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@ARTICLE{NicolaisenSobesky:1048426,
      author       = {Nicolaisen-Sobesky, Eliana and Maleki Balajoo, Somayeh and
                      Mahdipour, Mostafa and Mihalik, Agoston and Olfati, Mahnaz
                      and Hoffstaedter, Felix and Mourao-Miranda, Janaina and
                      Tahmasian, Masoud and Eickhoff, Simon B. and Genon, Sarah},
      title        = {{C}ardiometabolic health and physical robustness map onto
                      distinct patterns of brain structure and neurotransmitter
                      systems},
      journal      = {PLoS biology},
      volume       = {23},
      number       = {11},
      issn         = {1544-9173},
      address      = {Lawrence, KS},
      publisher    = {PLoS},
      reportid     = {FZJ-2025-04637},
      pages        = {e3003498 -},
      year         = {2025},
      abstract     = {The link between brain health and risk/protective factors
                      for non-communicable diseases (such as high blood pressure,
                      high body mass index, diet, smoking, physical activity,
                      etc.) is increasingly acknowledged. However, the specific
                      effects that these factors have on brain health are still
                      poorly understood, delaying their implementation in
                      precision brain health. Here, we studied the multivariate
                      relationships between risk factors for non-communicable
                      diseases and brain structure, including cortical thickness
                      (CT) and gray matter volume (GMV). Furthermore, we adopted a
                      systems-level perspective to understand such relationships,
                      by characterizing the cortical patterns (yielded in
                      association to risk factors) with regards to brain
                      morphological and functional features, as well as with
                      neurotransmitter systems. Similarly, we related the pattern
                      of risk/protective factors dimensions with a peripheral
                      marker of inflammation. First, we identified latent
                      dimensions linking a broad set of risk factors for
                      non-communicable diseases to parcel-wise CT and GMV across
                      the whole cortex. Data was obtained from the UK Biobank (n =
                      7,370, age range = 46-81 years). We used regularized
                      canonical correlation analysis (RCCA) embedded in a machine
                      learning framework. This approach allows us to capture
                      inter-individual variability in a multivariate association
                      and to assess the generalizability of the model. The brain
                      patterns (captured in association with risk/protective
                      factors) were characterized from a multi-level perspective,
                      by performing correlations (spin tests) between them and
                      different brain patterns of structure, function, and
                      neurotransmitter systems. The association between the
                      risk/protective factors pattern and C-reactive protein (CRP,
                      a marker of inflammation) was examined using Spearman
                      correlation. We found two significant and partly replicable
                      latent dimensions. One latent dimension linked
                      cardiometabolic health to brain patterns of CT and GMV and
                      was consistent across sexes. The other latent dimension
                      linked physical robustness (including non-fat mass and
                      strength) to patterns of CT and GMV, with the association to
                      GMV being consistent across sexes and the association to CT
                      appearing only in men. The CT and GMV patterns of both
                      latent dimensions were associated to the binding potentials
                      of several neurotransmitter systems. Finally, the
                      cardiometabolic health dimension was correlated to CRP,
                      while physical robustness was only very weakly associated to
                      it. We observed robust, multi-level and multivariate links
                      between both cardiometabolic health and physical robustness
                      with respect to CT, GMV, and neurotransmitter systems.
                      Interestingly, we found that cardiometabolic health and
                      physical robustness are associated with not only increases
                      in CT or GMV, but also with decreases of CT or GMV in some
                      brain regions. Our results also suggested a role for
                      low-grade chronic inflammation in the association between
                      cardiometabolic health and brain structural health. These
                      findings support the relevance of adopting a holistic
                      perspective in health, by integrating neurocognitive and
                      physical health. Moreover, our findings contribute to the
                      challenge to the classical conceptualization of
                      neuropsychiatric and physical illnesses as categorical
                      entities. In this perspective, future studies should further
                      examine the effects of risk/protective factors on different
                      brain regions in order to deepen our understanding of the
                      clinical significance of such increased and decreased CT and
                      GMV.},
      cin          = {INM-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5251},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1371/journal.pbio.3003498},
      url          = {https://juser.fz-juelich.de/record/1048426},
}