Early Onset Alzheimer DiseaseLEADSNCT03507257
Longitudinal Early-onset Alzheimer's Disease Study Protocol
An observational study of Early Onset Alzheimer Disease and Alzheimer Disease, run by Indiana University at 23 sites in 6 countries.
Trial summary
The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a non-randomized, natural history, non-treatment study designed to look at disease progression in individuals with early onset cognitive impairment. Read more about this study
- Who is it for?
- Ages 40 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Early Onset Alzheimer Disease, Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Flortaucipir, Florbetaben and Fluorodeoxyglucose
- Type of treatment
- Injection or infusion
- How many people
- 850 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 30 Apr 2018to 1 Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Cognitively Impaired Participants (ie: Early Onset Alzheimer's Disease (EOAD) and Early Onset non-Alzheimer's Disease (EOnonAD)) and Cognitively Normal (CN) Control Participants
Who may be able to join
- Meets criteria for cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
- Have a global CDR score = 0
- Have capacity to provide informed consent
- 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
- Age between 40-64 years (inclusive) at the time of consent
- 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
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- Willing and able to complete longitudinal study procedures aside from LP which is an optional procedure
- 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
- Fluent in English or Spanish if enrolled in the U.S.
- Fluent in English, Spanish, Dutch or Swedish for sites outside the U.S., according to site's spoken language(s).
Who cannot join
- Meets core clinical criteria for non-AD dementia
- 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
- Known CLIA certified mutation in an ADAD gene (APP, PSEN1, PSEN2), or other autosomal dominant genes associated with other neurodegenerative disorders (MAPT, GRN, C9ORF72)
- 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.)
- 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).
- 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)
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- Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol (at the discretion of the Site PI)
- 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
- Investigational agents are prohibited 30 days prior to entry
- Previous enrollment in a therapeutic trial targeting amyloid or tau.
- 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)
- Lifetime history of schizophrenia spectrum disorders (DSM-5 criteria)
- Current history (in previous 12 months) of DSM-5 diagnosis of mania, bipolar disorder with or without psychotic features
- Current history (in previous 6 months) of moderate or severe substance abuse (nicotine or caffeine is allowed)
- Suicidal behaviors in the past 12 months or active suicidal ideations
- Residing in a 24-hour care skilled nursing facility (at the time of screening)
- (For optional lumbar puncture procedure only):
- 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
- Deemed ineligible by the Site PI for any other reason
Trial locations and contacts
23 sites in 6 countries.
23 sites in 6 countries
United States18 sites
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21218
Massachusetts General Hospital
Boston, Massachusetts, 02114
Northwestern University
Chicago, Illinois, 60611
Houston Methodist Hospital
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 47405
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224
University of California, Los Angeles
Los Angeles, California, 90095
Wien Center
Miami Beach, Florida, 33140
Columbia University
New York, New York, 10032
Stanford University
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Butler Hospital
Providence, Rhode Island, 02906
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
University of California, San Francisco
San Francisco, California, 94121
Washington University, St. Louis
St Louis, Missouri, 63130
Banner Sun Health Research Institute
Sun City, Arizona, 85351
Georgetown University
Washington D.C., District of Columbia, 20057
About this study
The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a non-randomized, natural history, non-treatment study designed to look at disease progression in individuals with early onset cognitive impairment. Clinical, cognitive, imaging, biomarker, and genetic characteristics will be assessed across three cohorts: (1) early onset Alzheimer's Disease (EOAD) participants, (2) early onset non-Alzheimer's Disease (EOnonAD) participants, and (3) cognitively normal (CN) control participants.
Read the detailed description
The LEADS study is a non-randomized, natural history, non-treatment study. Enrolled participants must be 40 - 64 (inclusive) years of age, with MCI due to AD or probable AD dementia (cognitively impaired participants) or have no significant memory impairment (cognitively normal [CN] participants).
Approximately 850 participants with cognitive impairment (650 with early onset Alzheimer's Disease [EOAD] and 200 with early onset non-Alzheimer's Disease [EOnonAD]) and 100 CN participants will be enrolled at approximately 20 sites in the United States. At approximately 5 sites outside of the United States, approximately 400 cognitively impaired participants and 10 CN participants will be enrolled. Cognitively impaired participants will take part in the study for 48+ months; CN participants will take part in the study for 24+ months.
