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@INPROCEEDINGS{Behrenbruch:283097,
      author       = {Behrenbruch, Niklas and Schwarck, Svenja and
                      Schumann-Werner, Beate and Molloy, Eóin N. and Hochkeppler,
                      Anne and Buechel, Anna-Therese and Moyano, Jose Bernal and
                      Incesoy, Enise I and Garcia-Garcia, Berta and Vockert,
                      Niklas and Marcos Morgado, Barbara and Fischer, Larissa and
                      Müller, Patrick and Behnisch, Gusalija and Seidenbecher,
                      Constanze I and Schott, Björn H and Esselmann, Hermann and
                      Wiltfang, Jens and Barthel, Henryk and Sabri, Osama and
                      Kreissl, Michael C and Düzel, Emrah and Maass, Anne},
      title        = {{L}ifestyle and health signatures of brain pathological and
                      cognitive aging},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {Suppl 8},
      issn         = {1552-5260},
      reportid     = {DZNE-2025-01504},
      pages        = {e109741},
      year         = {2025},
      abstract     = {While aging almost inevitably leads to some degree of
                      cognitive decline, the interindividual heterogeneity in the
                      trajectories of decline raises the question of the extent to
                      which resistance against pathology and cognitive resilience
                      are involved. Using a multimodal approach including
                      neuroimaging, fitness assessment, questionnaire data, and
                      Alzheimer's disease (AD) genetic risk and plasma biomarkers
                      (Figure 1), we aimed to characterize latent structures of
                      lifestyle, mental and bodily health, estimate indices of
                      brain (pathological) and cognitive aging, and relate
                      lifestyle/health profiles and AD genetic risk to these
                      indices.We analyzed a subsample of 211 cognitively normal
                      older adults aged ≥ 60 years from an ongoing study
                      (CRC1436) (age=71.0±7.4years, $46\%$ female). Using
                      principal component analysis, we derived seven principal
                      components (PCs) that capture latent structures of lifestyle
                      and general health from thirty variables (Figure 2B). To
                      characterize successful brain/cognitive aging, we calculated
                      a brain (BAG) and cognitive age gap (CAG) as the difference
                      between brain pathology-/cognition-predicted age and
                      chronological age (Figure 2A). Our novel BAG estimate
                      incorporated also AD pathology, white matter
                      hyperintensities and enlarged perivascular spaces. We
                      regressed the first seven principal components (PC) on BAG
                      and CAG to estimate the association of lifestyle/health
                      profiles with successful brain/cognitive aging. We further
                      assessed whether APOE4 carriers had higher BAG/CAG using a
                      two-sample t-test.We named the PCs according to their main
                      factor loadings (Figure 2B). PC1 (Low Mental Health), PC2
                      (Active Life), and PC5 (Mentally Inactive $\&$ Physically
                      Active) were significantly associated with CAG, whereas only
                      PC2 was significantly associated with BAG (Figure 3A). BAG
                      partly explained the relationship between PC2 and CAG
                      (partial mediation of $18.0\%$ of total effect, p = 0.027;
                      Figure 3B). Finally, APOE e4 carrier had significantly
                      higher BAG (p = 0.049), but not CAG (p = 0.155).Our results
                      suggest that factors of cognitive resilience and brain
                      maintenance are to some extent unified in an active
                      lifestyle described by physical fitness, mental leisure
                      activities, and lower cardiovascular risk. In addition,
                      engagement in mental leisure activities may explain
                      cognitive resilience independent of brain pathology.
                      Finally, genetic risk for AD may also accelerate brain aging
                      in cognitively healthy older adults.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Female / Aged / Male / Alzheimer Disease: genetics
                      / Alzheimer Disease: pathology / Alzheimer Disease:
                      diagnostic imaging / Brain: pathology / Brain: diagnostic
                      imaging / Middle Aged / Life Style / Magnetic Resonance
                      Imaging / Aging: pathology / Principal Component Analysis /
                      Aged, 80 and over / Neuroimaging / Biomarkers: blood /
                      Biomarkers (NLM Chemicals)},
      cin          = {AG Maaß / AG Düzel / AG Müller / AG Fischer / AG
                      Wiltfang / Core MR PET},
      ddc          = {610},
      cid          = {I:(DE-2719)1311001 / I:(DE-2719)5000006 /
                      I:(DE-2719)1310003 / I:(DE-2719)1410002 / I:(DE-2719)1410006
                      / I:(DE-2719)1340016},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      pubmed       = {pmid:41433525},
      pmc          = {pmc:PMC12724826},
      doi          = {10.1002/alz70862_109741},
      url          = {https://pub.dzne.de/record/283097},
}