Longitudinal Early-onset Alzheimer's Disease Study Protocol

Exclusion Criteria

• •1. Meets core clinical criteria for non-AD dementia
• •2. Two or more first degree relatives with a history of early-onset dementia suggestive of autosomal dominant transmission, unless known pathogenic mutations in APP, PSEN1, PSEN2, MAPT, GRN and C9ORF72 have been excluded
• •3. Known CLIA certified mutation in an ADAD gene (APP, PSEN1, PSEN2), or other autosomal dominant genes associated with other neurodegenerative disorders (MAPT, GRN, C9ORF72)
• •4. Contraindications to 3T MRI (e.g., claustrophobia, pacemaker, select aneurismal clip, artificial heart valve, select ear implants, select stents incompatible with 3T MRI, metal fragments or foreign objects in the eyes, skin or body, etc.)
• •5. Lifetime medical history of a brain disorder other than the disorder causing dementia except for headache (exceptions are allowed at the discretion of the Site PI - e.g., seizure disorder thought to be due to EOAD).
• •6. MRI scan with evidence of infection or focal lesions, cortical strokes, multiple lacunes (single lacune is allowable unless it meets criteria for strategic lacune affecting cognition)
• •7. Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol (at the discretion of the Site PI)
• •8. Research radiation exposure will be assessed by the study physician. If the candidate participant has had more than one nuclear medicine study in the prior 12 months for research-related purposes, study inclusion will require approval from the PET Core
• •9. Investigational agents are prohibited 30 days prior to entry
• •10. Previous enrollment in a therapeutic trial targeting amyloid or tau.
• •11. Participation in other clinical studies with neuropsychological measures, with the exception of participants who are co-enrolled in the NACC Uniform Data Set (UDS) protocol (Note: This criterion is intended to reduce repeat measures effects during neuropsychological testing. Exceptions are allowed at the discretion of the Site PI)
• •12. Lifetime history of schizophrenia spectrum disorders (DSM-5 criteria)
• •13. Current history (in previous 12 months) of DSM-5 diagnosis of mania, bipolar disorder with or without psychotic features
• •14. Current history (in previous 6 months) of moderate or severe substance abuse (nicotine or caffeine is allowed)
• •15. Suicidal behaviors in the past 12 months or active suicidal ideations
• •16. Residing in a 24-hour care skilled nursing facility (at the time of screening)
• •17. (For optional lumbar puncture procedure only):
• •a. Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be not clinically significant by the Site PI i. Platelet count \<100,000/ml ii. INR\>1.2 iii. Abnormal PT or PTT at screening b. Contraindications to the procedure, including but not limited to severe degenerative joint disease, deformity of the spine, history of a bleeding disorder c. Suspected elevated intracranial pressure, Arnold Chiari malformation or mass lesion d. Use of the anticoagulant medications such as but not limited to warfarin, rivaroxaban, dabigatran
• •18. Deemed ineligible by the Site PI for any other reason