Neurotransmitters are involved in memory aging in different ways  

Study investigates the role of noradrenaline and dopamine in memory loss  

Researchers at the Max Planck Institute for Human Development and the University of Southern California have succeeded in demonstrating that the neurotransmitters noradrenaline and dopamine are involved in age-related memory impairment in different ways. Their work contributes to a better understanding of cognitive aging with and without Alzheimer's dementia. 

One of the first signs of the possible later onset of Alzheimer's dementia is the accumulation of abnormal tau proteins in the brain, which can be detected from the age of around 30. Abnormal tau initially forms in small nuclei (cells clusters) in the brainstem that produce neurotransmitters, specifically dopamine and noradrenaline. These neurotransmitters ensure the stabilization of synaptic changes in memory-relevant areas of the brain and thus help us to retain memories permanently. With increasing age, abnormal tau proteins spread from these brain nuclei to memory-relevant brain areas and the dopamine- and noradrenaline-producing cells die off. This in turn leads to age-related cognitive impairment. However, it is unclear whether these two neurotransmitters play a different role in age-related cognitive changes. 

Researchers at the Max Planck Institute for Human Development and the University of Southern California used magnetic resonance imaging (MRI) in older adults to show that changes in brain regions that primarily produce noradrenaline were linked to episodic memory. This means that they influence the ability to store events and remember them over longer periods of time. In contrast, changes in regions primarily producing dopamine were linked to working memory, i.e., the ability to process and retain information for shorter periods of time. The results of their study were recently published in the journal Nature Aging. 

"The aim of our study was to expand our knowledge of the respective roles of dopaminergic and noradrenergic nuclei in memory loss in old age, as these regions are involved in the development of Alzheimer's dementia," says study leader Martin Dahl. He and his research group at the Center for Lifespan Psychology at the Max Planck Institute for Human Development are dedicated to investigating the so-called blue spot (locus coeruleus)—a small group of cells deep in the brain that is involved in the formation of these neurotransmitters (see interview). 

The researchers drew on data from the Berlin Aging Study II (BASE-II) – an ongoing longitudinal study investigating the neuronal, cognitive, physical, and social conditions of successful aging. They evaluated the MRI images of 69 younger participants aged 25 to 40 years and 251 older participants aged 62 to 83 years. In addition, the researchers used the results of cognitive assessments that were collected at several timepoints and allow statements to be made about changes of working and episodic memory as well as intelligence over time.    

"In the present study, we used new imaging techniques to decipher the role of declining dopaminergic and noradrenergic neurotransmitters on aging cognition. We repeatedly assessed cognitive performance and performed high-resolution MRI scans on large samples of younger and older adults over multiple time points," says co-author Mara Mather, professor of gerontology, psychology, and biomedical engineering at the University of Southern California. 

The researchers have recently received funding from the BrightFocus Foundation for a follow-up study in which they will investigate changes in these brain areas in relation to blood-based Alzheimer's biomarkers and their interaction in the development of Alzheimer's dementia.

Summary of the results:  

• Brain regions that produce certain neurotransmitters and are associated with the possible development of Alzheimer's disease examined using magnetic resonance imaging (MRI)  

• Age-associated changes in noradrenergic and dopaminergic neurotransmitter systems in around 300 participants of the Berlin Aging Study II (BASE-II) recorded over a period of around 2 years  

• Neurotransmitters differently involved in age-related memory impairment  

• Multimodal magnetic resonance imaging (MRI) examinations in combination with cognitive assessmentsMeasurement of different cognitive domains such as working memory, episodic memory, intelligence 

Original publications: