Effect of Cerefolin®/CerefolinNAC® on Biomarker Measurements

Study Overview
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Brief Summary
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In a retrospective analysis of data from 1100 patients, disease-delaying effects of Cerefolin®/CerefolinNAC® were examined in terms of cognition. The purpose of the current study is to expand the retrospective study dataset by prospectively collecting additional biomarker and imaging data.

Detailed Description
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CerefolinNAC® is an orally administered prescription medical food, and is formulated as a combination of L-methylfolate calcium (as Metafolin®), methylcobalamin, and N-acetylcysteine. In a retrospective analysis, disease-delaying effects of Cerefolin®/CerefolinNAC® (CFLN) are examined in terms of cognition (measured by MCI Screen (MCIS)), and functional capacity (measured by Functional Assessment Staging Test (FAST)). - the treatment effect of CFLN on cognitive and functional measures, and on biomarker measures in patients with Alzheimer's disease and related disorders (ADRD). The current study will expand the NAC-002b study dataset by prospectively collecting additional biomarker and imaging data in a more comprehensively assessed, matched sample of patients. This will allow more precise evaluation of cognitive and functional outcome measures, and biomarker measures will be assessed in an attempt to identify specific populations or conditions in which CFLN is most effective. The sample will consist of patients with homocysteinemia plus past/current CFLN treatment (Treatment Group) matched to those without homocysteinemia plus no past/current B12, folate or CFLN treatment (Non-Treatment Group). Also 65 additional subjects will be recruited for the non-Treatment group, which will be used to improve the rate of decline estimates for the cognitive and functional outcome measures.

Official Title
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Effect of Cerefolin®/CerefolinNAC® on Biomarker Measurements in Patients With Mild Cognitive Impairment, Alzheimer's Disease and Related Disorders

Conditions
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Mild Cognitive Impairment, Alzheimer's Disease, Alzheimer's Disease Related Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a diagnosis of normal aging (NL), cognitive impairment or dementia not otherwise specified (CI/D), or ADRD With at least one previous quantitative MRI (qMRI) With at least one previous homocysteine level Without homocysteinemia plus no past or current B12, folate or Cerefolin® treatment, OR with homocysteinemia plus past or current Cerefolin® treatment Exclusion Criteria: Subjects who do not meet the inclusion criteria will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment Group<br>This group consists of patients diagnosed with homocysteinemia who have been treated with Cerefolin®/CerefolinNAC® in the past or are currently being treated with Cerefolin®/CerefolinNAC®. | |
| Non-Treatment Group<br>This group consists of patients not diagnosed with homocysteinemia who have no past or current treatment with Vitamin B12, Folate or Cerefolin®/CerefolinNAC®. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in rate of cognitive decline as measured by the Memory Performance Index (MPI) | Change in MPI over time will be calculated using multiple retrospective time points. | Baseline to end of study (estimated average of 48 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in rate of cognitive decline as measured by the MCI Screen | Change in MCI Screen over time will be calculated using multiple retrospective time points. | Baseline to end of study (estimated average of 48 months) | 
| Change in rate of cognitive decline as measured by The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Drawings | Change in CERAD drawings over time will be evaluated using multiple retrospective time points | Baseline to end of study (estimated average of 48 months) | 
| Change in rate of cognitive decline as measured by Trails A & B | Change in Trails A & B over time will be assessed using multiple retrospective time points | Baseline to end of study (estimated average of 48 months) | 
| Rate of atrophy of hippocampal volume | Decrease in hippocampal volume over time will be assessed using volumetric MRI | Baseline to end of study (estimated average of 48 months) | 
| Rate of atrophy in cortical volume | Decrease in cortical volume over time will be assessed using volumetric MRI | Baseline to end of study (estimated average of 48 months) | 
| Rate of atrophy in ventricular volume | Decrease in ventricular volume over time will be assessed using volumetric MRI | Baseline to end of study (estimated average of 48 months) | 
| Change in rate of cognitive decline as measured by Functional Assessment Staging Test (FAST) | Change in FAST over time will be calculated using multiple retrospective time points. | Baseline to end of study (estimated average of 48 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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homocysteinemia, dementia, depression, vitamin B12, folate, mild cognitive impairment, alzheimer's, homocysteine