The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 by Dr. Nathan Shock [1
]. The overall mission of the BLSA is to learn what happens to people as they get old and how to sort out changes due to aging from those due to disease or other causes. Initial enrollment in the study was limited to men but women have been included since 1978. A total of 3006 subjects have been enrolled over the years. Current enrollment is 1362 subjects of which 35% are women. The racial composition of the study is predominantly non-Hispanic white and the cohort is highly educated (the mean education is approximately 17 years).
The autopsy program of the BLSA, along with enhanced neurologic and cognitive evaluations, were initiated in 1986 through a collaboration between the Johns Hopkins University Alzheimer’s Disease Research Center (ADRC) and the Laboratory of Personality and Cognition at the National Institute on Aging (NIA). Since the inception of the autopsy program, there have been 238 deaths and 211 subjects have undergone autopsy, most of them including complete body autopsies with neuropathological evaluation and banking of fixed and frozen brain tissues. The mean age at death is 86.9 ± 8.2 years (range 57–102), and the mean interval between last evaluation and death is 8.7± 6.7 months.
The clinical pathological investigations of the BLSA focus on the morphological and biochemical changes that occur in normal aging, independent of clinical disease, as well as the early neuropathological changes of neurodegenerative diseases especially Alzheimer’s disease (AD). A guiding principle of these investigations is the notion that understanding changes occurring during the early-stage of a disease process is more likely to shed light on the underlying pathogenesis than studying end-stage pathological changes, which are likely to represent a final common pathway across different forms of cellular damage. In addition, we seek to identify biological processes that discriminate participants with mild underlying AD pathology who develop dementia from those who remain non-demented. Although AD is the most common neurodegenerative pathology in our cohort, it is often associated with other neurological conditions characterized by specific pathologies such as coexisting vascular lesions or Parkinson’s disease (PD). Moreover, there is strong evidence that age-associated brain neuropathological changes often represent the participation of the brain in multisystemic disorders and, therefore, information from brain autopsies is substantially more valuable when it is conducted in individuals who were clinically well characterized prior to death. The large proportion of complete autopsies in the BLSA makes the examination of these interactions possible.
The BLSA autopsy cohort is not fully representative of the population at large because it is predominantly male, white, and most subjects have college or graduate education and good access to medical care. Therefore, we believe all of these factors raise caveats for the interpretation of clinical and pathological findings in this cohort. Currently, the BLSA is enrolling females and minorities in an effort to allay some of the limitations cited above.