DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes: A new window into cognitive aging

• Published in: Journal of neuroscience research Vol. 100; no. 6; pp. 1296 - 1320
• Main Authors: Nordin, Kristin, Gorbach, Tetiana, Pedersen, Robin, Panes Lundmark, Vania, Johansson, Jarkko, Andersson, Micael, McNulty, Charlotte, Riklund, Katrine, Wåhlin, Anders, Papenberg, Goran, Kalpouzos, Grégoria, Bäckman, Lars, Salami, Alireza
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2022; John Wiley and Sons Inc
• Subjects: Adult; Age; Aging; Brain; Brain - diagnostic imaging; Brain - pathology; Brain architecture; Cognition; Cognition - physiology; Cognitive ability; Cognitive Aging; Connectome; Dopamine; Dopamine D1 receptors; Dopamine D2 receptors; Humans; Life span; lifespan; Longitudinal Studies; Magnetic Resonance Imaging; Medical imaging; Medicin och hälsovetenskap; Memory; Neural networks; Neuroimaging; Perfusion; PET; Positron emission; Positron emission tomography; Prospective Studies; Raclopride; Short term memory; Structure-function relationships; Substantia alba; Substantia grisea; Tomography; connectome; aging; cognition; dopamine; lifespan; PET
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.25039

Concomitant exploration of structural, functional, and neurochemical brain mechanisms underlying age‐related cognitive decline is crucial in promoting healthy aging. Here, we present the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5‐year longitudinal study spanning the adult human lifespan. DyNAMiC examines age‐related changes in the brain’s structural and functional connectome in relation to changes in dopamine D1 receptor availability (D1DR), and their associations to cognitive decline. Critically, due to the complete lack of longitudinal D1DR data, the true trajectory of one of the most age‐sensitive dopamine systems remains unknown. The first DyNAMiC wave included 180 healthy participants (20–80 years). Brain imaging included magnetic resonance imaging assessing brain structure (white matter, gray matter, iron), perfusion, and function (during rest and task), and positron emission tomography (PET) with the [11C]SCH23390 radioligand. A subsample (n = 20, >65 years) was additionally scanned with [11C]raclopride PET measuring D2DR. Age‐related variation was evident for multiple modalities, such as D1DR; D2DR, and performance across the domains of episodic memory, working memory, and perceptual speed. Initial analyses demonstrated an inverted u‐shaped association between D1DR and resting‐state functional connectivity across cortical network nodes, such that regions with intermediate D1DR levels showed the highest levels of nodal strength. Evident within each age group, this is the first observation of such an association across the adult lifespan, suggesting that emergent functional architecture depends on underlying D1DR systems. Taken together, DyNAMiC is the largest D1DR study worldwide, and will enable a comprehensive examination of brain mechanisms underlying age‐related cognitive decline. This study presents the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5‐year longitudinal study of the adult human lifespan. DyNAMiC examines age‐related differences in the brain’s structural and functional connectomes in relation to the dopaminergic (DA) D1 receptor system, and their associations to cognition in aging. Initial findings demonstrate an inverted u‐shaped effect of DA D1 receptor availability on functional connectivity across cortical network nodes.