Altered structural network organization in cognitively normal individuals with amyloid pathology
Olga Voevodskaya, Joana B. Pereira, Giovanni Volpe, Olof Lindberg, Erik Stomrud, Danielle van Westen, Eric Westman & Oskar Hansson
Neurobiology of Aging 64, 15—24 (2018)
Recent findings show that structural network topology is disrupted in Alzheimer’s disease (AD), with changes occurring already at the prodromal disease stages. Amyloid accumulation, a hallmark of AD, begins several decades before symptom onset, and its effects on brain connectivity at the earliest disease stages are not fully known. We studied global and local network changes in a large cohort of cognitively healthy individuals (N = 299, Swedish BioFINDER study) with and without amyloid-β (Aβ) pathology (based on cerebrospinal fluid Aβ42/Aβ40 levels). Structural correlation matrices were constructed based on magnetic resonance imaging cortical thickness data. Despite the fact that no significant regional cortical atrophy was found in the Aβ-positive group, this group exhibited an altered global network organization, including decreased global efficiency and modularity. At the local level, Aβ-positive individuals displayed fewer and more disorganized modules as well as a loss of hubs. Our findings suggest that changes in network topology occur already at the presymptomatic (preclinical) stage of AD and may precede detectable cortical thinning.
Abnormal structural brain connectome in individuals with preclinical Alzheimer’s disease
Joana B. Pereira, Danielle van Westen, Erik Stomrud, Tor Olof Strandberg, Giovanni Volpe, Eric Westman & Oskar Hansson
Cerebral Cortex 28(10), 3638—3649 (2018)
Alzheimer’s disease has a long preclinical phase during which amyloid pathology and neurodegeneration accumulate in the brain without producing overt cognitive deficits. It is currently unclear whether these early disease stages are associated with a progressive disruption in the communication between brain regions that subsequently leads to cognitive decline and dementia. In this study we assessed the organization of structural networks in cognitively normal (CN) individuals harboring amyloid pathology (A+N−), neurodegeneration (A−N+), or both (A+N+) from the prospective and longitudinal Swedish BioFINDER study. We combined graph theory with diffusion tensor imaging to investigate integration, segregation, and centrality measures in the brain connectome in the previous groups. At baseline, our findings revealed a disrupted network topology characterized by longer paths, lower efficiency, increased clustering and modularity in CN A−N+ and CN A+N+, but not in CN A+N−. After 2 years, CN A+N+ showed significant abnormalities in all global network measures, whereas CN A−N+ only showed abnormalities in the global efficiency. Network connectivity and organization were associated with memory in CN A+N+ individuals. Altogether, our findings suggest that amyloid pathology is not sufficient to disrupt structural network topology, whereas neurodegeneration is.