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).

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.

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

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