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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},
}