Personalized Medicine Approach for Treating Cognitive Loss

Abstract

The present invention includes methods for selecting a therapy for improved cognition as well as prevention of cognitive loss/dysfunction using one or more endophenotypes comprising: obtaining a sample from a subject; measuring biomarkers that differentiate between an inflammatory, a metabolic, a neurotrophic, and a depressive endophenotype; and selecting a course of treatment for the subject based on whether the subject is scored as having a high or a low endophenotype for one or more of the inflammatory, a metabolic, a neurotrophic, and a depressive endophenotypes.

What is claimed is: 
     
         1 . A method for selecting a treatment for improved cognition or prevention of cognitive dysfunction/loss using one or more antidepressant therapies comprising:
 determining a depressive endophenotype (DepE) score from a subject; and   if the subject has an increase in the DepE score that is indicative of a depressive endophenotype, selecting a course of treatment for the subject, wherein the treatment is selected from at least one of: an antidepressant, a selective serotonin reuptake inhibitor, a selective serotonin 2C (5-HT2C) antagonist, a serotonin-norepinephrine reuptake inhibitor, or a tricyclic antidepressant.   
     
     
         2 . The method of  claim 1 , further comprising the step of:
 generating a DepE score by determining an increase in one or more of the following: feeling of worse memory problems, feeling downhearted and blue, feeling worthless, frequently feel like crying, and trouble concentrating.   
     
     
         3 . The method of  claim 1 , wherein elevation of DepE score identifies those eligible for antidepressant therapy for improved cognition or prevention of cognitive loss. 
     
     
         4 . The method of  claim 1 , wherein the cognitive dysfunction is a disease or condition selected from Alzheimer's Disease, Parkinson's Disease, Down's syndrome, Frontotemporal dementia, Dementia with Lewy Bodies, Multiple sclerosis, traumatic brain injury, depression, schizophrenia, bipolar disease (and other mental illness), diabetes, hypertension, stroke, heart attack, dyslipidemia, other conditions/diseases or aging. 
     
     
         5 . The method of  claim 1 , wherein the DepE score is analyzed with a receiver operating characteristic (ROC) curve analysis, and an increase in the DepE score is indicative of Alzheimer's Disease. 
     
     
         6 . The method of  claim 1 , wherein a decrease in the DepE score after treatment is indicative of an improvement in at least one of: immediate memory scores and delayed memory scores. 
     
     
         7 . The method of  claim 1 , wherein the treatment is initiated before the subject is diagnosed with Alzheimer's Disease. 
     
     
         8 . The method of  claim 1 , wherein the subject has at least a one standard deviation increase in DepE score when compared to a normal subject that does not have a cognitive impairment. 
     
     
         9 . A method for selecting a treatment for improved cognition and/or prevention of cognitive dysfunction/loss by determining a depressive endophenotype (DepE) score comprising:
 performing one or more tests on a subject to determine a depressive endophenotype (DepE), wherein the one or more tests comprise: feeling of worse memory problems, feeling downhearted and blue, feeling worthless, frequently feel like crying, and trouble concentrating; and   selecting a course of treatment for the subject based on whether the subject is scored as having a higher depressive endophenotype when compared to a normal subject that does not have cognitive dysfunction/loss, wherein the treatment is selected from at least one of: an antidepressant, a selective serotonin reuptake inhibitor, a selective serotonin 2C (5-HT2C) antagonist, a serotonin-norepinephrine reuptake inhibitor, or a tricyclic antidepressant.   
     
     
         10 . The method of  claim 9 , wherein a cognitive dysfunction is a disease or condition selected from Alzheimer's Disease, Parkinson's Disease, Down's syndrome, Frontotemporal dementia, Dementia with Lewy Bodies, Multiple sclerosis, traumatic brain injury, depression, schizophrenia, bipolar disease (and other mental illness), diabetes, hypertension, stroke, heart attack, dyslipidemia, other conditions/diseases or aging. 
     
     
         11 . The method of  claim 9 , wherein the DepE score is indicative for Alzheimer's Disease using a receiver operating characteristic (ROC) curve analysis. 
     
     
         12 . The method of  claim 9 , wherein a decrease in the DepE score is indicative of an improvement in at least one of: immediate memory scores and delayed memory scores. 
     
     
         13 . The method of  claim 9 , wherein the treatment is initiated before the subject is diagnosed with Alzheimer's Disease. 
     
     
         14 . The method of  claim 9 , wherein the subject has at least a one standard deviation increase in DepE score when compared to a normal subject that does not have a cognitive impairment. 
     
     
         15 . A method of determining if a drug treats a cognitive dysfunction, the method comprising:
 (a) screening patients into a clinical trial based on tests for a depressive endophenotype (DepE);   (b) administering a candidate drug to a first subset of the patients, and a placebo to a second subset of the patients;   (c) determining if a DepE score predicts a treatment response such that a high depressive endophenotype group responded differentially than a low depressive endophenotype group;   (d) repeating step (a) after administration of the candidate drug or the placebo;   (e) determining if the candidate drug modifies the DepE score over a course of the trial; and   (f) determining if change in the DepE scores over the course of the trial has a positive response, a negative response, or a no treatment response, and if a statistically significant treatment response with the candidate drug is obtained for reducing or preventing the cognitive dysfunction.   
     
     
         16 . The method of  claim 15 , wherein the cognitive dysfunction is a disease or condition selected from Alzheimer's Disease, Parkinson's Disease, Down's syndrome, Frontotemporal dementia, Dementia with Lewy Bodies, Multiple Sclerosis, traumatic brain injury, depression, schizophrenia, bipolar disease (and other mental illness), diabetes, hypertension, stroke, heart attack, dyslipidemia, other conditions/diseases or aging. 
     
     
         17 . The method of  claim 15 , wherein an increase in the DepE score is indicative of an improvement in at least one of: immediate memory scores and delayed memory scores. 
     
     
         18 . The method of  claim 15 , wherein the tests for generating the DepE score comprise one or more of the following: feeling of worse memory problems, feeling downhearted and blue, feeling worthless, frequently feel like crying, and trouble concentrating to determine an elevation of the DepE score. 
     
     
         19 . The method of  claim 15 , wherein elevation of DepE score identifies those eligible for antidepressant therapy for improved cognition or prevention of cognitive loss. 
     
     
         20 . An apparatus for selecting a treatment for improved cognition as well as prevention of cognitive dysfunction/loss with a depressive endophenotype score comprising:
 one or more tests for a subject indicative of the depressive endophenotype;   a processor that obtains an output from the one or more tests, wherein the depressive endophenotype score is calculated using learning machines (random forest, support vector machines), clustering algorithms (factor analysis, principal component analysis), summation of values, or other methods to generate the depressive endophenotype score from the one or more test; and   an output that indicates a course of treatment for the subject based on whether the subject is scored as having the depressive endophenotype, wherein the treatment is selected from at least one of: an antidepressant, a selective serotonin reuptake inhibitor, a selective serotonin 2C (5-HT2C) antagonist, a serotonin-norepinephrine reuptake inhibitor, or a tricyclic antidepressant.