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.
Moderately elevated total serum homocysteine is associated with an increased risk of atherothrombotic vascular events. Accordingly, serum homocysteine is increased in patients with vascular dementia but is also increased in clinically diagnosed and histologically confirmed AD. It is generally considered that homocysteine potentiates endothelial and neuronal oxidative injury in these diseases. A complementary model of oxidative stress-induced hyperhomocystinemia is proposed by the authors. The hypothesis accounts for several unusual features relating to single-carbon metabolism and AD, including the absence of macrocytic anemia in these patients. It is suggested that cerebral oxidative stress augments the oxidation of an intermediate form of vitamin B(12) (cob[I]alamin) generated in the methionine synthase reaction, thereby impairing the metabolism of homocysteine. Oxidative stress also compromises the intraneuronal reduction of the vitamin to its metabolically active state. Currently available pharmaceutic forms of vitamin B(12) are unlikely to be utilized by neurons under these conditions. Glutathionylcobalamin might be preferential for the treatment of such patients.
Ten type 1 diabetic patients recorded their daily home blood glucose values, pre- and post-prandially, for 12 weeks. Blood was collected weekly for HbA1c and total haemoglobin measurement. A rolling 28-day mean of all blood glucose values and a glycation index (the ratio of the HbA1c to the rolling mean blood glucose) were calculated. In the pooled patients' data, there was a large scatter of results about the HbA1c versus mean blood glucose regression line. There was less variation in the results of individual patients. The glycation indices showed marked inter-individual variation, and in 60% of patients there was an inverse relationship between glycation index and mean blood glucose, suggesting a non-linear relationship between mean blood glucose and HbA1c. Patients should be monitored on the basis of their own previous results, and in some patients blood HbA1c may be a less sensitive index of mean blood glucose concentration at higher glucose levels.
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