Analyzer. Jan-Håkan Jansson became MD 1979, specialist in cardiology 1988 and in internal medicine 1989. His dissertation 1990 for the PhD grade was on thromboembolism and fibrinolysis. He serves as consultant in Skellefteå . His scientific activity was acknowledged by promotion to associate professor at the Umeå University 1997. He now reviews a recent report on homocysteine and dementia (1).

General background. Deficiency of vitamin B12 and folate is related to hyperhomocysteinemia and may be associated with neuropsychiatric symptoms. Cardiovascular risk factors are related to dementia of both vascular type and Alzheimer type. Elevated total homocysteine has been associated with cardiovascular morbidity and mortality in some studies but not in others.

Previous studies on dementia. An inverse relation between homocysteine and cognitive function has been reported and in two case-control studies subjects with Alzheimer disease had elevated homocysteine concentrations. However, dementia may influence vitamin intake and thus be the reason to and not the reason of hyperhomocysteinemia. In a prospective study, homocyesteine was not related to cognitive decline during follow-up.

Present study. In the present Framingham study (1), plasma levels of homocysteine were analyzed along with concentrations of folate, vitamin B12 and B6 in 1092 subjects (42% of the original population), who had been screened 1986 through 1990 and eight years earlier without signs of dementia at these occasions. Over 60% of this population were women and the mean age was 76 years. During the eight-year-long follow-up 111 subjects developed dementia and 83 of these were classified as Alzheimer disease.

There was a significant association between total homocysteine levels and the risk of dementia of any type, Alzheimer disease included. This relation was independent to age, sex, apolipoprotein E genotype, folate, vitamin B6 and B12, creatinine and cardiovascular risk factors (smoking status, cholesterol, blood pressure, diabetes mellitus, body mass index).

Hyperhomocysteinemia (plasma homocysteine >14 micromoles per liter) was associated with a 1.9 relative risk of dementia (95% confidence interval 1.3 to 2.8).The relation between homocysteine levels and dementia was similar for samples taken at both screening occasions. Thus, the elevation of homocysteine precedes the manifestation of the disease.

After adjustment for age, sex, and apolipoprotein E genotype, there was no relation between the concentration of folate, vitamin B6 or B12 and the risk of developing dementia of any type, Alzheimer disease included.

Summary. The authors summarize (1), that their results must be evaluated in other cohort studies. Proof of a causal association between homocysteine and development of dementia will require controlled clinical trials showing that decreasing plasma homocysteine will reduce the risk of dementia.

Jan-Håkan Jansson
janhakan.jansson.ss@vll.se
Department of Internal Medicine
Skellefteå Hospital
SE-931 86 Skellefteå, Sweden

1. Seshadri S, Beiser A, Selhub J, Jaques PF, Rosenberg IH, D´Agostino RB, Wilson PWF, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer´s disease. N Engl J Med 2002;346:476-483

Published November 5, 2002