Methods for treating mild cognitive impairment using a glucocorticoid-specific receptor antagonist

Abstract

This invention generally pertains to the field of psychiatry. In particular, this invention pertains to the discovery that agents which inhibit the binding of cortisol to its receptors can be used in methods for treating mild cognitive impairment. Mifepristone, a potent specific glucocorticoid receptor antagonist, can be used in these methods. The invention also provides a kit for treating mild cognitive impairment in a human including a glucocorticoid receptor antagonist and instructional material teaching the indications, dosage and schedule of administration of the glucocorticoid receptor antagonist.

What is claimed is:  
     
         1 . A method of treating a patient with mild cognitive impairment who is 45 years or older and has normal levels of cortisol for a human population of that age, the method comprising administering to the patient a therapeutically effective amount of a specific glucocorticoid receptor antagonist, wherein the patient meets the following criteria: 
 (i) obtains at least one perfect score on the Folstein Mini Mental Status Exam in three administrations of said Exam;    (ii) receives a rating of 0.5 on the Clinical Dementia Rating Scale, and    (iii) scores 1.5 standard deviations or below the age- and education-adjusted normal value on a paragraph recall test.    
     
     
         2 . The method of  claim 1 , wherein the amount of glucocorticoid receptor antagonist will prevent further memory impairment.  
     
     
         3 . The method of  claim 1 , wherein the amount of glucocorticoid receptor antagonist will improve performance on a paragraph recall test.  
     
     
         4 . The method of  claim 1 , wherein the glucocorticoid receptor antagonist comprises a steroidal skeleton with at least one phenyl-containing moiety in the 11-beta position of the steroidal skeleton.  
     
     
         5 . The method of  claim 4 , wherein the phenyl-containing moiety in the 11-beta position of the steroidal skeleton is a dimethylaminophenyl moiety.  
     
     
         6 . The method of  claim 4 , wherein the glucocorticoid receptor antagonist comprises mifepristone.  
     
     
         7 . The method of  claim 4 , wherein the glucocorticoid receptor antagonist is selected from the group consisting of RU009 and RU044.  
     
     
         8 . The method of  claim 1 , wherein the glucocorticoid receptor antagonist is administered in a daily amount of between about 0.5 to about 20 mg per kilogram of body weight per day.  
     
     
         9 . The method of  claim 8 , wherein the glucocorticoid receptor antagonist is administered in a daily amount of between about 1 to about 10 mg per kilogram of body weight per day.  
     
     
         10 . The method of  claim 9 , wherein the glucocorticoid receptor antagonist is administered in a daily amount of between about 1 to about 4 mg per kilogram of body weight per day.  
     
     
         11 . The method of  claim 1 , wherein the administration is once per day.  
     
     
         12 . The method of  claim 1 , wherein the mode of administration is oral.  
     
     
         13 . The method of  claim 1 , wherein the mode of administration is by a transdermal application, by a nebulized suspension, or by an aerosol spray.  
     
     
         14 . A kit for treating MCI in a human, the kit comprising: 
 a specific glucocorticoid receptor antagonist; and,    an instructional material teaching the indications, dosage and schedule of administration of the glucocorticoid receptor antagonist to a patient with mild cognitive impairment who is 45 years or older and has normal levels of cortisol for that age, wherein the patient: 
 (i) obtains at least one perfect score on the Folstein Mini Mental Status Exam in three administrations of said Exam;  
 (ii) receives a rating of 0.5 on the Clinical Dementia Rating Scale, and  
 (iii) scores 1.5 or more standard deviations below the age- and education-adjusted normal value on a paragraph recall test.  
   
     
     
         15 . The kit of  claim 14 , wherein the instructional material indicates that the glucocorticoid receptor antagonist can be administered in a daily amount of about 0.5 to about 20 mg per kilogram of body weight per day.  
     
     
         16 . The kit of  claim 14 , wherein the instructional material indicates that the glucocorticoid receptor antagonist can be administered in a daily amount of about 1 to about 10 mg per kilogram of body weight per day.  
     
     
         17 . The kit of  claim 14 , wherein the instructional material indicates that the glucocorticoid receptor antagonist can be administered in a daily amount of about 1 to about 4 mg per kilogram of body weight per day.  
     
     
         18 . The kit of  claim 14 , wherein the glucocorticoid receptor antagonist is mifepristone.  
     
     
         19 . The kit of  claim 14 , wherein the mifepristone is in tablet form.