepted: 26 MAR 2009
  4. Manuscript Received: 13 FEB 2009

Funded by

  • Alzheimer's Research Trust
  • Charles Wolfson Charitable Trust
  • Health Foundation
  • Norman Collisson Foundation
  • John Coates Charitable Trust
  • Southern Trust
  • CHK Charity
  • Bristol–Myers Squibb
  • Merck & Co Inc.

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Keywords:

  • homocysteine;
  • Alzheimer's disease;
  • cognitive decline;
  • non-linear model

Abstract

Objective

Moderately elevated levels of plasma total homocysteine are associated with an increased risk of developing Alzheimer's disease. We have tested whether baseline concentrations of homocysteine relate to the subsequent rate of cognitive decline in patients with established Alzheimer's disease (AD).

Methods

In 97 patients with AD, 73 pathologically-confirmed, we analysed the decline of global cognitive test scores (CAMCOG) over time from the first assessment for at least three 6-monthly visits up to a maximum of 9.5 years (in total 689 assessments). Non-linear mixed-effects statistical models were used.

Results

Baseline homocysteine levels showed a concentration-response relationship with the subsequent rate of decline in CAMCOG scores: the higher the homocysteine, the faster the decline. The relationship was significant in patients aged < 75 years who had not suffered a prior stroke. For example, in patients aged 65 years with a baseline homocysteine of 14 µmol/L, the decline from a CAMCOG score of 88 to a score of 44 occurred 19.2 (95% CI 6.8, 31.6) months earlier than in patients with a baseline homocysteine of 10 µmol/L.

Conclusions

Raised homocysteine concentrations within the normal range among the elderly strongly relate to the rate of global cognitive decline in patients with Alzheimer disease. Plasma homocysteine can readily be lowered by B-vitamin treatment and trials should be carried out to see if such treatments can slow the rate of cognitive decline in relatively young patients with Alzheimer disease. Copyright © 2009 John Wiley & Sons, Ltd.

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