Treatment of cognitive disorders
View Patent ↗The invention relates to treatments of cognitive disorders e.g. Mild Cognitive Disorder comprising the use of agents which are capable of lowering homocysteine levels in a subject, preferably a human subject. Aspects of the invention relate to a method of treating such disorders comprising administering one or more B vitamins e.g. folic acid, Vitamin B 6 and/or Vitamin B 12 or derivatives thereof.
1. A method for treating mild cognitive impairment (MCI) in a subject, the method comprising administering to the subject a therapeutically effective amount of folic acid, vitamin B 6 and vitamin B 12 , wherein:
the folic acid is administered in a daily amount of approximately 0.1 mg to approximately 1.5 mg;
the vitamin B 6 is administered in a daily amount of approximately 1 mg to approximately 30 mg; and
the vitamin B 12 is administered in a daily amount of approximately 0.01 mg to approximately 1.0 mg,
wherein the method provides a reduction in brain atrophy by a factor of at least 2 per year compared to the absence of administration of the folic acid, vitamin B 6 and vitamin B 12 .
2. A method for retarding the onset and/or development of MCI in a subject, the method comprising administering to the subject a therapeutically effective amount of folic acid, vitamin B 6 and vitamin B 12 , wherein:
the folic acid is administered in a daily amount of approximately 0.1 mg to 6 approximately 1.5 mg;
the vitamin B 6 is administered in a daily amount of approximately 1 mg to approximately 30 mg; and
the vitamin B 12 is administered in a daily amount of approximately 0.01 mg to approximately 1.0 mg,
wherein the method provides a reduction in brain atrophy by a factor of at least 2 per year compared to the absence of administration of the folic acid, vitamin B 6 and vitamin B 12 .
3. A method for improving cognitive function in a subject with MCI, the method comprising administering to the subject a therapeutically effective amount of folic acid, vitamin B 6 and vitamin B 12 , wherein:
the folic acid is administered in a daily amount of approximately 0.1 mg to approximately 1.5 mg;
the vitamin B 6 is administered in a daily amount of approximately 1 mg to approximately 30 mg; and
the vitamin B 12 is administered in a daily amount of approximately 0.01 mg to approximately 1.0 mg,
wherein the method provides a reduction in brain atrophy by a factor of at least 2 per year compared to the absence of administration of the folic acid, vitamin B 6 and vitamin B 12.
4. The method of claim 1 , wherein the subject is at least 60 years old.
5. The method of claim 4 , wherein the subject is at least 70 years old.
6. The method of claim 2 , wherein the subject is at least 50 years old.
7. The method of claim 3 , wherein the subject is at least 50 years old.
8. The method of claim 1 , wherein the subject is at least 50 years old.
9. The method of claim 1 , which comprises administering a composition comprising the folic acid, the vitamin B 6 and the vitamin B 12 .
10. The method of claim 2 , which comprises administering a composition comprising the folic acid, the vitamin B 6 and the vitamin B 12 .
11. The method of claim 3 , which comprises administering a composition comprising the folic acid, the vitamin B 6 and the vitamin B 12 .
12. The method of claim 1 , wherein: the folic acid is administered in an amount of from approximately 0.5 mg to approximately 1.5 mg.
13. The method of claim 2 , wherein: the vitamin B 6 is administered in an amount of approximately 15 mg to approximately 30 mg.
14. The method of claim 3 , wherein: the vitamin B 12 is administered in an amount of approximately 4.0 mg to approximately 1.0 mg.
15. The method of claim 9 , wherein:
the folic acid is in an amount of approximately 0.5 mg to approximately 1.5 mg;
the vitamin B 6 is in an amount of approximately 15 mg to approximately 30 mg;
the vitamin B 12 is in an amount of approximately 0.4 mg to approximately 1.0 mg.
16. The method of claim 10 :
the folic acid is in an amount of approximately 0.5 mg to approximately 1.5 mg;
the vitamin B 6 is in an amount of approximately 15 mg to approximately 30 mg;
the vitamin B 12 is in an amount of approximately 0.4 mg to approximately 1.0 mg.
17. The method of claim 11 , wherein the folic acid is in an amount of approximately 0.5 mg to approximately 1.5 mg;
the vitamin B 6 is in an amount of approximately 15 mg to approximately 30 mg;
the vitamin B 12 is in an amount of approximately 0.4 mg to approximately 1.0 mg.
18. The method of claim 1 , wherein:
attention is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
executive function is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
learning or memory is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 .
19. The method of claim 2 , wherein:
attention is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
executive function is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
learning or memory is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 .
20. The method of claim 3 , wherein:
attention is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
executive function is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
learning or memory is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 memory is improved in the subject following administration of the at least one agent.
21. The method of claim 1 , wherein the subject has a baseline tHcy exceeding approximately 9.5 μmol/L.
22. The method of claim 1 , wherein the vitamin B 12 is as cyanocobalamin, methylcobalamin, hydroxocobalamin or adenosylcobalamin or a salt thereof; and/or wherein the folic acid is as 5-methyltetrahydrofolate, 5,10-methylenetetrahydrofolate, 5,10-methenyltetrahydrofolate, 5,10-formiminotetrahydrofolate, 5-formyltetrahydrofolate (leucovorin) or 10-formyltetrahydrofolate or a salt thereof or is as a salt of folic acid; and/or wherein the vitamin B 6 is as pyridoxine or a salt thereof.
