UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Ewers M, Luan Y, Frontzkowski L, Neitzel J, Rubinski A, Dichgans M, Hassenstab J, Gordon BA, Chhatwal JP, Levin J, Schofield P, Benzinger TLS, Morris JC, Goate A, Karch CM, Fagan AM, McDade E, Allegri R, Berman S, Chui H, Cruchaga C, Farlow M, Graff-Radford N, Jucker M, Lee J-H, Martins RN, Mori H, Perrin R, Xiong C, Rossor M, Fox NC, O'Connor A, Salloway S, Danek A, Buerger K, Bateman RJ, Habeck C, Stern Y, Franzmeier N, Alzheimer’s Disease Neuroimaging Initiative and the Dominantly Inherited Alzheimer Network
  • Publication date:
    16/03/2021
  • Journal:
    Brain
  • Status:
    Published
  • Country:
    England
  • PII:
    6174116
  • Language:
    eng
  • Keywords:
    modularity, reserve, resilience, system segregation, tau-PET
Abstract
Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal aging, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state-fMRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: First, we included 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls. Second, we included 156 amyloid-PET positive subjects across the spectrum of sporadic Alzheimer's disease as well as 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal-lobe tau-PET (i.e. composite across Braak stage I & III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher fMRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (p = 0.007). Similarly, for sporadic Alzheimer's disease patients, higher fMRI-assessed system segregation was associated with less decrement in global cognition (p = 0.001) and episodic memory (p = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Neurodegenerative Diseases
Author
UCL Queen Square Institute of Neurology
Author
Neurodegenerative Diseases
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by