Methods and compositions for improved cognition

1. A method for improving cognitive function or inhibiting cognitive decline in an individual in need thereof, comprising administering to the individual an effective amount of a polypeptide that includes an amino acid sequence that is at least 95% identical to the sequence of the KL1 domain contained in SEQ. ID NO:1, with the proviso that the polypeptide is not a fusion protein that also contains a fibroblast growth factor (FGF),

wherein the administering is systemic or peripheral, thereby improving cognitive function or inhibiting cognitive decline in the individual.

2. A method for improving cognitive function or inhibiting cognitive decline in an individual in need thereof, comprising administering to the individual an effective amount of a polypeptide that comprises a klotho KL1 domain, wherein the KL1 domain includes the beta-glucosidase/6-phospho-beta-glucosidase/beta-galactosidase motif that resides between amino acids 62-497 of SEQ. ID NO:1, with the proviso that the polypeptide is not a fusion protein that also contains a fibroblast growth factor (FGF),

wherein the administering is systemic or peripheral, thereby improving cognitive function or inhibiting cognitive decline in the individual.

3. A method for improving cognitive function or inhibiting cognitive decline in an individual in need thereof, comprising administering to the individual an effective amount of a polypeptide that comprises a klotho KL1 domain, wherein the KL1 domain has at least one and up to 5% altered, inserted or deleted amino acids compared with the amino acid sequence of the KL1 domain in SEQ. ID NO:1, with the proviso that the polypeptide is not a fusion protein that also contains a fibroblast growth factor (FGF),

wherein the administering is systemic or peripheral, thereby improving cognitive function or inhibiting cognitive decline in the individual.

4. The method of claim 1 , wherein the polypeptide further includes an amino acid sequence that is at least 95% identical to the sequence of the KL2 domain contained in SEQ. ID NO:1.

5. The method of claim 1 , further comprising testing the cognitive function of the individual after administering the polypeptide.

6. The method of claim 1 , which improves motor function in the individual.

7. The method of claim 1 , wherein the polypeptide comprises an extracellular portion of human klotho formed by enzymatic cleavage between the KL1 and KL2 domains.

8. The method of claim 7 , wherein the polypeptide ends in the amino acid sequence shown in SEQ. ID NO:2.

9. The method of claim 1 , wherein the polypeptide comprises a soluble splice variant of klotho.

10. The method of claim 9 , wherein the polypeptide comprises the KL1 domain but not the KL2 domain of human klotho.

11. The method of claim 10 , wherein the polypeptide ends in the amino acid sequence shown in SEQ. ID NO:3.

12. The method of claim 1 , wherein the polypeptide is a fusion protein that also includes a sequence of up to 100 additional amino acids.

13. The method of claim 1 , wherein the polypeptide has beta-glucuronidase activity.

14. The method of claim 1 , wherein the polypeptide binds or promotes activity of FGF23.

15. The method of claim 1 , wherein the polypeptide results in induction of c-fos or increased expression of GluN2B.

16. The method of claim 1 , wherein the polypeptide suppresses wnt signaling, insulin signaling, or transforming growth factor beta-1 (TGF-β1) activity.

17. The method of claim 1 , wherein the polypeptide is administered intravenously or subcutaneously.

18. The method of claim 1 , wherein the individual has traumatic brain injury.

19. The method of claim 1 , wherein the individual has schizophrenia.

20. The method of claim 1 , wherein the individual has Alzheimer's disease, frontotemporal dementia, Lewy body dementia, or cognitive impairment consequent to stroke.

21. The method of claim 1 , wherein the individual has Parkinson's disease.