TY - JOUR
T1 - Breakdown of specific functional brain networks in clinical variants of Alzheimer's disease
AU - Pini, Lorenzo
AU - Wennberg, Alexandra M.
AU - Salvalaggio, Alessandro
AU - Vallesi, Antonino
AU - Pievani, Michela
AU - Corbetta, Maurizio
N1 - Funding Information:
Maurizio Corbetta was supported by FLAG-ERA JTC 2017 (grant ANR-17-HBPR-0001 ); MIUR − Departments of Excellence Italian Ministry of Research ( MART_ECCELLENZA18_01 ); Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO) - Ricerca Scientifica di Eccellenza 2018 – (Grant Agreement number 55403 ); Ministry of Health Italy; Brain connectivity measured with high-density electroencephalography: a novel neurodiagnostic tool for stroke - NEUROCONN ( RF-2008−12366899 ); Celeghin Foundation Padova ( CUP C94I20000420007 ); BIAL Foundation grant (No. 361/18 ); H2020 European School of Network Neuroscience - euSNN, H2020-SC5–2019-2, (Grant Agreement number 869505 ); H2020 Visionary Nature Based Actions For Heath, Wellbeing & Resilience in Cities (VARCITIES), H2020-SC5–2019-2 (Grant Agreement number 869505 ); Ministry of Health Italy : Eye-movement dynamics during free viewing as biomarker for assessment of visuospatial functions and for closed-loop rehabilitation in stroke – EYEMOVINSTROKE ( RF-2019–12369300 ); Michela Pievani has received funding from the Italian Ministry of Health (Giovani Ricercatori grant GR2011–02349787 , Ricerca Corrente).
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/12
Y1 - 2021/12
N2 - Alzheimer's disease (AD) is characterized by different clinical entities. Although AD phenotypes share a common molecular substrate (i.e., amyloid beta and tau accumulation), several clinicopathological differences exist. Brain functional networks might provide a macro-scale scaffolding to explain this heterogeneity. In this review, we summarize the evidence linking different large-scale functional network abnormalities to distinct AD phenotypes. Specifically, executive deficits in early-onset AD link with the dysfunction of networks that support sustained attention and executive functions. Posterior cortical atrophy relates to the breakdown of visual and dorsal attentional circuits, while the primary progressive aphasia variant of AD may be associated with the dysfunction of the left-lateralized language network. Additionally, network abnormalities might provide in vivo signatures for distinguishing proteinopathies that mimic AD, such as TAR DNA binding protein 43 related pathologies. These network differences vis-a-vis clinical syndromes are more evident in the earliest stage of AD. Finally, we discuss how these findings might pave the way for new tailored interventions targeting the most vulnerable brain circuit at the optimal time window to maximize clinical benefits.
AB - Alzheimer's disease (AD) is characterized by different clinical entities. Although AD phenotypes share a common molecular substrate (i.e., amyloid beta and tau accumulation), several clinicopathological differences exist. Brain functional networks might provide a macro-scale scaffolding to explain this heterogeneity. In this review, we summarize the evidence linking different large-scale functional network abnormalities to distinct AD phenotypes. Specifically, executive deficits in early-onset AD link with the dysfunction of networks that support sustained attention and executive functions. Posterior cortical atrophy relates to the breakdown of visual and dorsal attentional circuits, while the primary progressive aphasia variant of AD may be associated with the dysfunction of the left-lateralized language network. Additionally, network abnormalities might provide in vivo signatures for distinguishing proteinopathies that mimic AD, such as TAR DNA binding protein 43 related pathologies. These network differences vis-a-vis clinical syndromes are more evident in the earliest stage of AD. Finally, we discuss how these findings might pave the way for new tailored interventions targeting the most vulnerable brain circuit at the optimal time window to maximize clinical benefits.
KW - Alzheimer's disease
KW - Early-onset
KW - Functional connectivity in atypical AD
KW - Language
KW - Network-symptoms coupling
KW - Posterior cortical atrophy
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U2 - 10.1016/j.arr.2021.101482
DO - 10.1016/j.arr.2021.101482
M3 - Review article
AN - SCOPUS:85116600677
VL - 72
JO - Ageing Research Reviews
JF - Ageing Research Reviews
SN - 1568-1637
M1 - 101482
ER -