Evolution of Memory Related Activity

NCT ID: NCT00902499

Last Updated: 2010-07-26

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 160 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2011-05-31

Brief Summary

The purpose of this study is to begin the process of validating fMRI (functional magnetic resonance imaging) as a biomarker for use in clinical trials and longitudinal studies of clinical progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Detailed Description

The development of biomarkers is now especially critical, as there are a number of promising disease-modifying therapies entering early phase clinical trials, with additional novel therapeutic strategies in development. It is essential to develop biomarkers that can detect a "signal of efficacy" over a relatively short time frame for use in Phase II trials. Ideally biomarkers are needed that can reliably detect the earliest brain alterations due to AD pathology, perhaps at a point when there is synaptic dysfunction but not yet widespread neuronal loss. Functional neuroimaging, in particular functional MRI (fMRI), has significant potential, having already shown promise in detecting regionally specific pharmacological effects on memory related neural activity, and as a sensitive marker of very early cognitive impairment.

This study, a parallel ancillary study of the Alzheimer's Disease Neuroimaging Initiative (ADNI), will first examine reproducibility of fMRI activation, using a face-name associative memory paradigm, and then the alterations in memory-related activation that occur over the course of MCI and mild AD. The study will also examine the relationship of fMRI activation to clinical variables, memory task performance, genotype, and other imaging techniques cross-sectionally and longitudinally, sampling at multiple time points over a 3-year period.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

NC

Normal older controls, not cognitively impaired; MMSE 27-30 and performance above education adjusted cutoff scores on the Logical Memory II subscale (LM-II Delayed Paragraph Recall) of the Wechsler Memory Scale

No interventions assigned to this group

vMCI

Very mild cognitive impairment; less severe objective memory deficit, scoring .5 to 1.5 S.D. (standard deviation) below education adjusted norms on the LM-II

No interventions assigned to this group

sMCI

significant mild cognitive impairment; objective cut off of 1.5 S.D. level below education adjusted norms on the LM-II

No interventions assigned to this group

AD

Mild Alzheimer's disease; meet NINCDS/ADRDA criteria for probable AD with mild dementia severity (CDR Total = 1), MMSE 20-26

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Ages 55-90
• General good health or stable medical problems
• Study partner/caregiver able to provide an independent evaluation of the participant's daily functioning
• No contraindications to MR scanning
• Modified Hachinski Ischemic Score ≤4
• Geriatric Depression Scale ≤10

Exclusion Criteria

• Diagnosis of Parkinson's disease or other neurological illness
• Presence of clinically significant/uncontrolled medical conditions
• History of stroke, brain tumor, brain surgery, seizures, significant head trauma with loss of consciousness, depression or other psychiatric illness, alcohol or drug abuse in the past 2 years
• Significant uncorrectable visual impairment

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: lead

Responsible Party

Brigham and Women's Hospital

Principal Investigators

Reisa Sperling, MD

Role: PRINCIPAL_INVESTIGATOR

Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Caroline Sullivan

Role: CONTACT

csullivan21@partners.org

617-726-6212

Meghan Frey

Role: CONTACT

mfrey1@partners.org

617-732-8085

Facility Contacts

Meghan Frey

Role: primary

mfrey1@partners.org

617-732-8085

Caroline Sullivan

Role: primary

csullivan21@partners.org

617-726-6212

References

Sperling R, Greve D, Dale A, Killiany R, Holmes J, Rosas HD, Cocchiarella A, Firth P, Rosen B, Lake S, Lange N, Routledge C, Albert M. Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):455-60. doi: 10.1073/pnas.012467899. Epub 2001 Dec 26.

Reference Type: BACKGROUND

PMID: 11756667 (View on PubMed)

Sperling RA, Bates JF, Chua EF, Cocchiarella AJ, Rentz DM, Rosen BR, Schacter DL, Albert MS. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2003 Jan;74(1):44-50. doi: 10.1136/jnnp.74.1.44.

Reference Type: BACKGROUND

PMID: 12486265 (View on PubMed)

Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42. doi: 10.1073/pnas.0308627101. Epub 2004 Mar 15.

Reference Type: BACKGROUND

PMID: 15070770 (View on PubMed)

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. doi: 10.1001/archneur.61.1.59.

Reference Type: BACKGROUND

PMID: 14732621 (View on PubMed)

Other Identifiers

5R01AG027435-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0159

Identifier Type: -

Identifier Source: org_study_id