Participants will undergo longitudinal clinical and cognitive assessments, computerized cognitive tests, biomarker and genetic tests, PET (FDG, amyloid and tau) and MRI brain scans, and optional cerebrospinal fluid (CSF) collection. Participants will be invited to consider autopsy brain donation
The primary objectives of the LEADS study are to:
- collect longitudinal assessments and biomarker data in individuals with early onset cognitive impairment (EOAD / EOnonAD) and cognitively normal (CN) controls;
- to compare baseline and longitudinal cognitive and functional characteristics, between EOAD and CN, and EOAD and Late Onset Alzheimer's Disease (LOAD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI); and
- to study the associations of longitudinal clinical and cognitive assessments with multimodal imaging and biofluid markers that capture different elements of the AD pathophysiological cascade
- Being tested
- Flortaucipir, Florbetaben, Fluorodeoxyglucose
- Keywords
- Cognitively Normal, Amyloid, Plaques, Neuroimaging, Biomarkers, Cognition Disorder, Dementia, Tau, Early Onset Alzheimer's Disease, Alzheimer's Disease, Mild Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction, Plaque, Amyloid, Cognition Disorders, Dementia, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlortaucipirDrug
Also called 18F-AV-1451 (also known as [F-18]T807 or LY3191748)
All participants will receive a single bolus intravenous injection of approximately 10 mCi (+/- 10%, 20μg mass dose) of flortaucipir (18F-AV-1451). At approximately 75-minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed.
FlorbetabenDrug
Also called AV-45, Neuraceq
All participants will receive a single bolus intravenous injection of approximately 8 mCi +/- .8mCi of florbetaben (AV-45). At approximately 90-minutes (+/- 10 minutes) post dose, scanning will begin. An approximately 20-minute image acquisition scan will be performed.
FluorodeoxyglucoseDrug
Also called FDG
All participants will receive a single bolus intravenous injection of approximately 5 mCi (+/- 10%, 0.5 mCi) of fluorodeoxyglucose. At approximately 30 minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed.
| Study group | Role | What they receive |
|---|---|---|
| Early Onset Alzheimer's Disease (EOAD) | * Diagnosis of NIA-AA criteria of MCI due to AD or probable AD dementia
* Amyloid positive status (florbetaben PET scan with evidence of elevated amyloid as determined by a central read)
* CDR score ≤ 1.0
* flortaucipir (18F-AV-1451) PET scanning Receives: Drug: Flortaucipir; Drug: Florbetaben | |
| Cognitively Normal (CN) Controls | * Meets criteria for cognitively normal, based on an absence of significant impairment in cognitive functions and activities of daily living
* Mini-Mental State Exam score between 26-30
* CDR score = 0
* flortaucipir (18F-AV-1451) PET scanning Receives: Drug: Flortaucipir; Drug: Florbetaben; Drug: Fluorodeoxyglucose | |
| Early Onset non-Alzheimer's Disease (EOnonAD) | * Diagnosis of NIA-AA criteria of MCI due to AD or probable AD dementia
* Amyloid negative status (florbetaben PET scan with no evidence of elevated amyloid as determined by a central read)
* CDR score ≤ 1.0
* flortaucipir (18F-AV-1451) PET scanning Receives: Drug: Flortaucipir; Drug: Florbetaben; Drug: Fluorodeoxyglucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)
The ADAS-Cog is an in-person examiner-administered, structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained.
Measured: Month 0, Month 12, Month 24, Month 36 (EOAD/EOnonAD only) and Month 48 (EOAD/EOnonAD only)
Secondary outcomes (7)
Rate of change in cognition as measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB)
The CDR is a semi-structured interview of the informant and participant that assesses for impairment in 8 areas of functioning - memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care, behavior, personality, and language.
