Early Markers of Alzheimer Disease

National Institute On Aging

Investigators

Linked publications & trials

Abstract

The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The mission of the BLSA is to learn what happens to people as they get old and how to distinguish changes due to aging from those due to disease or other causes. The Early Markers of Alzheimer's Disease program continues to perform cognitive assessments and establish research diagnoses of Mild Cognitive Impairment and Alzheimer's Disease for BLSA participants. This information is used in multiple collaborative research projects conducted by intramural and extramural investigators, including our studies of brain aging and neuroimaging biomarkers of cognitive decline and AD. Over the last year, we have continued cognitive assessments of BLSA participants, as well as diagnostic case conferences to establish research diagnoses of cognitive impairment. We have continued to investigate possible modifiers of cognitive aging, risk for dementia, and the presence of Alzheimer's pathology at autopsy. In the last year, several studies integrating BLSA clinical and cognitive data with MRI and PET neuroimaging data have been published. These publications include demonstrations that elevated markers of inflammation are associated with longitudinal changes in regional cerebral blood flow measured by PET (Warren et al, 2018) and findings of accelerated rates of amyloid-beta accumulation in amyloid positive individuals who also have metabolic syndrome (Gomez et al, 2018). We have also used BLSA clinical and cognitive data to characterize the heterogeneity of structural and functional MR imaging patterns in individuals demonstrating advanced versus resilient aging (Eavani et al, 2018) and to determine associations between regional white matter lesions and clinical and cognitive characteristics (Habes et al, 2018). In addition, we continue to collaborate with investigators in the Translational Gerontology Branch, demonstrating that rate of muscle contraction is associated with cognition in women but not men (Tian et al, 2018). The Early Markers of Alzheimers Disease program continues to support the establishment of adjudicated diagnosis of cognitive impairment, including Alzheimers disease and related dementias. These diagnoses are used widely by intramural and extramural collaborators to determine cognitive status in a variety of studies, including to restrict study samples to cognitively normal individuals. Similarly BLSA autopsy material from the brain tissue bank is being used in conjunction with cognitive measures to characterize individuals who meet the diagnosis of primary age-related tauopathy (PART). We continue to collaborate extensively with both intramural and extramural investigators, including ongoing studies of motor function, sleep disturbance, hearing loss, and vision changes. Over the last year, we also have continued an active collaboration with a 5-study consortium of longitudinal studies focused on preclinical AD. Participants at the study sites are included in the consortium if they are cognitively normal at baseline, have either PET-PiB or cerebral spinal fluid measures of amyloid-beta and serial cognitive assessments. The collaboration and larger sample sizes provided by the 5 studies and the University of Pennsylvania image analysis core will allow tests of more complex interactions influencing risk and protective factors for Alzheimer's disease during preclinical asymptomatic stages.