ALZHEIMERS RESEARCH PROJECT: 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 age and how to distinguish changes due to aging from those due to disease or other causes. Technological advances increasingly allow us to examine subclinical disease markers in the brain and body more generally, blurring distinctions between aging-related and disease-related changes. Thus, longitudinal studies have assumed increasing importance in elucidating the earliest changes that may be associated with later symptomatic cognitive impairment. 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 and related dementias for BLSA participants. This information is also used in multiple collaborative research projects conducted by intramural and extramural investigators, including our LBN studies of brain aging and neuroimaging biomarkers of cognitive decline and AD (reported separately). Over the last several years, we have spearheaded assays of plasma biomarkers of AD pathology and neurodegeneration, utilizing historical samples stored as part of BLSA studies of physical and cognitive aging. These plasma biomarkers have been used in combination with cognitive and neuroimaging data to investigate the predictive utility of biomarkers of AD and neurodegeneration and in tracking longitudinal cognitive decline and brain atrophy (Dark et al., 2024). They have also been used to stratify participants by B-amyloid 42/40 ratio in studies of proteomic indicators of a variety of health conditions, including conditions related to prior infection. Clinical and neuropsychological data provided through the Early Markers of AD program have also enabled stratification of imaging and other studies by cognitive impairment status (Archer etal., 2024, Yang et al., 2024) and have allowed investigation of multi-sensory function in relation to early cognitive impairment (Cao et al., 2023), brain amyloid (Yesantharao et al., 2023) and brain atrophy (Tian et al. 2023). In a continuing collaboration with Drs.Tian and Ferrucci, we have continued investigation of individuals who show both memory and gait decline - "dual decliners" (Tian et al., 2023; 2024) and have begun to examine mitochondrial function measured in thigh muscle in relation to cognitive and brain measures (Tian et al., 2024). We have also continued active collaborations with the Johns Hopkins Neuropathology group (Chang et al., 2024) and the Preclinical AD Consortium a 5-study consortium of longitudinal studies focused on preclinical AD.