Resumen

El Estudio Longitudinal de la Enfermedad de Alzheimer de Inicio Temprano (LEADS, por sus siglas en inglés) es un estudio no aleatorizado, de historia natural y sin tratamiento, diseñado para evaluar la progresión de la enfermedad en personas con deterioro cognitivo de inicio temprano. Las características clínicas, cognitivas, de imagen, de biomarcadores y genéticas serán evaluadas en tres cohortes: (1) participantes con Enfermedad de Alzheimer de inicio temprano (EOAD), (2) participantes con enfermedad que no es Alzheimer de inicio temprano (EOnonAD) y (3) participantes cognitivamente normales (CN) como controles.

Descripción detallada

El estudio LEADS es un estudio no aleatorizado, de historia natural y sin tratamiento. Los participantes enrolados deben tener entre 40 y 64 años de edad (inclusive), con deterioro cognitivo leve (DCL) debido a EA o demencia probable por EA (participantes con deterioro cognitivo) o sin deterioro significativo de la memoria (participantes cognitivamente normales [CN]). Aproximadamente 850 participantes con deterioro cognitivo (650 con Enfermedad de Alzheimer de inicio temprano [EOAD] y 200 con enfermedad que no es Alzheimer de inicio temprano [EOnonAD]) y 100 participantes CN serán enrolados en aproximadamente 20 centros en los Estados Unidos. En aproximadamente 5 centros fuera de los Estados Unidos, se enrolarán aproximadamente 400 participantes con deterioro cognitivo y 10 participantes CN. Los participantes con deterioro cognitivo participarán en el estudio durante 48 meses o más; los participantes CN participarán durante 24 meses o más. Los participantes serán sometidos a evaluaciones clínicas y cognitivas longitudinales, pruebas cognitivas computarizadas, pruebas de biomarcadores y genéticas, escaneos de PET (FDG, amiloide y tau) y RM cerebral, y recolección opcional de líquido cefalorraquídeo (LCR). Se invitará a los participantes a considerar la donación cerebral para autopsia. Los objetivos primarios del estudio LEADS son: * Recopilar evaluaciones longitudinales y datos de biomarcadores en personas con deterioro cognitivo de inicio temprano (EOAD / EOnonAD) y controles cognitivamente normales (CN). * Comparar las características cognitivas y funcionales basales y longitudinales entre EOAD y CN, y entre EOAD y la Enfermedad de Alzheimer de inicio tardío (LOAD) de la Iniciativa de Neuroimagen de la Enfermedad de Alzheimer (ADNI). * Estudiar las asociaciones de las evaluaciones clínicas y cognitivas longitudinales con marcadores de imagen multimodal y biofluidos que capturan diferentes elementos de la cascada fisiopatológica de la EA.

Elegibilidad

Edad mínima: 40 YearsEdad máxima: 64 YearsSexo: ALL

Criterios de inclusión

Meets NIA-AA criteria for MCI due to AD or probable AD dementia
Have a global CDR score ≤ 1.0
Have capacity to provide informed consent (IC) or has a legal authorized representative or guardian who provides IC
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 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
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).
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
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).

Criterios de exclusión

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)
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):
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
Deemed ineligible by the Site PI for any other reason

Intervenciones

drug

Flortaucipir

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

Florbetaben

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.

drug

Fluorodeoxyglucose

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.

Protocolo del Estudio Longitudinal de la Enfermedad de Alzheimer de Inicio Temprano

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Flortaucipir

Florbetaben

Fluorodeoxyglucose

Ubicaciones

Fleni

Patrocinadores

Contactos

IU LEADS Team