Can reduced dopamine availability and disrupted functional brain connectome serve as biomarkers for cognitive decline in aging?

Cognitive impairments impede the functioning of older people and create major individual and societal costs. Developing ways to preserve functioning in old age is thus of great importance.

However, knowledge about brain mechanisms that underlie cognitive decline is insufficient to enable effective intervention programs.

Changes in functional neural connectivity—the cross-talk between distant brain regions that collectively constitutes the human connectome—measured by functional MRI across different mental states, may be a potential mechanism underlying cognitive decline in aging. However, evidence relating age-related cognitive impairment to disruptions in functional connectome is sparse.

In addition, the molecular underpinnings of age-related alterations in functional connectome are largely unknown.

This stems from a lack of comprehensive integration of age-related changes in neurotransmitters measured by different dopaminergic markers (D1- and D2-like receptors), in relation to changes in connectome and cognitive deficits.

Due to this omission, many scientific questions remain inconclusive: To what extent do age-related neurochemical deficits cause functional alterations?

Do dopaminergic deficits and concomitant disruptive alterations in connectome mediate cognitive decline in aging, and how do these changes interrelate?

Answering such questions will pave the road for design and implementation of novel intervention programs that improve cognitive abilities in older age.