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@ARTICLE{Behrenbruch:285481,
      author       = {Behrenbruch, Niklas and Schwarck, Svenja and
                      Schumann-Werner, Beate and Molloy, Eóin N. and Garcia
                      Garcia, Berta and Hochkeppler, Anne and Fischer, Larissa and
                      Büchel, Anna-Therese and Incesoy, Enise I. and Bernal, Jose
                      and Vockert, Niklas and Müller, Patrick and Behnisch,
                      Gusalija and Morgado, Bárbara and Esselmann, Hermann and
                      Seidenbecher, Constanze I. and Schott, Björn H. and
                      Barthel, Henryk and Sabri, Osama and Wiltfang, Jens and
                      Kreissl, Michael C. and Düzel, Emrah and Maass, Anne},
      title        = {{A} physically and mentally active lifestyle relates to
                      younger brain and cognitive age},
      journal      = {GeroScience},
      volume       = {aop},
      issn         = {2509-2715},
      address      = {[Cham]},
      publisher    = {Springer International Publishing},
      reportid     = {DZNE-2026-00258},
      pages        = {na},
      year         = {2025},
      abstract     = {Resistance to age-related pathological changes (brain
                      maintenance), including Alzheimer’s disease,
                      cerebrovascular disease, and neurodegeneration may promote
                      cognitive resilience in aging. However, how lifestyle and
                      health profiles relate to successful cognitive and brain
                      aging remains poorly understood. In a novel, deeply
                      phenotyped cohort of 211 cognitively unimpaired older adults
                      (age = 71.0 ± 7.4 years, $46\%$ female), we
                      characterized principal components of lifestyle and health
                      using questionnaire, fitness, and blood data. We estimated
                      cognitive age gap (CAG) based on comprehensive
                      neuropsychological data and brain age gap (BAG) based on
                      brain-pathology markers, including plasma biomarkers of
                      Alzheimer’s pathology (pTau217 and Aβ1-42/Aβ1-40),
                      MRI-based measures of white matter hyperintensities,
                      perivascular spaces, and brain atrophy. Regression analyses
                      tested how the observed lifestyle-health profiles were
                      related to CAG and BAG. Seven principal components explained
                      $49\%$ of the variance in health and lifestyle. The second
                      component, characterized by a mentally and physically active
                      life and low cardiovascular risk, was associated with lower
                      CAG (β = − 0.66, p < 0.001) and BAG (β =
                      − 0.52, p = 0.003), reflecting a
                      younger-than-expected brain and cognitive age, respectively.
                      The association of an active lifestyle and lower CAG was
                      partially mediated by BAG. Higher CAG was also associated
                      with other lifestyle components characterized by low mental
                      stimulation. APOE-ε4 carriers exhibited higher BAG. In
                      conclusion, a lifestyle combining low cardiovascular risk,
                      high mental engagement throughout life and high physical
                      activity/fitness is jointly associated with
                      less-than-expected brain pathology and better-than-expected
                      cognitive performance, supporting its involvement in brain
                      maintenance and cognitive resilience to aging.},
      cin          = {AG Maaß / AG Düzel / AG Wiltfang / AG Fischer / Core MR
                      PET},
      ddc          = {610},
      cid          = {I:(DE-2719)1311001 / I:(DE-2719)5000006 /
                      I:(DE-2719)1410006 / I:(DE-2719)1410002 /
                      I:(DE-2719)1340016},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1007/s11357-025-01764-w},
      url          = {https://pub.dzne.de/record/285481},
}