My primary research interests lie in the study of exceptionally long-lived individuals and the ability of some to avoid or be more resilient to cognitive dysfunction to very old ages. Building on my research experience in running the day-to-day activities of 2 longitudinal studies of human longevity, the New England Centenarian Study (NECS) and the NIA-funded U-19 Boston Center of the Long Life Family Study (LLFS), my earliest research projects were focused on the compression of morbidity and disability among centenarians and long-lived families. Historically, gerontologists and the lay public assumed that living longer was associated with an increased duration of age-related illnesses. Then, in 1980, Jim Fries proposed his compression of morbidity hypothesis, suggesting that as people live to the limit of human life span, they necessarily postpone or delay age-related diseases towards the end of life. We first investigated this hypothesis in relation to cancer, normally associated with high mortality risk. In this study that I led and which according to Google Scholar has been cited by 64 other papers, we documented a 17-year delay in the onset of cancer diagnoses compared with a national cancer database. Much more recently, we published evidence that those truly near the limit of human life span, supercentenarians (age 110+ years), postpone not only morbidity but also functional and cognitive decline. The supercentenarians spend an average of the last 5 years of their lives with one or more age-related diseases whereas younger centenarians spend approximately 9 years with morbidity. This study has become a seminal paper in the field of exceptional longevity evidenced by the fact that it has been cited by 309 other papers. Together, these studies demonstrate that extremely long-lived individuals are models for disease-free aging that can help us learn more about health spans and successful aging.
For me, the most exciting areas of exceptional aging research are cognitive reserve and the maintenance of cognitive function into extreme old age. The ability of many long-lived individuals to avoid dementia sparked my interest in studying whether their family members have better cognition than their peers. I led an analysis of cognitive function among centenarian offspring in the New England Centenarian Study which revealed that they have a 46% lower odds of baseline cognitive impairment and were 35% less likely to become cognitively impaired over 8 years of follow up compared with referents without familial longevity. Similarly, in the Long Family Study, I was involved in studies revealing that family members from the offspring generation perform better on some tests of neuropsychological function than their spouses who do not have familial longevity. Assessment of more specific deficits in cognitive function consistent with Alzheimer’s disease revealed lower risk of impairment among individuals with familial longevity compared with their spouses. These findings led me to write a viewpoint article on the potential of centenarians to serve as models of resistance and resilience to Alzheimer’s disease which became the foundation of the multi-site U19 project called Resilience/Resistance to Alzheimer’s Disease in Centenarians and Offspring (RADCO). In addition to being a multiple PI of this project, I am the lead of the Phenotyping and Biospecimen Core, responsible for constructing and implementing protocols to identify cognitive “superagers” and comprehensively evaluating their brain function. I am also the lead investigator of Project 1 which aims to gauge levels of resilience to Alzheimer’s disease by integrating neuropsychological, blood biomarker, neuroimaging, and neuropathological data to understand whether the ability to avoid or cope better with pathological brain changes contributes to exceptional cognitive until the end of life.
My other primary area of research focuses on methods of detecting subclinical cognitive changes. As an expert in the area of neuropsychological assessment and analyses, I play a critical role in the development of neuropsychological testing protocols across our studies as well as the implementation of digital technologies to capture spoken language and motor function during test performance. On this novel forefront of digital neuropsychological assessment, I am currently involved in the development and analysis of digital markers of cognitive function. Using data collected with a digital pen on a test of psychomotor speed, I led research that showed patterns of change in performance speed that were related to specific physical and cognitive functions suggesting the ability to differentiate motor slowing versus cognitive slowing. Variations in written, as well as verbal, responses captured with digital technologies may prove to be sensitive, efficient, and objective markers of cognitive impairment beyond what can be captured by standard hand-scoring of test data. The hope is that these digital markers may be integrated into the technologies that we already use in our daily lives to capture changes in cognitive function as early as possible to prevent future decline.