Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia

Whiteside, David; Malpetti, Maura; Jones, P Simon; Ghosh, Boyd; Coyle‐Gilchrist, Ian; Swieten, John C. van; Seelaar, Harro; Jiskoot, Lize C.; Borroni, Barbara; Castilla, Joaquı́n; Moreno, Fermín; Laforce, Robert; Graff, Caroline; Synofzik, Matthis; Galimberti, Daniela; Masellis, Mario; Tartaglia, Maria Carmela; Finger, Elizabeth; Vandenberghe, Rik; Mendonça, Alexandre de; Tagliavini, Fabrizio; Butler, Chris; Santana, Isabel; Ber, Isabelle Le; Gerhard, Alexander; Ducharme, Simon; Levin, Johannes; Danek, Adrian; Otto, Markus; Sorbi, Sandro; Pasquier, Florence; Bouzigues, Arabella; Russell, Lucy L.; Rohrer, Jonathan D.; Rowe, James B.; Rittman, Timothy

doi:10.1002/alz.12824

Cited by 3 publications

(4 citation statements)

References 63 publications

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“…Maintenance of cognitive functions in genetic mutation carriers depends more on functional network integrity. This is consistent with findings from recent studies highlighting the link between functional networks and cognition in pre-symptomatic FTD [4,10]. The performance related to attention, processing speed and executive functions was correlated with global GMV in non-carriers, while correlated with left frontoparietal network integrity in pre-symptomatic carriers especially as they get older.…”

Section: Discussionsupporting

confidence: 92%

“…However, functional network organization and connectivity are generally maintained despite significant atrophy in pre-symptomatic genetic FTD [4, 9]. Moreover, a recent study indicates that functional networks predict cognitive decline and symptomatic conversion in pre-symptomatic genetic mutation carriers [10]. A better understanding of these changes in the pre-symptomatic stage would inform accurate staging, facilitate clinical trials, and elucidate the mechanisms of resilience by which gene carriers remain cognitively well for many years despite biomarker evidence of neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

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Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion

Liu,

Jones,

Pasternak

et al. 2024

Preprint

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INTRODUCTION: Gene carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion and functional patterns in pre-symptomatic stage could inform accurate staging and potential mechanisms. METHODS: We included 207 pre-symptomatic carriers and 188 relatives without mutations. The grey matter volume, cerebral perfusion, and resting-state functional network maps were co-analyzed using linked independent component analysis (LICA). Multiple regression analysis was used to investigate the relationship of LICA components to genetic status and cognition. RESULTS: Pre-symptomatic carriers showed an age-related decrease in the left frontoparietal network integrity while non-carriers did not. Executive functions of pre-symptomatic carriers dissociated from the level of atrophy and cerebrovascular dysfunction, but became dependent on the left frontoparietal network integrity in older age. DISCUSSION: The frontoparietal network integrity of pre-symptomatic carriers showed a distinctive relationship to age and cognition compared to non-carriers, despite atrophy and hypoperfusion. Functional network integrity may contribute to brain resilience in pre-symptomatic frontotemporal dementia, mitigating the effects of atrophy and hypoperfusion.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion

Liu,

Jones,

Pasternak

et al. 2024

Preprint

Self Cite

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“…The HMM‐multivariate autoregressive model (HMM‐MAR, https://github.com/OHBA-analysis/HMM-MAR) toolbox was applied to compute the HMM parameters. Three key metrics characterize the temporal dynamics of HMM states: fractional occupancy (FO), mean dwell time of HMM (MDTH), and switching rate (SR) 34–36 …”

Section: Methodsmentioning

confidence: 99%

“…Three key metrics characterize the temporal dynamics of HMM states: fractional occupancy (FO), mean dwell time of HMM (MDTH), and switching rate (SR). [34][35][36]…”

Section: Verification Analysis Of Network Measuresmentioning

confidence: 99%

Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea

Li,

Long,

Liu

et al. 2024

CNS Neurosci Ther

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PurposeTo investigate dynamic functional connectivity (dFC) within the cerebellar‐whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients.MethodsSixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum‐whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed.ResultsTwo dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep.ConclusionAbnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high‐order and low‐level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.

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Frontoparietal network integrity supports cognitive function in pre‐symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion

Liu,

Jones,

Pasternak

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONGenetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre‐symptomatic stage could inform accurate staging and potential mechanisms.METHODSWe included 207 pre‐symptomatic genetic mutation carriers and 188 relatives without mutations. The gray matter volume, cerebral perfusion, and resting‐state functional network maps were co‐analyzed using linked independent component analysis (LICA). Multiple regression analysis was used to investigate the relationship of LICA components to genetic status and cognition.RESULTSPre‐symptomatic mutation carriers showed an age‐related decrease in the left frontoparietal network integrity, while non‐carriers did not. Executive functions of mutation carriers became dependent on the left frontoparietal network integrity in older age.DISCUSSIONThe frontoparietal network integrity of pre‐symptomatic mutation carriers showed a distinctive relationship to age and cognition compared to non‐carriers, suggesting a contribution of the network integrity to brain resilience.Highlights A multimodal analysis of structure, perfusion, and functional networks. The frontoparietal network integrity decreases with age in pre‐symptomatic carriers only. Executive functions of pre‐symptomatic carriers dissociated from non‐carriers.

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Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia

Cited by 3 publications

References 63 publications

Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion

Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion

Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea

Frontoparietal network integrity supports cognitive function in pre‐symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion

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