Grant: Project Grant

People living with substance use disorders (SUDs) have higher risk of developing dementia later in life. However, the mechanisms behind this link are poorly understood. Preliminary evidence suggests that substance use may make the body and brain age faster. A small brain region located near the base of the brain, called the midbrain, is involved in thinking abilities and may be particularly vulnerable to the effects of age and the effects of substance use. It is therefore possible that the health of this structure may partially explain the link between substance use and elevated risk for dementia. Since the midbrain is very well-characterized on the cellular and molecular level, demonstrating these links may allow us to develop more effective and personalized treatment and prevention strategies to reduce the risk of dementia and cognitive impairment in people with SUDs. To evaluate this hypothesis, we propose to study the association between aging across young and middle age (ages 18-60) and the health of the midbrain assessed through a brain imaging technique called neuromelanin-sensitive MRI in a large sample of people with SUDs and a comparison group without SUDs. In the same people, we will also assess the links among age, midbrain health, thinking abilities and blood measures associated with cell aging. We expect that people with SUDs will have signs of faster aging and will resemble older individuals without SUDs on measures of midbrain health. We also expect to identify which specific aspects of thinking abilities and cell aging may be most strongly related to midbrain health in those with SUDs. This may in turn direct us to developing specific interventions to help more effectively prevent cognitive decline in those with SUDs.