In a demographically diverse sample of healthy people, Cornell researchers found dramatic changes over the human lifespan in the brain’s “blue spot” – a tiny region involved in cognition and believed to be the first affected by neurodegenerative conditions including Alzheimer’s disease.

Using specialized MRI scans to measure the intensity of neuromelanin, a pigment that gives the locus coeruleus (LC) its blue color, the research team observed an inverted U-shaped curve that peaked in later middle age before dropping off sharply, a finding that helps characterize healthy aging patterns.

Maintaining a stronger blue signal after age 60 was associated with better cognitive performance, according to the study involving 134 participants aged 19 to 86. Because of the participants’ diversity, including about 40% who were non-white, the researchers also discovered higher peaks among Black participants and women, groups known to be more susceptible to Alzheimer’s.

“By examining the health of the locus coeruleus and its relation to cognitive aging processes, these data may reveal when an individual is on a healthy aging trajectory and advance our understanding of why certain groups may have higher incidence of Alzheimer’s disease later in life,” said Adam Anderson, professor in the Department of Psychology and the College of Human Ecology (CHE). “The results showed underlying similarities in LC risk markers across the lifespan, but areas of specific concern for distinct demographic groups, especially for some that have been underrepresented in medical research.”

The findings were reported in “Age-related Differences in Locus Coeruleus Intensity Across a Demographically Diverse Sample,” published March 17 in the journal Neurobiology of Aging. The Cornell team included Anderson and Eve De Rosa, the Mibs Martin Follett Associate Professor in Human Ecology (CHE) and dean of faculty, who co-lead the Affect and Cognition Lab (ACLAB); Khena Swallow, associate professor in the Department of Psychology and the College of Arts and Sciences; and ACLAB members Elizabeth Riley, a research associate and the paper’s first author; Nicholas Cicero ’20; and Senegal Mabry, a doctoral student in the field of neuroscience.

Located deep in the brainstem, the locus coeruleus is the primary source of norepinephrine, a neurotransmitter crucial for attention, memory, stress responses and even sleep. It is thought to be the brain region most vulnerable to Alzheimer’s pathology, potentially affected years or decades before symptoms show. Thus, a better understanding of normal and abnormal LC aging trajectories is considered crucial to earlier detection of such diseases.

Brain scans performed at the Cornell MRI Facility showed a consistent general pattern in healthy individuals’ LC signal intensity, regardless of education, income, and history of early trauma. Increased neuromelanin levels in midlife were associated with better cognition and decreases after age 60 with poorer cognitive performance. Ongoing research is exploring ways to help sustain healthy levels, potentially through practices such as deep breathing or stimulation of the vagus nerve.

Why the two subgroups showed more dramatic peaks in LC neuromelanin intensity is unclear, but the researchers said they are consistent with a theory of compensation: Overtaxing one’s brain and stressful living, which involves the LC, could be beneficial in the short term but deplete function later in life.

“While the locus coeruleus is required for alertness, focus and memory,” Anderson said, “heightened neuromelanin can also be a sign of overactivity and is implicated in depression, anxiety and post-traumatic stress disorder, all of which are risk factors for Alzheimer’s disease.”

The study’s racial and socioeconomic diversity – key to the findings’ overall generalizability and specific insights about subgroups – was achieved through a collaboration with the Community Recruitment Research Accelerator, a project of SUNY Upstate Medical University in Syracuse, New York. The project seeks to increase diverse community participation in brain health research, partnering with a community recruitment liaison to reduce barriers to participation.

“This study illustrates the importance of diverse samples in studying brain health,” Anderson said. “Diverse samples are necessary to generalize study results to the larger population, and a critical form of scientific validity.”

The research was supported by the National Institutes of Health.