PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)

Abstract: This protocol continues and expands a longitudinal brain positron emission tomography (PET) imaging study that will support multiple hypothesis-driven investigations within the Baltimore Longitudinal Study of Aging (BLSA). We are examining changes in brain structure, function, and neuropathology as predictors of cognitive decline and impairment through longitudinal neuroimaging assessments of selected 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 temporal and parietal cortex, will predict which individuals subsequently develop cognitive impairment and Alzheimer s disease (AD). Between 2005 and 2022, we 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. Additionally, between 2016 and 2022, we performed serial PET with the radiotracer (18F) flortaucipir (Tauvid (TM)) to measure neurofibrillary tau tangle pathology in a subset of the BLSA participants who undergo amyloid PET imaging. Through the current protocol we are continuing longitudinal amyloid and tau 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 (Neuraceq (R)) to measure in vivo amyloid distribution in individuals aged 55 years and older. In addition, we will implement PET imaging of tau neurofibrillary tangles using \[18F\]florquinitau (Tauklarify (TM)) PET scans. In combination, PET imaging of amyloid and tau will provide in vivo imaging biomarkers of neuropathology. Such biomarkers have been implemented into research guidelines for definition of preclinical AD as well as incorporated into guidelines for diagnosis of mild cognitive impairment. 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 and tau 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 and tau 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 and tau pathology in non-demented men and women throughout adulthood? * What is the frequency and progression of brain amyloid and tau 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 and tau accumulation? * What factors modulate cognitive and brain aging and how do they impact the relation between amyloid and tau pathology and cognitive outcomes? * How well do blood-based biomarkers of AD, collected through the main BLSA study, reflect amyloid and tau pathology in the brain?