In late life, lower LC neural density is associated with cognitive decline.

Because of the long unmyelinated axons of its neurons, high exposure to blood flow, and location adjacent to the 4th ventricle, the LC is especially vulnerable to toxins.

The tau pathology precursor of Alzheimer's disease emerges in the LC by early adulthood in most people. However, the pathology typically spreads slowly, and only some end up with clinically evident Alzheimer's disease.

Norepinephrine helps to protect neurons from factors that accelerate Alzheimer's disease, such as inflammation and excitotoxicity.

Education and engaging careers produce late-life ‘cognitive reserve’ or effective brain performance despite encroaching pathology. Activation of the LC–NE system by novelty and mental challenge throughout life may contribute to cognitive reserve.