Vascular dysfunction, neuroinflammation, and dopamine loss - a chain of events underlying cognitive decline in aging?

Cognitive decline and dementia compromise health for a great number of older individuals, and come with massive medical costs.

One of the most acknowledged theories in cognitive neuroscience is that the age-sensitivity of the dopamine system underlies cognitive decline in aging. Hence, circumventing dopamine loss may constitute one route towards successful cognitive aging. It is therefore crucial to identify the determinants of dopamine loss.

We hypothesize that a triad of cerebrovascular stress, neuroinflammation, and dopamine loss are an integral part of one pathological chain of events in the aging brain, leading to concomitant cognitive impairments.

To test this hypothesis, we will employ (i) multimodal brain imaging to map in vivo dopamine integrity, cerebrovascular functions, and neuroinflammation; (ii) epigenetic markers of peripheral inflammation, and (iii) detailed cognitive testing in two samples of healthy, older adults (240 in total, ages: 60-80-years, approx. 50% men).

A 5-year follow-up has been conducted in 129 individuals, allowing for longitudinal analyses of whether changes in these neurocognitive variables correlate in aging.

This project will generate new knowledge of cascades taking place along the path of compromised brain maintenance, which may serve as a foundation for future interceptive strategies.