A trial of thiamine in Alzheimer's disease. Thiamine and Alzheimer's disease. A pilot study. Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
Because a previous short-term study demonstrated a statistically significant, but not clinically important, improvement in cognitive test scores during thiamine treatment in patients with dementia of the Alzheimer's type, a 12-month, double-blind, parallel-group study was conducted to examine whether long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type. Fifteen subjects were enrolled and 10 completed the 1-year study. Data are available for two additional subjects through the first 9 months of study. No significant differences were found between the placebo and thiamine groups at any point during the study. In both groups, overall means for the Mini-Mental State Examination, verbal learning, and naming scores decreased significantly over the 12-month study period. These results do not support the hypothesis that long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type. As a test of the significance of previously described biochemical abnormalities in thiamine-dependent enzymes in brains and other tissues in patients with Alzheimer's disease, a double-blind, placebo-controlled, crossover, outpatient pilot study compared the effects of 3 g/d of oral thiamine hydrochloride for three months with those of a niacinamide placebo. Eleven moderately impaired patients with "probable Alzheimer's disease" by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria completed the study. All patients were well nourished and had no stigmata of dietary thiamine deficiency. Their initial mean +/- SEM Mini-Mental State Examination score was 14.2 +/- 1.4, and the mean age was 72 years. Global cognitive rating by the Mini-Mental State Examination was higher during three months with 3 g/d of oral thiamine hydrochloride than with niacinamide placebo. Behavioral ratings, however, did not differ significantly, nor did clinical state when it was judged subjectively. Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.
It is not possible to draw any conclusions from this review. The number of people included in the studies is less than 50 and the reported results are inadequate.