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@ARTICLE{Son:272148,
      author       = {Son, Hye Joo and Kim, Jae Seung and Bateman, Randall J and
                      Kim, Seonok and Llibre-Guerra, Jorge J and Day, Gregory S
                      and Chhatwal, Jasmeer P and Berman, Sarah B and Schofield,
                      Peter R and Jucker, Mathias and Levin, Johannes and Lee,
                      Jae-Hong and Perrin, Richard J and Morris, John C and
                      Cruchaga, Carlos and Hassenstab, Jason and Salloway, Stephen
                      P and Lee, Jai-Hyuen and Daniels, Alisha},
      collaboration = {Network, Dominantly Inherited Alzheimer},
      title        = {{A}ssociation of {R}esilience-{R}elated {L}ife
                      {E}xperiences on {V}ariability on {A}ge of {O}nset in
                      {D}ominantly {I}nherited {A}lzheimer {D}isease.},
      journal      = {Neurology},
      volume       = {103},
      number       = {7},
      issn         = {0028-3878},
      address      = {[Erscheinungsort nicht ermittelbar]},
      publisher    = {Ovid},
      reportid     = {DZNE-2024-01139},
      pages        = {e209766},
      year         = {2024},
      abstract     = {It remains unknown whether the associations between
                      protective lifestyles and sporadic dementia risk reported in
                      observational studies also affect age at symptom onset (AAO)
                      in autosomal dominant Alzheimer disease (ADAD) with
                      predominant genetic influences. We investigated the
                      associations between resilience-related life experiences and
                      interindividual AAO variability in ADAD.We performed a
                      longitudinal and confirmatory analysis of the Dominantly
                      Inherited Alzheimer Network prospective observational cohort
                      (January 2009-June 2018, follow-up duration 2.13 ± 2.22
                      years), involving clinical, CSF, and lifestyle/behavioral
                      assessments. We performed a 2-pronged comprehensive
                      resilience assessment in each cohort. Cohort 1,
                      incorporating the general resilience definition (cognitive
                      maintenance [Clinical Dementia Rating = 0] despite high
                      pathology), included carriers during the periods of
                      significant CSFp-tau181 variability and grouped into
                      resilience/resistance outcome bins according to the
                      dichotomous pathologic and cognitive statuses,
                      subcategorized by the estimated years from expected symptom
                      onset (EYO). Cohort 2, focused on ADAD-specific genetically
                      determined time frame characterizing the onset
                      predictability, included asymptomatic participants with
                      available preclinical lifestyle data and AAO outcomes and
                      grouped into delayed or earlier AAO relative to the parental
                      AAO. Associations of cognitive, CSFp-tau181, and
                      lifestyle/behavioral predictors with binary outcomes were
                      investigated using logistic regression.Of 320 carriers (age
                      38.19 ± 10.94 years, female $56.25\%),$ cohort 1 included
                      218 participants (39.00 ± 9.37 years, $57.34\%)$ and cohort
                      2 included 28 participants (43.34 ± 7.40 years, $71.43\%).$
                      In cohort 1, 218 carriers after -20 EYO, when the
                      interindividual variability (SD) of CSFp-tau181 first became
                      more than twice greater in carriers than in noncarriers,
                      were grouped into low-risk control (asymptomatic, low
                      pathology, n = 103), high-resilience (asymptomatic despite
                      high pathology, n = 60), low-resilience (symptomatic despite
                      low pathology, n = 15), and susceptible control
                      (symptomatic, high pathology, n = 40) groups. Multivariable
                      predictors of high resilience, controlling for age and
                      depression, included higher conscientiousness (odds ratio
                      1.051 $[95\%$ CI 1.016-1.086], p = 0.004), openness to
                      experience (1.068 [1.005-1.135], p = 0.03) (vs. susceptible
                      controls), and agreeableness (1.082 [1.015-1.153], p = 0.02)
                      (vs. low resilience). From 1 to 3 years before parental AAO
                      (cohort 2), the multivariable predictor of delayed AAO,
                      controlling for CSFp-tau181, was higher conscientiousness
                      (0.916 [0.845-0.994], p = 0.036).Among the cognitively and
                      socially integrated life experiences associated with
                      resilience, measures of conscientiousness were useful
                      indicators for evaluating resilience and predicting future
                      dementia onset in late preclinical ADAD.},
      keywords     = {Humans / Female / Alzheimer Disease: genetics / Alzheimer
                      Disease: psychology / Alzheimer Disease: epidemiology / Male
                      / Middle Aged / Resilience, Psychological / Age of Onset /
                      Adult / Longitudinal Studies / Cohort Studies / Prospective
                      Studies / tau Proteins: genetics / Life Style / Life Change
                      Events / Aged / tau Proteins (NLM Chemicals)},
      cin          = {AG Jucker / Clinical Research (Munich) / AG Levin},
      ddc          = {610},
      cid          = {I:(DE-2719)1210001 / I:(DE-2719)1111015 /
                      I:(DE-2719)1111016},
      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},
      experiment   = {EXP:(DE-2719)DIAN-20090101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39270149},
      pmc          = {pmc:PMC11399067},
      doi          = {10.1212/WNL.0000000000209766},
      url          = {https://pub.dzne.de/record/272148},
}