Measured: CN participants: Month 0 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24, Month 36 and Month 48
Change in tau deposition as measured by flortaucipir (18F-AV-1451) Positron Emission Tomography (PET) imaging
Measured: Month 0, Month 12 (EOAD only), Month 24 (EOAD only) and Month 36 (EOAD and EOnonAD amyloid positive participants only)
Change in amyloid deposition as measured by florbetaben using Positron Emission Tomography (PET) imaging
Measured: Month 0, Month 12 (EOAD only), Month 24 (EOAD only) and Month 36 (EOAD/EOnonAD only
Neurodegeneration as measured by fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) imaging compared to magnetic resonance imaging (MRI)
Measured: Month 12 (EOnonAD only) and Month 24 (CN only)
Change in brain structure using magnetic resonance imaging (MRI)
Measured: CN participants: Month 0 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24 and Month 36
Change in cerebrospinal fluid (CSF) biomarkers
Measured: CN participants: Month 0 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24, Month 36
Change in plasma biomarkers
Measured: CN participants: Month 0, Month 12 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24, Month 36 and Month 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2018
- Study start30 Apr 2018
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (57)Papers the sponsor has linked to this study.
- Other trials for Early Onset Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 850 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer's Therapeutic Research Institute, National Institute on Aging (NIA), Alzheimer's Association
- Responsible party
- Principal investigator, Liana Apostolova, Indiana University
- Investigators
- Liana Apostolova, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03507257
- Sponsor's protocol ID
- ATRI-003
- Other IDs
- R56AG057195
- Acronym
- LEADS
- Status last verified
- Jul 2026
- First submitted
- 4 Apr 2018
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study data will be shared broadly through the Laboratory of NeuroImaging (LONI), with aggregate data sharing through the Global Alzheimer's Association Interactive Network (GAAIN). MRI and PET data will also be available for download from the LEADS Image and Data Archive (IDA) website. Genetics, genomics, and related data will be shared with other researchers pursuant to the NIA Genetics Sharing Policy. National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site, with other NIA-approved sites, will make genetic, genomic and related data and associated phenotypic data available to qualified investigators for secondary analysis in accordance with standards established by NIA.
Publications
Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C; Medical Research Council Cognitive Function and Ageing Study. Age, neuropathology, and dementia. N Engl J Med. 2009 May 28;360(22):2302-9. doi: 10.1056/NEJMoa0806142.
PubMed 19474427Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007 Dec 11;69(24):2197-204. doi: 10.1212/01.wnl.0000271090.28148.24. Epub 2007 Jun 13.
PubMed 17568013Szigeti K, Doody RS. Should EOAD patients be included in clinical trials? Alzheimers Res Ther. 2011 Feb 8;3(1):4. doi: 10.1186/alzrt63.
PubMed 21345175Wingo TS, Lah JJ, Levey AI, Cutler DJ. Autosomal recessive causes likely in early-onset Alzheimer disease. Arch Neurol. 2012 Jan;69(1):59-64. doi: 10.1001/archneurol.2011.221. Epub 2011 Sep 12.
PubMed 21911656Koedam EL, Lauffer V, van der Vlies AE, van der Flier WM, Scheltens P, Pijnenburg YA. Early-versus late-onset Alzheimer's disease: more than age alone. J Alzheimers Dis. 2010;19(4):1401-8. doi: 10.3233/JAD-2010-1337.
PubMed 20061618Mendez MF, Lee AS, Karve SJ, Shapira JS. Nonamnestic presentations of early-onset Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2012 Sep;27(6):413-20. doi: 10.1177/1533317512454711. Epub 2012 Aug 7.
PubMed 22871906Snowden JS, Stopford CL, Julien CL, Thompson JC, Davidson Y, Gibbons L, Pritchard A, Lendon CL, Richardson AM, Varma A, Neary D, Mann D. Cognitive phenotypes in Alzheimer's disease and genetic risk. Cortex. 2007 Oct;43(7):835-45. doi: 10.1016/s0010-9452(08)70683-x.
PubMed 17941342Jacobs D, Sano M, Marder K, Bell K, Bylsma F, Lafleche G, Albert M, Brandt J, Stern Y. Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology. 1994 Jul;44(7):1215-20. doi: 10.1212/wnl.44.7.1215.
PubMed 8035918Koss E, Edland S, Fillenbaum G, Mohs R, Clark C, Galasko D, Morris JC. Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: A CERAD analysis, Part XII. Neurology. 1996 Jan;46(1):136-41. doi: 10.1212/wnl.46.1.136.
PubMed 8559362Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76. doi: 10.1016/j.jalz.2012.11.008. Epub 2013 Feb 12.
PubMed 23411393Frisoni GB, Testa C, Sabattoli F, Beltramello A, Soininen H, Laakso MP. Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study. J Neurol Neurosurg Psychiatry. 2005 Jan;76(1):112-4. doi: 10.1136/jnnp.2003.029876.
