3. Objectives

3.1 Study Aims

The aims of this study are, in an Irish cohort:

• to explore the utility of CSF biomarkers in the prediction of conversion of subjects with MCI to dementia .
• to explore the significance of CSF biomarkers levels in the early stages of possible Alzheimer’s disease and if these measurements can contribute to establishing a more definitive diagnosis at an earlier stage of the disease trajectory.
• to determine the utility of CSF biomarkers as an adjunct in the delineation of the aetiopathology of early onset neurodegenerative disorders, where there is an atypical pattern of cognitive impairment and uncertainty regarding the clinical diagnosis.
• in the context of the BIOMARKAPD project research aims, to examine a range of standardization issues with respect to biomarker analysis in CSF and investigate ways to rectify inconsistencies in  biomarkers measurement method between labs in different countries.
• to explore the utility of measuring  β- amyloid  protein fragments and other biomarkers in blood, in predicting and monitoring cognitive  decline and progression to AD in subjects with MCI.

3.2 Study Endpoints

For all patient cohorts the study endpoints consist of:

• Decline on cognitive and functional measures (RBANS, MoCA, ADL)
• Development of dementia as defined by the standard criteria (DSM- IV-R).

If a subject with possible/ mild Alzheimer’s disease is re-assessed and a more definitive diagnosis of Alzheimer’s disease is made, the subject’s participation in the study will end (study endpoint).

If a subject with MCI transitions to dementia (Alzheimer’s disease) during the duration of the study, the subject’s participation in the study will end (study endpoint). The NINCDS/ ADRDA Criteria for probable Alzheimer’s Disease will be used to establish whether a subjects meet the criteria for the diagnosis of probable Alzheimer’s disease [12] [Appendix E ]

If a subject with early onset neurodegeneration progresses and a diagnosis becomes more clear with time and their cognitive deficits are not due to Alzheimer’s Dementia, their participation in the study will end (study endpoint).

If a subject is withdrawn from the study at any point during the study duration, this will not in anyway impact on their follow-up and care at the clinic they are attending (Memory clinic or Cognitive Clinic).