Total serum homocysteine in senile dementia of Alzheimer type

The main hypothesis was that subtle vitamin B12 deficiencies occur more commonly in senile dementia of Alzheimer type (SDAT) that in healthy elderly individuals, and may be revealed by elevated total serum homocysteine (tHcy). A subsidiary hypothesis was that such deficiencies would be nutritionally independent as determined by retinol binding protein (RBP).

A prospective case-controlled survey.

A Welsh urban psychogeriatric assessment centre and local general practice.

Thirty patients, aged 65 or over, seen consecutively in 1994 with features compatible with DSM-III-R criteria for primary degenerative dementia of Alzheimer type and 30 cognitively intact age-matched control subjects.

Diagnosis was assessed using the CAMDEX. Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE scores for control subjects. THcy was measured using high performance liquid chromatography (HPLC), and RBP assayed by a radial immunodiffusion method.

Patients had a highly significant elevation of tHcy compared with control (p < 0.0001). Multiple regression highlighted the interrelated effects of tHcy and total serum cobalamin on cognitive scores. RBP did not differ between groups. Macrocytosis was absent, and neutrophil hypersegmentation uncommon, in hyperhomocysteinaemic patients.

SDAT patients have significantly elevated tHcy. This is independent of RBP determined nutritional status. 'Classical' haematological changes of cobalamin or folate deficiency are poor predictors of tHcy in these patients. Aberrant cobalamin tissue delivery appears to contribute to SDAT cognitive decline. Relative contributions of other tHcy determinants require further investigation.