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Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia

Published on May 1, 2019in Neurobiology of Aging 4.40
· DOI :10.1016/j.neurobiolaging.2018.12.009
Timothy Rittman18
Estimated H-index: 18
(University of Cambridge),
Robin Borchert4
Estimated H-index: 4
(University of Cambridge)
+ 122 AuthorsMiren Zulaica1
Estimated H-index: 1
The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.
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  • Citations (1)
Published on Nov 1, 2018in Nature Reviews Neuroscience 33.16
Roberto Cabeza83
Estimated H-index: 83
(Duke University),
Marilyn Albert108
Estimated H-index: 108
(Johns Hopkins University)
+ 10 AuthorsPatricia A. Reuter-Lorenz53
Estimated H-index: 53
(UM: University of Michigan)
Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of t...
27 Citations Source Cite
Published on Sep 1, 2018in Alzheimers & Dementia 14.42
Yaakov Stern125
Estimated H-index: 125
(Columbia University),
Eider M. Arenaza-Urquijo17
Estimated H-index: 17
(Mayo Clinic)
+ 31 AuthorsGerd Kempermann80
Estimated H-index: 80
(German Center for Neurodegenerative Diseases)
Abstract Several concepts, which in the aggregate get might be used to account for "resilience" against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these construct...
24 Citations Source Cite
Published on Feb 1, 2018in Brain 11.81
Thomas E. Cope12
Estimated H-index: 12
(University of Cambridge),
Timothy Rittman18
Estimated H-index: 18
(University of Cambridge)
+ 8 AuthorsJohn T. O'Brien97
Estimated H-index: 97
(University of Cambridge)
NIHR, MRC, Wellcome, Patrick Berthoud Charitable Trust, Association of British Neurologists
29 Citations Source Cite
Published on Jun 1, 2017in Brain 11.81
Enrico Premi17
Estimated H-index: 17
(University of Brescia),
Mario Grassi29
Estimated H-index: 29
(UNIPV: University of Pavia)
+ 24 AuthorsRobert Laforce15
Estimated H-index: 15
(Laval University)
Frontotemporal dementia is a heterogeneous neurodegenerative disorder with around a third of cases having autosomal dominant inheritance. There is wide variability in phenotype even within affected families, raising questions about the determinants of the progression of disease and age at onset. It has been recently demonstrated that cognitive reserve, as measured by years of formal schooling, can counteract the ongoing pathological process. The TMEM106B genotype has also been found to be a modi...
12 Citations Source Cite
Published on Dec 1, 2016in Neurobiology of Aging 4.40
Timothy Rittman18
Estimated H-index: 18
(University of Cambridge),
Mikail Rubinov19
Estimated H-index: 19
(University of Cambridge)
+ 7 AuthorsJames B. Rowe53
Estimated H-index: 53
(University of Cambridge)
Abnormalities of tau protein are central to the pathogenesis of progressive supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences the risk of Parkinson disease and Parkinson's disease dementia. We assessed whether regional MAPT expression might be associated with selective vulnerability of global brain networks to neurodegenerative pathology. Using task-free functional magnetic resonance imaging in progressive supranuclear palsy, Parkinson disease, and healthy subjects ...
18 Citations Source Cite
Published on Nov 1, 2016in The Lancet 59.10
Yu-Tzu Wu14
Estimated H-index: 14
(University of Exeter),
Julia C. Teale2
Estimated H-index: 2
(University of Exeter)
+ 3 AuthorsLinda Clare53
Estimated H-index: 53
(University of Exeter)
Abstract Background A wide range of lifestyle factors has been related to cognitive decline and dementia but the mechanisms have not been investigated completely. Cognitive reserve, the ability to optimise or maximise cognitive performance by drawing on a range of brain networks and cognitive strategies, accumulates throughout the life course and might have a mediating role in the pathway between lifestyle factors and cognitive function in later life. The aim of this study was to investigate the...
2 Citations Source Cite
Published on Jun 1, 2016in Lancet Neurology 28.75
Bob Olsson4
Estimated H-index: 4
(University of Gothenburg),
Ronald Lautner7
Estimated H-index: 7
(University of Gothenburg)
+ 12 AuthorsGabrielle Strobel1
Estimated H-index: 1
Summary Background Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF an...
332 Citations Source Cite
Published on Mar 1, 2016in Human Brain Mapping 4.55
Zheng Xu Ye1
Estimated H-index: 1
(University of Cambridge),
Charlotte L. Rae11
Estimated H-index: 11
(University of Cambridge)
+ 13 AuthorsEllemarije Altena15
Estimated H-index: 15
(University of Cambridge)
Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with...
27 Citations Source Cite
Published on Jan 1, 2016in Brain Structure & Function 3.62
Maria A. Rocca71
Estimated H-index: 71
(UniSR: Vita-Salute San Raffaele University),
Paola Valsasina38
Estimated H-index: 38
(UniSR: Vita-Salute San Raffaele University)
+ 3 AuthorsMassimo Filippi115
Estimated H-index: 115
(UniSR: Vita-Salute San Raffaele University)
Aim of this study was to explore the topological organization of functional brain network connectivity in a large cohort of multiple sclerosis (MS) patients and to assess whether its disruption contributes to disease clinical manifestations. Graph theoretical analysis was applied to resting state fMRI data from 246 MS patients and 55 matched healthy controls (HC). Functional connectivity between 116 cortical and subcortical brain regions was estimated using a bivariate correlation analysis. Glob...
46 Citations Source Cite
Published on Jun 1, 2015in Human Brain Mapping 4.55
Kamen A. Tsvetanov9
Estimated H-index: 9
Richard N. A. Henson76
Estimated H-index: 76
(Cognition and Brain Sciences Unit)
+ 6 AuthorsJames B. Rowe53
Estimated H-index: 53
(Medical Research Council)
In functional magnetic resonance imaging (fMRI) research one is typically interested in neu- ral activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive function- ing with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been propo...
53 Citations Source Cite
Cited By1
Published on Jun 19, 2019in bioRxiv
Frank Hubert Hezemans (Cognition and Brain Sciences Unit), Noham Wolpe6
Estimated H-index: 6
(University of Cambridge),
James B. Rowe53
Estimated H-index: 53
(University of Cambridge)
Apathy is a debilitating syndrome that is associated with reduced goal-directed behaviour. Although apathy is common and detrimental to prognosis in many neuropsychiatric diseases, its underlying mechanisms remain controversial. We propose a new model of apathy, in the context of Bayesian theories of brain function, whereby actions require predictions of their outcomes to be held with sufficient precision for 9explaining away9 differences in sensory inputs. In this active inference model, apathy...
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