PMID- 38331332
OWN - NLM
STAT- MEDLINE
DCOM- 20240223
LR  - 20240223
IS  - 1095-9572 (Electronic)
IS  - 1053-8119 (Linking)
VI  - 288
DP  - 2024 Mar
TI  - Reduced default mode network effective connectivity in healthy aging is modulated 
      by years of education.
PG  - 120532
LID - S1053-8119(24)00027-2 [pii]
LID - 10.1016/j.neuroimage.2024.120532 [doi]
AB  - Aging is a major risk factor for neurodegenerative diseases like dementia and 
      Alzheimer's disease. Even in non-pathological aging, decline in cognitive 
      functioning is observed in the majority of the elderly population, necessitating 
      the importance of studying the processes involved in healthy aging in order to 
      identify brain biomarkers that promote the conservation of functioning. The 
      default mode network (DMN) has been of special interest to aging research due to 
      its vulnerability to atrophy and functional decline over the course of aging. 
      Prior work has focused almost exclusively on functional (i.e. undirected) 
      connectivity, yet converging findings are scarce. Therefore, we set out to use 
      spectral dynamic causal modeling to investigate changes in the effective (i.e. 
      directed) connectivity within the DMN and to discover changes in information flow 
      in a sample of cognitively normal adults spanning from 48 to 89 years (n = 63). 
      Age was associated to reduced verbal memory performance. Modeling of effective 
      connectivity revealed a pattern of age-related downregulation of posterior DMN 
      regions driven by inhibitory connections from the hippocampus and middle temporal 
      gyrus. Additionally, there was an observed decline in the hippocampus' 
      susceptibility to network inputs with age, effectively disconnecting itself from 
      other regions. The estimated effective connectivity parameters were robust and 
      able to predict the age in out of sample estimates in a leave-one-out 
      cross-validation. Attained education moderated the effects of aging, largely 
      reversing the observed pattern of inhibitory connectivity. Thus, medial 
      prefrontal cortex, hippocampus and posterior DMN regions formed an excitatory 
      cycle of extrinsic connections related to the interaction of age and education. 
      This suggests a compensatory role of years of education in effective 
      connectivity, stressing a possible target for interventions. Our findings suggest 
      a connection to the concept of cognitive reserve, which attributes a protective 
      effect of educational level on cognitive decline in aging (Stern, 2009).
CI  - Copyright (c) 2024. Published by Elsevier Inc.
FAU - Stoffel, Tibor
AU  - Stoffel T
AD  - Department of Social Psychology and Quantitative Psychology, Faculty of 
      Psychology, Universitat de Barcelona, Barcelona 08035, Spain; Department of 
      Nutritional Sciences, Faculty of Life Sciences, University of Vienna, 
      Josef-Holaubek-Platz 2 (UZA II), Vienna 1090, Austria. Electronic address: 
      tibor.stoeffel@univie.ac.at.
FAU - Vaque-Alcazar, Lidia
AU  - Vaque-Alcazar L
AD  - Department of Medicine, Faculty of Medicine and Health Sciences, Universitat de 
      Barcelona, Barcelona 08036, Spain; Institute of Biomedical Research August Pi i 
      Sunyer (IDIBAPS), Barcelona 08036, Spain.
FAU - Bartres-Faz, David
AU  - Bartres-Faz D
AD  - Department of Medicine, Faculty of Medicine and Health Sciences, Universitat de 
      Barcelona, Barcelona 08036, Spain; Institute of Biomedical Research August Pi i 
      Sunyer (IDIBAPS), Barcelona 08036, Spain.
FAU - Pero-Cebollero, Maribel
AU  - Pero-Cebollero M
AD  - Department of Social Psychology and Quantitative Psychology, Faculty of 
      Psychology, Universitat de Barcelona, Barcelona 08035, Spain; UB Institute of 
      Complex Systems, Universitat de Barcelona, Barcelona 08028, Spain; Institute of 
      Neurosciences, Universitat de Barcelona, Barcelona 08035, Spain.
FAU - Canete-Masse, Cristina
AU  - Canete-Masse C
AD  - Department of Social Psychology and Quantitative Psychology, Faculty of 
      Psychology, Universitat de Barcelona, Barcelona 08035, Spain; Institute of 
      Neurosciences, Universitat de Barcelona, Barcelona 08035, Spain.
FAU - Guardia-Olmos, Joan
AU  - Guardia-Olmos J
AD  - Department of Social Psychology and Quantitative Psychology, Faculty of 
      Psychology, Universitat de Barcelona, Barcelona 08035, Spain; UB Institute of 
      Complex Systems, Universitat de Barcelona, Barcelona 08028, Spain; Institute of 
      Neurosciences, Universitat de Barcelona, Barcelona 08035, Spain.
LA  - eng
PT  - Journal Article
DEP - 20240207
PL  - United States
TA  - Neuroimage
JT  - NeuroImage
JID - 9215515
SB  - IM
MH  - Adult
MH  - Humans
MH  - Aged
MH  - *Healthy Aging
MH  - Default Mode Network
MH  - Magnetic Resonance Imaging
MH  - Aging/physiology
MH  - Brain/pathology
MH  - Educational Status
OTO - NOTNLM
OT  - Cognitive reserve
OT  - Default mode network
OT  - Dynamic causal modeling
OT  - Education
OT  - Effective connectivity
OT  - Healthy aging
COIS- Declaration of competing interest None.
EDAT- 2024/02/09 00:42
MHDA- 2024/02/23 06:43
CRDT- 2024/02/08 19:19
PHST- 2023/10/18 00:00 [received]
PHST- 2024/01/20 00:00 [revised]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/02/23 06:43 [medline]
PHST- 2024/02/09 00:42 [pubmed]
PHST- 2024/02/08 19:19 [entrez]
AID - S1053-8119(24)00027-2 [pii]
AID - 10.1016/j.neuroimage.2024.120532 [doi]
PST - ppublish
SO  - Neuroimage. 2024 Mar;288:120532. doi: 10.1016/j.neuroimage.2024.120532. Epub 2024 
      Feb 7.