4. Patient Selection Criteria

4.1 Recruitment

Patients will be recruited from the Memory Clinic and the Cognitive Clinic, St James Hospital.  The Memory Clinic in St James’s Hospital functions as a diagnostic centre for memory disorders. Patients who attend this clinic receive standardised clinical assessments including history taking, physical examination, neurological examination, collateral history, neuropsychological tests, routine blood analysis with structural brain imaging (MRI or CT) and, where indicated, in atypical cases, Positron Emission Topography (FDG-PET) or Ioflupane (123I) Scan (DaTScan).

The Cognitive Clinic is ran by the Department of Neurology and receives referrals for early onset neurodegenration and other neurocognitive disorders, often where the diagnosis is unclear. Patients who attend this clinic receive standardised clinical assessments including history taking, physical examination, neurological examination, collateral history, neuropsychological tests, routine blood analysis with structural brain imaging including CT or MRI and where indicated, more advanced imaging modalities may be performed.

This study intends to recruit subjects with possible Alzheimer’s disease where some uncertainty regarding the diagnosis remains, patients with MCI and subjects with early onset neurodegenerative disorders where there may be uncertainly regarding the aetiopathology of the diagnosis over a 12-18 month period.

All subjects will be recruited through the Memory Clinic or the Cognitive Clinic.  All eligible subjects will be asked if they are interested in participating in the research study after they are given the diagnosis of possible Alzheimer’s disease, MCI or early onset neurodegenerative disorder.

A pre-screening visit will be arranged where a study information sheet outlining the study background and aims will be given to each patient and their care giver/ representative. The clinician will complete the Patient Eligibility Screening Form (ESF)[Appendix H] for all potential participants.  This pre-screening visit must take place at least 5 days prior to Visit 1 as participants must be allowed an adequate period of time to review the information provided.

At Visit 1 all participants must sign the study consent forms.

Aim is to recruit 100 subjects with possible Alzheimer’s/ MCI and 50 subjects with early onset neurodegeneration.

4.2 Inclusion Criteria

• Age 45 -90 years overall.

• Patients aged >65 but <90 years,  presenting with possible Alzhimer’s Disease in the early stages where a definitive diagnosis remains unclear but both nueropsychometric testing and neuroimaging findings  are suggestive of the illness.

• Patients aged >65 but <90 years diagnosed with Mild Cognitive Impariment( MCI). MCI is diagnosed according to established clinical consensus criteria[13] and neuropsychological assessments (>1.5 SD memory or non-memory domain). Subjects are classified as having amnesic or non-amnesic MCI and single or multi-domain impairment, depending on the cognitive profile. Disease subtype is diagnosed according to standardized criteria (DSM IV-R) and includes the results of neuroimaging and neuropsychological testing. Cognitive score ≤ 1.5 SD on standardised cognitive tests compared to age-matched normals for MCI.

• Patients aged >45 but <65 years  diagnosed with early onset neurodegenration/dementia (DSM IV-R criteria age <65)

 4.3 Exclusion Criteria

• Psychiatric illness: major depression, bipolar affective disorder and schizophrenia or schizoaffective disorder
• Normal pressure hydrocephalus
• Seizure disorder
• Brain tumour
• Alcohol or drug abuse/dependence (within the past 2 years)
• History of significant head trauma followed by persistent neurologic defaults
• Known structural brain abnormalities
• History of stroke disease
• Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions
• Subjects with multiple lacunes or lacunes in a critical memory structure shown on neuroimaging.
• Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.
• Current use of warfarin (exclusionary for lumbar puncture).

4.4 Control Study Subjects

Cognitively intact aged -matched controls are being recruited from the Santry Sports Clinic where they are undergoing lumber puncture for other indications/ clinical reasons. Ethical approval is in place to allow CSF and blood samples to been taken from these control subjects. These patients provide consent for use of part of their CSF and blood sample for the research study and undergo brief cognitive testing to exclude cognitive impairment- MoCA.