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000283097 041__ $$aEnglish
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000283097 1001_ $$0P:(DE-2719)9002133$$aBehrenbruch, Niklas$$b0$$eFirst author
000283097 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada
000283097 245__ $$aLifestyle and health signatures of brain pathological and cognitive aging
000283097 260__ $$c2025
000283097 3367_ $$0PUB:(DE-HGF)1$$2PUB:(DE-HGF)$$aAbstract$$babstract$$mabstract$$s1767099192_6289
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000283097 520__ $$aWhile 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.
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000283097 650_7 $$2NLM Chemicals$$aBiomarkers
000283097 650_2 $$2MeSH$$aHumans
000283097 650_2 $$2MeSH$$aFemale
000283097 650_2 $$2MeSH$$aAged
000283097 650_2 $$2MeSH$$aMale
000283097 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000283097 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000283097 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000283097 650_2 $$2MeSH$$aBrain: pathology
000283097 650_2 $$2MeSH$$aBrain: diagnostic imaging
000283097 650_2 $$2MeSH$$aMiddle Aged
000283097 650_2 $$2MeSH$$aLife Style
000283097 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000283097 650_2 $$2MeSH$$aAging: pathology
000283097 650_2 $$2MeSH$$aPrincipal Component Analysis
000283097 650_2 $$2MeSH$$aAged, 80 and over
000283097 650_2 $$2MeSH$$aNeuroimaging
000283097 650_2 $$2MeSH$$aBiomarkers: blood
000283097 7001_ $$0P:(DE-2719)9000379$$aSchwarck, Svenja$$b1
000283097 7001_ $$0P:(DE-2719)9002320$$aSchumann-Werner, Beate$$b2
000283097 7001_ $$0P:(DE-2719)9002180$$aMolloy, Eóin N.$$b3
000283097 7001_ $$0P:(DE-2719)2812346$$aHochkeppler, Anne$$b4
000283097 7001_ $$0P:(DE-2719)9001800$$aBuechel, Anna-Therese$$b5
000283097 7001_ $$0P:(DE-2719)9001989$$aMoyano, Jose Bernal$$b6
000283097 7001_ $$0P:(DE-2719)9001517$$aIncesoy, Enise I$$b7
000283097 7001_ $$0P:(DE-2719)2812734$$aGarcia-Garcia, Berta$$b8
000283097 7001_ $$0P:(DE-2719)9000804$$aVockert, Niklas$$b9
000283097 7001_ $$0P:(DE-2719)9003591$$aMarcos Morgado, Barbara$$b10
000283097 7001_ $$0P:(DE-2719)9002356$$aFischer, Larissa$$b11
000283097 7001_ $$0P:(DE-2719)2811487$$aMüller, Patrick$$b12
000283097 7001_ $$0P:(DE-HGF)0$$aBehnisch, Gusalija$$b13
000283097 7001_ $$aSeidenbecher, Constanze I$$b14
000283097 7001_ $$0P:(DE-2719)2814326$$aSchott, Björn H$$b15
000283097 7001_ $$aEsselmann, Hermann$$b16
000283097 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b17
000283097 7001_ $$aBarthel, Henryk$$b18
000283097 7001_ $$0P:(DE-2719)2814810$$aSabri, Osama$$b19
000283097 7001_ $$0P:(DE-2719)2812799$$aKreissl, Michael C$$b20
000283097 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emrah$$b21
000283097 7001_ $$0P:(DE-2719)2811815$$aMaass, Anne$$b22$$eLast author
000283097 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70862_109741$$gVol. 21 Suppl 8, no. Suppl 8, p. e109741$$nSuppl 8$$pe109741$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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