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Homocysteine as a predictor of cognitive decline in Alzheimers disease
International Journal of Geriatric Psychiatry, 06/02/09

Oulhaj A et al. - 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.

Methods

This study 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.

Exclusive Author Commentary
A. David Smith, 06/03/09

The findings have two main clinical implications: first, a high baseline homocysteine level can be used to predict that a patient is likely to decline more rapidly; second, since homocysteine levels can be lowered by B vitamin treatment, trials should be initiated on Alzheimer patients who are aged less than 75 to see if lowering homocysteine can slow disease progression. Whether or not high homocysteine is causal, it is certainly a good prognostic marker.