PubMed 15608008Kim EJ, Cho SS, Jeong Y, Park KC, Kang SJ, Kang E, Kim SE, Lee KH, Na DL. Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients. Brain. 2005 Aug;128(Pt 8):1790-801. doi: 10.1093/brain/awh539. Epub 2005 May 11.
PubMed 15888536Rabinovici GD, Furst AJ, Alkalay A, Racine CA, O'Neil JP, Janabi M, Baker SL, Agarwal N, Bonasera SJ, Mormino EC, Weiner MW, Gorno-Tempini ML, Rosen HJ, Miller BL, Jagust WJ. Increased metabolic vulnerability in early-onset Alzheimer's disease is not related to amyloid burden. Brain. 2010 Feb;133(Pt 2):512-28. doi: 10.1093/brain/awp326. Epub 2010 Jan 15.
PubMed 20080878Lehmann M, Ghosh PM, Madison C, Laforce R Jr, Corbetta-Rastelli C, Weiner MW, Greicius MD, Seeley WW, Gorno-Tempini ML, Rosen HJ, Miller BL, Jagust WJ, Rabinovici GD. Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease. Brain. 2013 Mar;136(Pt 3):844-58. doi: 10.1093/brain/aws327. Epub 2013 Jan 28.
PubMed 23358601Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011 Sep;10(9):785-96. doi: 10.1016/S1474-4422(11)70156-9. Epub 2011 Jul 27.
PubMed 21802369
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Early-onset Alzheimer's Disease Study Protocol
- ClinicalTrials.gov ID
- NCT03507257
- Acronym / sponsor ID
- LEADS / ATRI-003
- Keywords
- Cognitively Normal, Amyloid, Plaques, Neuroimaging, Biomarkers, Cognition Disorder, Dementia, Tau
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 850 participants (estimated)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Alzheimer's Therapeutic Research Institute, National Institute on Aging (NIA), Alzheimer's Association
- Study start
- 30 Apr 2018 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 25 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a non-randomized, natural history, non-treatment study designed to look at disease progression in individuals with early onset cognitive impairment. Clinical, cognitive, imaging, biomarker, and genetic characteristics will be assessed across three cohorts: (1) early onset Alzheimer's Disease (EOAD) participants, (2) early onset non-Alzheimer's Disease (EOnonAD) participants, and (3) cognitively normal (CN) control participants.
Detailed description
The LEADS study is a non-randomized, natural history, non-treatment study. Enrolled participants must be 40 - 64 (inclusive) years of age, with MCI due to AD or probable AD dementia (cognitively impaired participants) or have no significant memory impairment (cognitively normal [CN] participants).
Approximately 850 participants with cognitive impairment (650 with early onset Alzheimer's Disease [EOAD] and 200 with early onset non-Alzheimer's Disease [EOnonAD]) and 100 CN participants will be enrolled at approximately 20 sites in the United States. At approximately 5 sites outside of the United States, approximately 400 cognitively impaired participants and 10 CN participants will be enrolled. Cognitively impaired participants will take part in the study for 48+ months; CN participants will take part in the study for 24+ months.
