Effect of Cerefolin®/CerefolinNAC® on Biomarker Measurements

• Change in rate of cognitive decline as measured by the Memory Performance Index (MPI) [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Change in MPI over time will be calculated using multiple retrospective time points.
  
  

• Change in rate of cognitive decline as measured by the MCI Screen [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Change in MCI Screen over time will be calculated using multiple retrospective time points.
  
  
• Change in rate of cognitive decline as measured by The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Drawings [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Change in CERAD drawings over time will be evaluated using multiple retrospective time points
  
  
• Change in rate of cognitive decline as measured by Trails A & B [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Change in Trails A & B over time will be assessed using multiple retrospective time points
  
  
• Rate of atrophy of hippocampal volume [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Decrease in hippocampal volume over time will be assessed using volumetric MRI
  
  
• Rate of atrophy in cortical volume [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Decrease in cortical volume over time will be assessed using volumetric MRI
  
  
• Rate of atrophy in ventricular volume [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Decrease in ventricular volume over time will be assessed using volumetric MRI
  
  
• Change in rate of cognitive decline as measured by Functional Assessment Staging Test (FAST) [ Time Frame: Baseline to end of study (estimated average of 48 months) ] [ Designated as safety issue: No ]
  Change in FAST over time will be calculated using multiple retrospective time points.
  
  

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.