Clinical trial NCT00902499: Evolution of Memory Related Activity
Official title: Evolution of Memory-related fMRI Activation Over the Course of MCI and AD
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Alzheimer's Disease
Mild Cognitive Impairment
Keywords: functional magnetic resonance imaging
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
First posted: 2009-05-15
Enrollment: 160
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Memory Disorders Unit at Brigham and Women's Hospital, the Gerontology Research Unit at Massachusetts General Hospital, Alzheimer's Association, area physicians, and community dwelling adults

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital
name: Reisa Sperling, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.