Participants will undergo longitudinal clinical and cognitive assessments, computerized cognitive tests, biomarker and genetic tests, PET (FDG, amyloid and tau) and MRI brain scans, and optional cerebrospinal fluid (CSF) collection. Participants will be invited to consider autopsy brain donation
The primary objectives of the LEADS study are to:
- collect longitudinal assessments and biomarker data in individuals with early onset cognitive impairment (EOAD / EOnonAD) and cognitively normal (CN) controls;
- to compare baseline and longitudinal cognitive and functional characteristics, between EOAD and CN, and EOAD and Late Onset Alzheimer's Disease (LOAD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI); and
- to study the associations of longitudinal clinical and cognitive assessments with multimodal imaging and biofluid markers that capture different elements of the AD pathophysiological cascade
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Early Onset Alzheimer's Disease (EOAD) | – | Drug: Flortaucipir, Drug: Florbetaben* Diagnosis of NIA-AA criteria of MCI due to AD or probable AD dementia * Amyloid positive status (florbetaben PET scan with evidence of elevated amyloid as determined by a central read) * CDR score ≤ 1.0 * flortaucipir (18F-AV-1451) PET scanning |
| Cognitively Normal (CN) Controls | – | Drug: Flortaucipir, Drug: Florbetaben, Drug: Fluorodeoxyglucose* Meets criteria for cognitively normal, based on an absence of significant impairment in cognitive functions and activities of daily living * Mini-Mental State Exam score between 26-30 * CDR score = 0 * flortaucipir (18F-AV-1451) PET scanning |
| Early Onset non-Alzheimer's Disease (EOnonAD) | – | Drug: Flortaucipir, Drug: Florbetaben, Drug: Fluorodeoxyglucose* Diagnosis of NIA-AA criteria of MCI due to AD or probable AD dementia * Amyloid negative status (florbetaben PET scan with no evidence of elevated amyloid as determined by a central read) * CDR score ≤ 1.0 * flortaucipir (18F-AV-1451) PET scanning |
Who may qualify
- Ages
- 40 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Cognitively Impaired Participants (ie: Early Onset Alzheimer's Disease (EOAD) and Early Onset non-Alzheimer's Disease (EOnonAD)) and Cognitively Normal (CN) Control Participants
Key inclusion criteria (10 listed)
- Meets criteria for cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
- Have a global CDR score = 0
- Have capacity to provide informed consent
- 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
- Age between 40-64 years (inclusive) at the time of consent
Key exclusion criteria (19 listed)
- Meets core clinical criteria for non-AD dementia
- 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
- Known CLIA certified mutation in an ADAD gene (APP, PSEN1, PSEN2), or other autosomal dominant genes associated with other neurodegenerative disorders (MAPT, GRN, C9ORF72)
- 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.)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FlortaucipirAlso: 18F-AV-1451 (also known as [F-18]T807 or LY3191748)All participants will receive a single bolus intravenous injection of approximately 10 mCi (+/- 10%, 20μg mass dose) of flortaucipir (18F-AV-1451). At approximately 75-minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed. | Drug | Cognitively Normal (CN) Controls, Early Onset Alzheimer's Disease (EOAD), Early Onset non-Alzheimer's Disease (EOnonAD) |
| FlorbetabenAlso: AV-45, NeuraceqAll participants will receive a single bolus intravenous injection of approximately 8 mCi +/- .8mCi of florbetaben (AV-45). At approximately 90-minutes (+/- 10 minutes) post dose, scanning will begin. An approximately 20-minute image acquisition scan will be performed. | Drug | Cognitively Normal (CN) Controls, Early Onset Alzheimer's Disease (EOAD), Early Onset non-Alzheimer's Disease (EOnonAD) |
| FluorodeoxyglucoseAlso: FDGAll participants will receive a single bolus intravenous injection of approximately 5 mCi (+/- 10%, 0.5 mCi) of fluorodeoxyglucose. At approximately 30 minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed. | Drug | Cognitively Normal (CN) Controls, Early Onset non-Alzheimer's Disease (EOnonAD) |
Primary outcome
Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)
Time frame: Month 0, Month 12, Month 24, Month 36 (EOAD/EOnonAD only) and Month 48 (EOAD/EOnonAD only)
The ADAS-Cog is an in-person examiner-administered, structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained.
7 secondary outcomes
Rate of change in cognition as measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB)
Time frame: CN participants: Month 0 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24, Month 36 and Month 48
Change in tau deposition as measured by flortaucipir (18F-AV-1451) Positron Emission Tomography (PET) imaging
Time frame: Month 0, Month 12 (EOAD only), Month 24 (EOAD only) and Month 36 (EOAD and EOnonAD amyloid positive participants only)
Change in amyloid deposition as measured by florbetaben using Positron Emission Tomography (PET) imaging
Time frame: Month 0, Month 12 (EOAD only), Month 24 (EOAD only) and Month 36 (EOAD/EOnonAD only
Neurodegeneration as measured by fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) imaging compared to magnetic resonance imaging (MRI)
Time frame: Month 12 (EOnonAD only) and Month 24 (CN only)
Change in brain structure using magnetic resonance imaging (MRI)
Time frame: CN participants: Month 0 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24 and Month 36
Change in cerebrospinal fluid (CSF) biomarkers
Time frame: CN participants: Month 0 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24, Month 36
Change in plasma biomarkers
Time frame: CN participants: Month 0, Month 12 and Month 24; EOAD/EOnonAD participants: Month 0, Month 12, Month 24, Month 36 and Month 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Background: PubMed 19474427Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C; Medical Research Council Cognitive Function and Ageing Study. Age, neuropathology, and dementia. N Engl J Med. 2009 May 28;360(22):2302-9. doi: 10.1056/NEJMoa0806142.
