Amyloid PET Imaging in the Baltimore Longitudinal Study of Aging

Abstract

We are examining changes in brain structure, function, and neuropathology as predictors of cognitive decline and impairment through longitudinal neuroimaging assessments of selected Baltimore Longitudinal Study of Aging (BLSA) participants at the National Institute on Aging (NIA). The hypothesis driving this study is that accelerated preclinical changes in brain structure and function in specific regions, including mesial temporal cortex, cingulate cortex, precuneus, and inferior parietal cortex, will predict which individuals subsequently develop cognitive impairment and Alzheimer s disease. Since 2005, we have performed serial positron emission tomography (PET) with the radiotracer (11C) Pittsburgh compound B (PiB) to measure amyloid pathology in a subset of participants from the BLSA to investigate the neuropathological basis of memory change and cognitive impairment. Through the protocol we are continuing longitudinal amyloid PET imaging of older participants and evaluating new participants. In conjunction with each BLSA visit, we will perform a single PET scan of (18F) florbetaben (trade name Neuraceq TM) to measure in vivo amyloid distribution in individuals aged 55 years and older. Approximately half of the neuroimaging study participants are enrolled in the BLSA autopsy program, and the integration of autopsy and imaging findings is an active area of investigation to gain a better understanding of factors that promote cognitive resilience in individuals who have amyloid pathology but do not show memory impairment. In addition, we are using neuroimaging tools to investigate modulators of cognitive and brain changes, including sex differences in brain aging, genetic risk factors, and the effects of sex steroid and other hormones. An understanding of these brain-behavior associations and early detection of accelerated brain changes that predict cognitive decline and impairment will be critical in identifying individuals likely to benefit from new interventions.

Objectives:

The principal goal of the project is the acquisition of longitudinal data on regional brain amyloid levels in BLSA participants to investigate these changes in relation to other medical, brain imaging, psychological, and cognitive data collected through the BLSA. Specifically, the primary objectives are to continue to address the following questions:

• What are the rates and regional distribution of changes in brain amyloid pathology in nondemented men and women throughout adulthood?
• What is the frequency and progression of brain amyloid pathology in older adults and what is the clinical significance of these findings for cognitive aging?
• Against a background of age-related changes in brain structure and function, which changes predict cognitive impairment and dementia and when do these changes occur in relation to the onset of amyloid accumulation?
• What factors modulate cognitive and brain aging and how do they impact the relation between amyloid pathology and cognitive outcomes?
• How well do blood-based biomarkers of Alzheimer s disease, collected through the main BLSA study, reflect amyloid pathology in the brain?

• INCLUSION/EXCLUSION CRITERIA:
• Participants are men and women 55 years and older drawn from the BLSA sample and thus, represent the gender/ethnic characteristics of this study group. Enrollment is defined as the initial imaging session of the planned longitudinal study.
• Inclusion criteria: BLSA participants who do not meet exclusion criteria and have had or agreed to have an MRI under the BLSA study.
• Participants who lack capacity to consent will not be enrolled in the study. If the participant loses capacity to consent over the course of follow-up they will be removed them from the study. Competency to consent is assessed as part of the BLSA visit and we will not include people who are not competent to provide consent.

Exclusion criteria

• Preexisting central nervous system diseases
• Weight over 300 lbs.
• Active metastatic cancer (except basal cell cancer)
• Implanted electronic hearing devices
• Breast Cancer with radiation treatment
• Lymphoma
• Pacemaker
• Brain tumor
• Shrapnel
• Schizophrenia
• Bipolar disorder
• Epilepsy
• Language barrier that makes it difficult to understand participant.
• Aneurisms greater than 3mm
• Aneurysm clips
• Parkinson s disease/PD medications
• Huntington s disease
• Severe Endocrinopathy- treated thyroid conditions ok; treated, controlled diabetes ok. (exclude HbA1c over 8 which is poorly controlled diabetes)
• Diagnosis of dementia or mild cognitive impairment
• Younger than 55 years of age
• Pregnancy
• Ineligible for MRI
• History of stroke or documented TIAs requiring hospitalization
• Known brain vascular malformations or adenomas
• History of significant radiation exposure
• Those with a Blessed score of 4 or more with the BLSA will be reviewed at a research diagnostic case conference to rule out dementia diagnoses prior to enrollment.