Studies In Man Therapies

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To date the only published studies that have evaluated the effects of different treatment modalities on cognition in type 1 diabetes, are the intensive insulin treatment trials

(48,95). In these trials cognition was monitored primarily in order to detect possible unwanted side effects of an increased incidence of hypoglycemic episodes. Neither study detected a deterioration of cognitive function in relation to the occurrence of hypo-glycemic episodes, but they also failed to show an improvement of cognition with improved glycemic control.

In type 2 diabetes some studies suggest that intensified glycemic control may improve cognition (96-99; but see ref. 100). However, the methodological quality of the studies is insufficient to draw firm conclusions (101). Alternative treatment modalities are also being considered. There is some evidence that treatment with the lipid-lowering drug atorvastatin has beneficial effects on learning in type 2 diabetes (102). Moreover, a recent randomized, double-blind, placebo-controlled crossover study showed that administration of the lip-hydroxysteroid dehydrogenase inhibitor carbenoxolone improved verbal memory after 6 weeks in 12 patients with type 2 diabetes (103). The rationale behind this treatment was that the compound might protect hippocampal cells from glucocorticoid-mediated damage that occurs in association with ageing (103).

Another interesting development, outside the field of diabetes, is the observation from a recent exploratory placebo-controlled trial in nondiabetic subjects with early AD that rosiglitazone, an insulin-sensitizing compound from the thiazolidinedione class, ameliorated cognitive decline (104). The effects of this compound on cognition were accompanied by an improvement of cerebrospinal fluid P-amyloid levels. Future studies should determine whether these compounds are superior than other classes of antihyperglycemic agents in preventing cognitive deterioration in patients with type 2 diabetes.

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