Homocysteine and Cognitive Decline in Healthy Elderly

Homocysteine and Cognitive Decline in Healthy Elderly

McCaddon A.a · Hudson P.b · Davies G.b · Hughes A.c · Williams J.H.H.d · Wilkinson C.a

aUniversity of Wales College of Medicine, Wrexham, bBiochemistry Department, Wrexham Maelor Hospital, Wrexham, cRoyal Alexandra Hospital, Paisley, dBiology Department, Chester College, Chester, UK


Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer’s disease (AD), vascular dementia and ‘age-associated memory impairment’. Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period. Homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance independently of age, sex, education, renal function, vitamin B status, smoking and hypertension (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills.

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