Biomarker Exploration in Aging, Cognition and Neurodegeneration

The purpose of this research study is to understand the factors that underlie changes in thinking and memory with increasing age. The investigators will test the usefulness of MRI, PET, and cognitive testing in detecting subtle changes in the brain that precede cognitive decline. An addendum to this study includes additional PET scans to examine the relationship between tau protein in the brain and cognitive decline. Tau is a protein that is known to form tangles in the areas of the brain important for memory, and these tau tangles are a hallmark of Alzheimer's disease. This sub-study research aims to look at the tau accumulation in the brain using an investigational drug called MK-6240, which is a radio tracer that gets injected prior to a positron emission tomography (PET) scan.

This study investigates the relationship between Alzheimer's disease (AD) pathology, brain structure and function, as well as cognition in non-demented older adults. The goal is to develop a more complete understanding of the factors that lead to cognitive decline in the elderly and progression to AD. The investigators will enroll 200 cognitively intact adults between the ages of 60-85 years old from the UCI Alzheimer's Disease Research Center or directly from the local community. Study procedures will include: 1) PET amyloid scans with Amyvid™ radiotracer (florbetapir-F18) and PET tau scans with \[18F\]MK6240 radiotracer; 2) High-resolution structural, functional, and diffusion MRI; and 3) Cognitive examinations. The investigators will track cognitive outcomes through longitudinal monitoring. Amyloid imaging will only be conducted once in the study at baseline, and MRI and tau PET imaging will be at baseline and Year 1. The investigators aim to identify the best combination of tests for predicting longitudinal cognitive/clinical decline. The proposed study will significantly inform the understanding of cognitive decline in the aging brain and allow investigators to better define preclinical AD and make recommendations for future intervention trials.

Eligibility Criteria:
Inclusion Criteria:

1. Aged 60 or older;
2. Speaks fluent English or Spanish;
3. Visual and auditory acuity adequate for neuropsychological and computerized testing;
4. Good general health with no disease(s) expected to interfere with the study;
5. Willing and able to participate for the duration of the study and in all study procedures including MRI and PET;
6. Normal cognition defined as a Clinical Dementia Rating of 0 and a Mini-Mental State Examination score of 25 or higher. FAST Stage 1 or 2.
7. Subjective memory or other cognitive complaints will be included.

Exclusion Criteria:

1. Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm;
2. Major health conditions, except for Type II diabetes mellitus, hypercholesterolemia, and hypertension, which are NOT exclusionary for this study given their high prevalence in our target populations;
3. Significant psychiatric disorders such as schizophrenia, bipolar disorder, or attention-deficit hyperactivity disorder, except for depression and anxiety, which are NOT exclusionary for this study given their high prevalence in our target populations;
4. Existing diagnosis of dementia or mild cognitive impairment;
5. Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria);
6. MRI contraindications, e.g. pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body. Females who are pregnant or trying to get pregnant are also excluded;
7. PET contraindications, e.g. significant prior radiation exposure and pregnancy.