Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI)
Conditions
Keywords
amyloid, plaques, neuroimaging, biomarkers, cognition disorder, early detection, pre-dementia, dementia, Alzheimer's disease, tau
Brief summary
Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has been realized in informing the design of therapeutic trials in AD. ADNI3 continues the previously funded ADNI-1, ADNI-GO, and ADNI-2 studies that have been combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer's disease (AD). The overall goal of the study is to continue to discover, optimize, standardize, and validate clinical trial measures and biomarkers used in AD research.
Detailed description
The overall goal of ADNI3 is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer's disease (AD), as the pathology evolves from normal aging through very mild symptoms, to mild cognitive impairment (MCI), to dementia. ADNI3 continues the previously funded AD Neuroimaging Initiative (ADNI1, ADNI-GO, and ADNI-2), and remains a public/private collaboration between academia and industry to study biomarkers of AD. ADNI will continue to inform the neuroscience of AD, identify diagnostic and prognostic markers, identify outcome measures that can be used in clinical trials, and help develop the most effective clinical trial scenarios. This is multi-center, a non-randomized, natural history, non-treatment study. 1,070-2,000 total participants will be enrolled across three cohorts: cognitively normal\* (CN), mild cognitive impairment (MCI) and mild Alzheimer's Disease (AD) dementia. Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 700 - 800 will be rollover participants from previous ADNI studies, and 370 - 1200 will be newly enrolled. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts. Participants will undergo longitudinal clinical and cognitive assessments, computerized cognitive batteries, biomarker and genetic tests, PET (FDG, amyloid and tau) and MRI scans and cerebral spinal fluid (CSF) collection for up to 5 years. \*currently recruiting non-Caucasian participants only for the cognitively normal cohort.
Interventions
None listed
Sponsors
University of Southern California
Northern California Institute of Research and Education
National Institute on Aging (NIA)
Alzheimer's Therapeutic Research Institute
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
(all CN participants): 1. Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age 2. Normal memory function documented by scoring above education adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale -Revised (the maximum score is 25): 1. 9 for 16 or more years of education 2. 5 for 8-15 years of education 3. 3 for 0-7 years of education 3. Mini-Mental State Exam score between 24 and 30 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director) 4. Clinical Dementia Rating = 0. Memory Box score must be 0 5. Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living 6. Stability of Permitted Medications for at least 4 weeks: 1. Stable doses of antidepressants lacking significant anticholinergic side effects (if they are currently adequately treated for depressive symptoms and do not have a history of major depression within the past 1 years) 2. Estrogen replacement therapy is permissible 3. Gingko biloba is permissible, but discouraged 4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria (all MCI participants): 1. Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician. 2. Abnormal memory function documented by scoring below education adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale -Revised (the maximum score is 25): a. \< 11 for 16 or more years of education b. ≤ 9 for 8-15 years of education c. ≤ 6 for 0-7 years of education 3. Mini-Mental State Exam score between 24 and 30 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director) 4. Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5 5. General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the Screening Visit 6. Stability of Permitted Medications for at least 4 weeks: 1. Stable doses of antidepressants lacking significant anticholinergic side effects (if they are currently adequately treated for depressive symptoms and do not have a history of major depression within the past 1 years) 2. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to Screening Visit 3. Estrogen replacement therapy is permissible 4. Gingko biloba is permissible, but discouraged 5. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria (all AD participants): 1. Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician.n. 2. Abnormal memory function documented by scoring below education adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale -Revised (the maximum score is 25): 1. ≤ 8 for 16 or more years of education 2. ≤ 4 for 8-15 years of education 3. ≤ 2 for 0-7 years of education 3. Mini-Mental State Exam score between 20 and 26 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director) 4. Clinical Dementia Rating = 0.5 or 1.0 5. NINCDS (National Institute of Neurological and Communicative Disorders and Stroke) -ADRDA (Alzheimer's Disease and Related Disorders Association) criteria for probable AD 6. Stability of Permitted Medications for at least 4 weeks: 1. Stable doses of antidepressants lacking significant anticholinergic side effects (if they are currently adequately treated for depressive symptoms and do not have a history of major depression within the past 1 years) 2. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to Screening Visit 3. Estrogen replacement therapy is permissible 4. Gingko biloba is permissible, but discouraged 5. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria Specific to Newly Enrolled Participants 1. Geriatric Depression Scale score less than 6. 2. Age between 55-90 years (inclusive). 3. Study partner who has frequent contact with the participant (i.e., minimum average of 10 hours per week) and is available to accompany the participant to all clinic visits for the duration of the protocol. 4. Visual and auditory acuity adequate for neuropsychological testing. 5. Good general health with no diseases expected to interfere with the study. 6. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile). 7. Willing and able to participate in a longitudinal imaging study. 8. Modified Hachinski Ischemic Score less than or equal to 4. 9. Completed six grades of education or has a good work history (sufficient to exclude mental retardation). 10. Must speak English or Spanish fluently. 11. Willing to undergo repeated MRIs (3Tesla) and at least two PET scans 12. Agrees to collection of blood for genomic analysis (including GWAS (genome-wide association study) sequencing and other analysis), APOE (Apolipoprotein E) testing and biospecimen banking. 13. Agrees to collection of blood for biomarker testing. 14. Agrees to at least one lumbar puncture for the collection of CSF. 15. Agrees to share genomic data and biomarker samples. Inclusion Criteria Specific to Rollover Participants" The following additional inclusion criteria apply to all diagnostic categories for rollover participants only: 1. Must have been enrolled and followed in ADNI-1, ADNI-GO, or ADNI-2 for at least one year. 2. Willing and able to continue to participate in an ongoing longitudinal study. A reduced battery of tests is allowable if the participant is not able/willing to complete the full battery.
Exclusion criteria
(all CN participants): 1. Any significant neurologic disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13) | 5 years | 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. |
| Rate of change in cognition as measured by the Logical Memory Test I and II | 5 years | — |
| Rate of change in cognition as measured by the Mini-Mental State Examinations (MMSE) | 5 years | The MMSE scale evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of change in cognition as measured by the Cogstate Brief Battery (CBB) | 5 years | The Cogstate Brief battery (CBB) is a brief (10-15 minute) computerized cognitive battery developed by Cogstate (Cogstate Ltd. New Haven, CT, USA) that measures attention, speed of information processing, working memory and learning. |
| Rate of change in cognition as measured by the American National Adult Reading Test (ANART) | 5 years | The ANART estimates premorbid verbal intelligence (VIQ) in patients with dementia. |
| Rate of change in cognition as measured by the Montreal Cognitive Assessment (MoCA) | 5 years | The Montreal Cognitive Assessment test (MoCA) is a cognitive assessment designed to detect participants at the MCI stage of cognitive dysfunction. |
| Rate of change in cognition as measured by the Rey Auditory Verbal Learning Test | 5 years | The AVLT is a list-learning task, which assesses multiple cognitive parameters associated with learning and memory. |
| Rate of change in cognition as measured by the Trail Making Test: A and B | 5 years | — |
| Change in tau deposition as measured by 18F-AV-1451 | 5 years | — |
| Change in amyloid deposition as measured by Florbetapir | 5 years | — |
| Change in amyloid deposition as measured by Florbetaben | 5 years | — |
| Rate of conversion to MCI or dementia due to AD | 5 years | — |
| Rates of change of glucose metabolism (FDG-PET) | 5 years | — |
| Change in Cerebral Spinal Fluid (CSF) Tau Biomarkers | 5 years | — |
| Change in brain structure using magnetic resonance imaging (MRI) | 5 years | — |
Countries
Canada, United States
Contacts
STUDY_DIRECTORMichael W. Weiner, MD
University of California, San Francisco
PRINCIPAL_INVESTIGATORPaul Aisen, MD
USC Alzheimer's Therapeutic Research Institute (ATRI)
PRINCIPAL_INVESTIGATORRonald Peterson, MD, PHD
Mayo Clinic
Outcome results
None listed