ADNI: Alzheimer's Disease Neuroimaging Initiative

The purpose of this study is to examine how brain imaging technology can be used with other tests to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). This information will aid future clinical trials by providing a standard assessment tool to measure the effects of treatments being studied.

This study will test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The information obtained by studying changes in the brain images of MCI and AD patients and healthy individuals, as well as other assessment tools, will be used to determine the best methods for measuring treatment effects in patients with MCI and AD.

Approximately 800 participants, ranging in age from 55 to 90, will be recruited for the study: 400 patients with MCI, 200 with early AD, and 200 normal controls. Patients with MCI and normal controls will be followed for 3 years, and those with AD will be followed for 2 years. At 6-month intervals, all participants will be seen in person or contacted by telephone. All participants will undergo repeated scanning and blood and urine biomarkers will be collected at the time of each scan. All patients will be asked if they are willing to undergo lumbar puncture at baseline and year one, with the goal of a minimum of 20% and as many as 50% of each group providing CSF (cerebrospinal fluid) samples for analysis and storage for future analyses.

NOTE: Beginning in Spring 2007 a subset of the ADNI participants will be offered the opportunity to participate in a supplemental study. The PIB (Pittsburgh Compound B) study provides imaging of amyloid plaque burden. PIB PET scans will be conducted in 24 control, 48 MCI, and 24 AD participants at approximately 16 ADNI PET sites. For entering participants with no previous PET FDG scans, controls and MCI participants will be scanned with PIB at entry (baseline), 12, 24, and 36 months, and AD participants will be scanned with PIB at entry (baseline), 12, and 24 months. For participants who have undergone previous (baseline and 6 month) PET FDG scans, controls and MCI participants will be scanned with PIB at 12, 24, and 36 months, and AD participants will be scanned with PIB at 12 and 24 months.

community sample

• Procedure: Magnetic Resonance Imaging (MRI)
  MRI scans
• Procedure: Positron Emission Tomography (PET)
  PET scans
• Procedure: Lumbar Puncture (LP)
  collection of cerebrospinal fluid
  Other Name: spinal tap

• 1
  Mild Cognitive Impairment (MCI); scans performed at screening/baseline, 6, 12, 18, 24, and 36 months
  Interventions:

  • Procedure: Magnetic Resonance Imaging (MRI)
  • Procedure: Positron Emission Tomography (PET)
  • Procedure: Lumbar Puncture (LP)
• 2
  Early Alzheimer's disease (AD); scans performed at screening/baseline, 6, 12, and 24 months
  Interventions:

  • Procedure: Magnetic Resonance Imaging (MRI)
  • Procedure: Positron Emission Tomography (PET)
  • Procedure: Lumbar Puncture (LP)
• 3
  Unaffected/normal controls; scans performed at baseline/screening, 6, 12, 24, and 36 months
  Interventions:

  • Procedure: Magnetic Resonance Imaging (MRI)
  • Procedure: Positron Emission Tomography (PET)
  • Procedure: Lumbar Puncture (LP)

• Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD, Rogers J, Siemers E, Trojanowski JQ; National Institute on Aging Biological Markers Working Group. Biological markers for therapeutic trials in Alzheimer's disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer's disease. Neurobiol Aging. 2003 Jul-Aug;24(4):521-36. Review. No abstract available.
• Grundman M, Petersen RC, Ferris SH, Thomas RG, Aisen PS, Bennett DA, Foster NL, Jack CR Jr, Galasko DR, Doody R, Kaye J, Sano M, Mohs R, Gauthier S, Kim HT, Jin S, Schultz AN, Schafer K, Mulnard R, van Dyck CH, Mintzer J, Zamrini EY, Cahn-Weiner D, Thal LJ; Alzheimer's Disease Cooperative Study. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol. 2004 Jan;61(1):59-66.
• Petersen RC. Mild cognitive impairment clinical trials. Nat Rev Drug Discov. 2003 Aug;2(8):646-53. Review. No abstract available.
• Kennedy RE, Schneider LS, Cutter GR, Alzheimer's Disease Neuroimaging Initiative. Biomarker positive and negative subjects in the ADNI cohort: clinical characterization. Curr Alzheimer Res. 2012 Dec;9(10):1135-41.
• Grill JD, Di L, Lu PH, Lee C, Ringman J, Apostolova LG, Chow N, Kohannim O, Cummings JL, Thompson PM, Elashoff D; Alzheimer's Disease Neuroimaging Initiative. Estimating sample sizes for predementia Alzheimer's trials based on the Alzheimer's Disease Neuroimaging Initiative. Neurobiol Aging. 2013 Jan;34(1):62-72. doi: 10.1016/j.neurobiolaging.2012.03.006. Epub 2012 Apr 13.
• Schrag A, Schott JM; Alzheimer's Disease Neuroimaging Initiative. What is the clinically relevant change on the ADAS-Cog? J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):171-3. Epub 2011 Oct 21.
• Samtani MN, Farnum M, Lobanov V, Yang E, Raghavan N, Dibernardo A, Narayan V; Alzheimer’s Disease Neuroimaging Initiative. An improved model for disease progression in patients from the Alzheimer's disease neuroimaging initiative. J Clin Pharmacol. 2012 May;52(5):629-44. Epub 2011 Jun 9.
• Schneider LS, Insel PS, Weiner MW; Alzheimer's Disease Neuroimaging Initiative. Treatment with cholinesterase inhibitors and memantine of patients in the Alzheimer's Disease Neuroimaging Initiative. Arch Neurol. 2011 Jan;68(1):58-66.
• Schneider LS, Kennedy RE, Cutter GR; Alzheimer’s Disease Neuroimaging Initiative. Requiring an amyloid-beta1-42 biomarker for prodromal Alzheimer's disease or mild cognitive impairment does not lead to more efficient clinical trials. Alzheimers Dement. 2010 Sep;6(5):367-77.

Inclusion Criteria:

Participants will be classified as either MCI patients, AD patients, or normal controls. General Inclusion Criteria will apply to all groups, with specific criteria for each group as described below:

General (applies to each category):

• Between 55 and 90 years of age (Currently, ADNI sites are only recruiting volunteers age 70-90 among people with no memory problems)
• Study partner or caregiver to accompany patient to all scheduled visits
• Fluent in English or Spanish
• Permitted medications stable for at least 4 weeks prior to screening
• Adequate visual and auditory acuity to allow neuropsychological testing
• Good general health with no additional diseases expected to interfere with the study
• Women must be two years post-menopausal or surgically sterile
• Willing and able to complete all baseline assessments, and to participate in the 2-3 year protocol
• Willing to undergo neuroimaging and provide DNA and plasma samples as specified
• Completed 6 grades of education or sufficient work history to exclude mental retardation
• Modified Hachinski score <=4
• Geriatric Depression Scale <6

Specific Criteria for MCI and AD patients:

• Memory complaint by patient or study partner
• Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
• Mini-Mental State Exam score between 24 and 30 (MCI) or 20 and 26 (AD)
• Clinical Dementia Rating = 0.5; Memory Box score at least 0.5 (MCI) or 1.0 (AD)

Exclusion Criteria:

• Any significant neurologic disease other than Alzheimer's disease
• Abnormal baseline MRI
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body
• Major depression, bipolar disorder, history of schizophrenia
• History of alcohol or substance abuse or dependency within the past 2 years
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
• Clinically significant laboratory abnormalities
• Residence in skilled nursing facility
• Participation in clinical studies involving neuropsychological measures being collected more than one time per year

Specific Exclusion Criteria for MCI and AD:

• Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.

Prohibited medications:

• Specific psychoactive medications (for example, certain antidepressants, anti-anxiety medications, sleeping pills, etc.)
• Warfarin (Coumadin)
• Investigational agents

• Northern California Institute for Research and Education (NCIRE)
• National Institute on Aging (NIA)
• National Institute for Biomedical Imaging and Bioengineering (NIBIB)
• Foundation for the National Institutes of Health
• Alzheimer’s Drug Discovery Foundation
• Alzheimer's Association