- Background: PubMed 17568013Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007 Dec 11;69(24):2197-204. doi: 10.1212/01.wnl.0000271090.28148.24. Epub 2007 Jun 13.
- Background: PubMed 21345175Szigeti K, Doody RS. Should EOAD patients be included in clinical trials? Alzheimers Res Ther. 2011 Feb 8;3(1):4. doi: 10.1186/alzrt63.
- Background: PubMed 21911656Wingo TS, Lah JJ, Levey AI, Cutler DJ. Autosomal recessive causes likely in early-onset Alzheimer disease. Arch Neurol. 2012 Jan;69(1):59-64. doi: 10.1001/archneurol.2011.221. Epub 2011 Sep 12.
- Background: PubMed 20061618Koedam EL, Lauffer V, van der Vlies AE, van der Flier WM, Scheltens P, Pijnenburg YA. Early-versus late-onset Alzheimer's disease: more than age alone. J Alzheimers Dis. 2010;19(4):1401-8. doi: 10.3233/JAD-2010-1337.
- Background: PubMed 22871906Mendez MF, Lee AS, Karve SJ, Shapira JS. Nonamnestic presentations of early-onset Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2012 Sep;27(6):413-20. doi: 10.1177/1533317512454711. Epub 2012 Aug 7.
- Background: PubMed 17941342Snowden JS, Stopford CL, Julien CL, Thompson JC, Davidson Y, Gibbons L, Pritchard A, Lendon CL, Richardson AM, Varma A, Neary D, Mann D. Cognitive phenotypes in Alzheimer's disease and genetic risk. Cortex. 2007 Oct;43(7):835-45. doi: 10.1016/s0010-9452(08)70683-x.
- Background: PubMed 8035918Jacobs D, Sano M, Marder K, Bell K, Bylsma F, Lafleche G, Albert M, Brandt J, Stern Y. Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology. 1994 Jul;44(7):1215-20. doi: 10.1212/wnl.44.7.1215.
- Background: PubMed 8559362Koss E, Edland S, Fillenbaum G, Mohs R, Clark C, Galasko D, Morris JC. Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: A CERAD analysis, Part XII. Neurology. 1996 Jan;46(1):136-41. doi: 10.1212/wnl.46.1.136.
- Background: PubMed 23411393Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76. doi: 10.1016/j.jalz.2012.11.008. Epub 2013 Feb 12.
- Background: PubMed 15608008Frisoni GB, Testa C, Sabattoli F, Beltramello A, Soininen H, Laakso MP. Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study. J Neurol Neurosurg Psychiatry. 2005 Jan;76(1):112-4. doi: 10.1136/jnnp.2003.029876.
- Background: PubMed 15888536Kim EJ, Cho SS, Jeong Y, Park KC, Kang SJ, Kang E, Kim SE, Lee KH, Na DL. Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients. Brain. 2005 Aug;128(Pt 8):1790-801. doi: 10.1093/brain/awh539. Epub 2005 May 11.
- Individual participant dataSharing planned: Yes. Study data will be shared broadly through the Laboratory of NeuroImaging (LONI), with aggregate data sharing through the Global Alzheimer's Association Interactive Network (GAAIN). MRI and PET data will also be available for download from the LEADS Image and Data Archive (IDA) website. Genetics, genomics, and related data will be shared with other researchers pursuant to the NIA Genetics Sharing Policy. National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site, with other NIA-approved sites, will make genetic, genomic and related data and associated phenotypic data available to qualified investigators for secondary analysis in accordance with standards established by NIA.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liana Apostolova, MD principal investigator
Indiana University
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Early Onset Alzheimer Disease and Alzheimer Disease, run by Indiana University at 23 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Argentina, Netherlands, Spain, Sweden and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13) (time frame: Month 0, Month 12, Month 24, Month 36 (EOAD/EOnonAD only) and Month 48 (EOAD/EOnonAD only)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03507257, which also lists 57 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.