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Longitudinal study on early-onset Alzheimer's disease

Longitudinal Early-onset Alzheimer's Disease Study Protocol

Indiana University · NCT03507257

This study is tracking how early-onset Alzheimer's disease and other cognitive issues develop over time in people aged 40 to 64 to help us understand these conditions better.

Quick facts

Study typeObservational
Enrollment850 (estimated)
Ages40 Years to 64 Years
SexAll
SponsorIndiana University (other)
Drugs / interventionsradiation
Locations23 sites (Sun City, Arizona and 22 other locations)
Trial IDNCT03507257 on ClinicalTrials.gov

What this trial studies

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is an observational study designed to track the progression of cognitive impairment in individuals aged 40 to 64. It includes three cohorts: participants with early onset Alzheimer's Disease (EOAD), those with early onset non-Alzheimer's Disease (EOnonAD), and cognitively normal controls. Participants will undergo a variety of assessments, including clinical evaluations, cognitive tests, biomarker analysis, and neuroimaging over a period of 24 to 48 months. The study aims to collect comprehensive data to better understand the characteristics and progression of early-onset cognitive impairment.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 40-64 with mild cognitive impairment due to Alzheimer's disease or probable Alzheimer's dementia.

Not a fit: Patients with significant memory impairment or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of early-onset Alzheimer's disease and improve future diagnostic and treatment strategies.

How similar studies have performed: Other studies focusing on early-onset Alzheimer's have shown promise, but this specific longitudinal approach is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria for Cognitively Impaired (EOAD and EOnonAD) Cohorts Only:

1. Meets NIA-AA criteria for MCI due to AD or probable AD dementia
2. Have a global CDR score ≤ 1.0
3. Have capacity to provide informed consent (IC) or has a legal authorized representative or guardian who provides IC
4. Age between 40-64 years (inclusive) at the time of consent
5. Must have a study partner (informant) who spends a minimum average of 10 hours per week with the participant (e.g., family member, significant other, friend, caregiver) who is generally aware of the participants' daily activities and can provide information about the participant's cognitive and functional performance. If the participant does not have a study partner who spends at least 10 face-to-face hours per week, other arrangements for identifying a viable study partner will be granted on a case-by-case basis by the Site PI
6. Willing and able to complete longitudinal study procedures aside from LP which is an optional procedure
7. Not pregnant or lactating. Women must be two years post-menopausal, be surgically sterile, or have a negative pregnancy test prior to each PET scan
8. Fluent in English or Spanish if enrolled in the U.S.
9. Fluent in English, Spanish, Dutch or Swedish for sites outside the U.S., according to site's spoken language(s).

Inclusion Criteria for Cognitively Normal (CN) Cohort Only:

1. Meets criteria for cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
2. Have a global CDR score = 0
3. Have capacity to provide informed consent
4. Have a Mini-Mental State Exam score between 26-30 (inclusive). Exceptions may be made for participant with less than 8 years of education at the discretion of the Site PI
5. Age between 40-64 years (inclusive) at the time of consent
6. Must have a study partner (informant) who spends a minimum average of 10 hours per week with the participant (e.g., family member, significant other, friend, caregiver) who is generally aware of the participants' daily activities and can provide information about the participant's cognitive and functional performance. If the participant does not have a study partner who spends 10 face-to-face hours per week, other arrangements for identifying a viable study partner will be granted on a case-by-case basis by the Site PI
7. Willing and able to complete longitudinal study procedures aside from LP which is an optional procedure
8. Not pregnant or lactating. Women must be two years post-menopausal, be surgically sterile, or have a negative pregnancy test prior to each PET scan
9. Fluent in English or Spanish if enrolled in the U.S.
10. Fluent in English, Spanish, Dutch or Swedish for sites outside the U.S., according to site's spoken language(s).

Exclusion Criteria for all (EOAD, EOnonAD and CN) cohorts:

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

Where this trial is running

Sun City, Arizona and 22 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Early Onset Alzheimer Disease, Alzheimer Disease, Mild Cognitive Impairment, Cognitively Normal, Amyloid, Plaques, Neuroimaging, Biomarkers

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.