Brain functional connectome across the human lifespan: links to white matter degeneration, dopamine depletion, and cognitive decline

PI: Alireza Salami, alireza.salami@ki.se

Cognitive impairments (problems with memory, thinking, and decision-making) impede the functioning of older people and create major individual and societal costs. Developing ways to preserve cognitive functioning in old age is thus of great importance. However, we do not yet know enough about the brain mechanisms that underlie cognitive decline to create effective intervention programs. Changes in functional neural connectivity—the cross-talk between distant brain regions that collectively constitutes the human connectome—may be a mechanism that underlies cognitive decline in aging. This is because, like cognitive decline in aging, age-related alterations in the functional connectome are heterogeneous. However, direct evidence relating age-related cognitive impairment to disruptions in the functional connectome is sparse.

The biological mechanisms underlying age-related alterations in functional connectome are largely unknown. This is because we have not yet comprehensively integrated information on age-related brain changes (e.g. the integrity of white matter and the density of specific dopamine receptors), changes in the connectome, and cognitive deficits. Due to this omission, many scientific questions remain: To what extent do age-related structural and neurochemical deficits in the brain cause functional alterations? Do structural disconnection, dopaminergic deficits, and concomitant disruptive alterations in the connectome mediate cognitive decline in aging, and if so, how do these changes interrelate?

In this novel study, we will answer these questions by integrating information on age-related cognitive decline and brain alterations measured by magnetic resonance imaging and positron emission tomography in 240 healthy adults aged between 25 and 80 years. The information produced by this study will pave the way for designing interventions that can successfully delay cognitive impairment in older people.

The project is funded by a grant from the Swedish Research Council.