23. A method which comprises administering to a subject a therapeutically effective amount of at least one agent which reduces brain atrophy, the method being selected from:
(i) a method for treating mild cognitive impairment (MCI) in the subject;
(ii) a method for retarding the onset and/or development of MCI in the subject;
(iii) a method for improving cognitive function in the subject, wherein the subject has MCI,
wherein the method comprises administering a dosage form which comprises approximately 0.1 mg to approximately 1.5 mg of folic acid, approximately 1 mg to approximately 30 mg vitamin B 6 and approximately 0.01 mg to approximately 1.0 mg of vitamin B 12 , and wherein the method provides a reduction in brain atrophy by a factor of at least 2 per year compared to the absence of administration of the folic acid, vitamin B 6 and vitamin B 12 .
24. The method of claim 23 , wherein the subject's level of baseline tHcy exceeds 9.5 μmol/L.
25. The method of claim 23 wherein the vitamin B 12 is as cyanocobalamin, methylcobalamin, hydroxocobalamin or adenosylcobalamin or a salt thereof, and/or wherein the folic acid is as 5-methyltetrahydrofolate, 5,10-methylenetetrahydrofolate, 5,10-methenyltetrahydrofolate, 5,10-formiminotetrahydrofolate, 5-formyltetrahydrofolate (leucovorin) or 10-formyltetrahydrofolate or a salt thereof.
26. The method of claim 1 , wherein the subject is at least 50 years old.
27. The method of claim 1 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months.
28. The method of claim 2 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months.
29. The method of claim 3 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months.
30. The method of claim 2 wherein the subject has a baseline tHcy exceeding above about 9.5 μmol/L.
31. The method of claim 3 wherein the subject has a baseline tHcy exceeding above about 9.5 μmol/L.
32. A method for retarding the onset and/or development of MCI in a subject or for improving cognitive function in a subject with MCI, the method comprising administering to the subject for a minimum of 18 months a therapeutically effective amount of folic acid, vitamin B 6 and vitamin B 12 , wherein:
the folic acid is in an amount of approximately 0.5 mg to approximately 1.5 mg;
the vitamin B 6 is in an amount of approximately 15 mg to approximately 30 mg; and
the vitamin B 12 is in an amount of approximately 0.4 mg to approximately 1.0 mg,
wherein the method provides a reduction in brain atrophy by a factor of at least 2 per year compared to the absence of administration of the folic acid, vitamin B 6 and vitamin B 12 .
33. The method of claim 32 , wherein the folic acid, vitamin B 6 and vitamin B 12 are administered at least once a day for the minimum period of at least 18 months.
34. The method of claim 32 , wherein the folic acid, vitamin B 6 and vitamin B 12 are administered at least once a day for a minimum period of at least 24 months.
35. The method of claim 32 , wherein the vitamin B 12 is as cyanocobalamin, methylcobalamin, hydroxocobalamin or adenosylcobalamin or a salt thereof; and/or wherein the folic acid is as 5-methyltetrahydrofolate, 5,10-methylenetetrahydrofolate, 5,10-methenyltetrahydrofolate, 5,10-formiminotetrahydrofolate, 5-formyltetrahydrofolate (leucovorin) or 10-formyltetrahydrofolate or a salt thereof or is as a salt of folic acid; and/or wherein the vitamin B 6 is as pyridoxine or a salt thereof.
36. The method of claim 32 , wherein:
attention is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
executive function is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 ; and/or
learning or memory is improved in the subject following administration of the folic acid, vitamin B 6 and vitamin B 12 .
37. The method of claim 33 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months and has a baseline tHey exceeding about 13 μmol/L.
38. The method of claim 1 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months and has a baseline tHcy exceeding about 13 μmol/L.
39. The method of claim 2 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months and has a baseline tHcy exceeding about 13 μmol/L.
40. The method of claim 3 wherein the subject is administered the folic acid, vitamin B 6 and vitamin B 12 for a minimum of 18 months and has a baseline tHey exceeding about 13 μmol/L.
41. The method of claim 1 , wherein the folic acid is administered in a daily amount of approximately 0.8 mg, the vitamin B 6 is administered in a daily amount of approximately 20 mg and the vitamin B 12 is administered in a daily amount of approximately 0.5 mg.
42. A method of reducing brain atrophy, wherein the method consists essentially of administering to a subject a therapeutically effective amount of the following:
(a) folic acid in an amount of approximately 0.1 mg to approximately 1.5 mg;
(b) vitamin B 6 in an amount of approximately 1 mg to approximately 30 mg; and
(c) vitamin B 12 in an amount of approximately 0.01 mg to approximately 1.0 mg, wherein the method provides a reduction in brain atrophy by a factor of at least 2 compared to the absence of administration of the folic acid, vitamin B 6 and vitamin B 12 .