Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Abstract

INTRODUCTION: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial Frontotemporal dementia (FTD). METHODS: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. RESULTS: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviourally-relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. DISCUSSION: Our findings suggest that maintenance of functional network connectivity enables carriers to maintain cognitive performance.

Investigating the Roles of Anterior Cingulate in Behavioral Variant Frontotemporal Dementia: A PET/MRI Study

“…Hypometabolism reflects genuine functional damage because glucose is vital for the brain to participate in various critical functions, such as adenosine triphosphate production, oxidative stress management, and synthesis of neurotransmitters, neuromodulators, and structural components [42]. Coupling between function network and cognition was found stronger in presymptomatic carriers, also provide evidence that the independent and synergistic effects exist in different image modalities [43]. Some patients with bvFTD primarily present with negative symptoms, which include apathy, inertia, and loss of volition, whereas other patients predominantly present with positive symptoms, such as impulsiveness, disinhibition, and hyperactivity [1,2,44].…”

The role of the arousal system in age‐related differences in cortical functional network architecture

“…We tested the multivariate association between ARAS‐association network connectivity and age‐related changes in cognitive performance given that maintaining cortical‐wide connectivity is increasingly important for performance in old age (Bethlehem et al, 2020; Tibon et al, 2021; Tsvetanov et al, 2016; Tsvetanov et al, 2021). Overall, higher levels of ARAS‐association network connectivity were associated with better levels of cognition.…”

“…For the connectivity‐behavior analysis, we adopted a two‐level approach (Passamonti et al, 2019; Tibon et al, 2021; Tsvetanov et al, 2016; 2021). In the first level, to determine which (if any) connections between the ARAS and cortex were important for cognitive performance, we ran a canonical correlation analysis (CCA; Sui, Adali, Yu, Chen, & Calhoun, 2012; Wang et al, 2020) to identify linear relationships between the two sets of measures (ARAS‐association network connectivity, and cognitive performance in our main cognitive variables of interest from Cam‐CAN).…”

“…Finally, we predicted that the multivariate relationship between ARAS‐association network connectivity and cognitive performance will vary with aging (Bethlehem et al, 2020; Tibon et al, 2021; Tsvetanov et al, 2016, 2021). Since the DMN, FPCN, DAN, and SN have primarily been implicated in memory and attentional control (e.g., Grady et al, 2016; Sala‐Llonch et al, 2015; Shaw et al, 2015; Siman‐Tov et al, 2017), we limited our analyses to tasks from the CamCAN that measure these cognitive functions (including ACE‐R, Cattell test of fluid intelligence, Story Recall, Choice Reaction Time, and Visual Short‐term Memory).…”

Separating vascular and neuronal effects of age on fMRI BOLD signals

“…Current models of neurovascular ageing [25,301] provide an array of biological pathways leading to global brain tissue loss/atrophy and cognitive deficits, mainly in agerelated neurodegeneration. However, such models are suboptimal for characterizing healthy and successful ageing, where cognitive function is maintained in the presence of brain atrophy [302]. In addition, the link between age-related changes in brain tissue and cognition is surprisingly weak, and it has proven difficult to establish region-by-region correlations between brain structure and cognitive function [303].…”