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@ARTICLE{Mourtzi:163660,
author = {Mourtzi, N. and Hatzimanolis, A. and Xiromerisiou, G. and
Ntanasi, E. and Georgakis, M. K. and Ramirez, A. and
Heilmann-Heimbach, S. and Grenier-Boley, B. and Lambert, J.
C. and Yannakoulia, M. and Kosmidis, M. and Dardiotis, E.
and Hadjigeorgiou, G. and Sakka, P. and Scarmeas, N.},
title = {{A}ssociation between 9p21-23 {L}ocus and {F}railty in a
{C}ommunity-{D}welling {G}reek {P}opulation: {R}esults from
the {H}ellenic {L}ongitudinal {I}nvestigation of {A}geing
and {D}iet.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {9},
number = {1},
issn = {2274-5807},
address = {Cham},
publisher = {Springer International Publishing},
reportid = {DZNE-2022-00406},
pages = {77-85},
year = {2022},
abstract = {Frailty is a complex geriatric syndrome arising from a
combination of genetic and environmental factors and is
associated with adverse health outcomes and mortality. A
recent study reported an association between variants of the
9p21-23 locus, associated with a number of age-related
disorders, including Alzheimer's disease (AD), and frailty.
Frailty has been associated with increased risk of
developing AD and it has been proposed that frailty burden
may modify AD clinical presentation. In view of the
overlapping genetic architecture between the two disorders,
it is noteworthy to conduct studies to uncover risk variants
that contribute to both AD and frailty. The purpose of this
study is to test the reproducibility of the association of
9p21-23 locus with frailty in a population that is
ethnically different from previous work and in the context
of multidimensional definitions of frailty that will allow
us to examine the potential impact to domains pertaining to
AD pathology.We operationalized frailty according two
definitions and the corresponding instruments, the Frailty
Index (FI) and the Tilburg Frailty Indicator (TFI) and we
determined genotypes of eight alleles previously identified
as risk increasing for frailty in 1172 community-dwelling
older participants $(57\%$ females) from the HELIAD study
with a mean age of 74 years old. We cross-sectionally
investigated the association between risk alleles and
frailty, as well as with specific components of each
definition using linear regression analyses adjusted for
age, sex and years of education.Compared to non-carriers,
carriers of rs7038172 C risk allele, were associated with a
higher FI Score (β=0.089, p=0.002). Similarly, we found a
positive association between the presence of at least one
rs7038172 C variant and TFI score (β=0.053, p=0.04).
Moreover, the rs7038172 variant was associated,
irrespectively of dementia status, with the memory and
psychological domain of FI and TFI, respectively.Our study
confirms the association of the rs7038172 C allele with the
frailty syndrome in a Greek population and in the context of
multidimensional definitions of frailty. Furthermore, we
report novel associations between this allele and the memory
domain of FI and the psychological domain of TFI, that
includes memory problems on its components. Given that
frailty burden has been shown to modify the AD clinical
presentation, it is likely that rs7038172 C allele may
accelerate the transition of AD or frailty to dementia
Overall, our study corroborates the role of the 9p21-23
region in frailty development and draw potential links with
AD pathology.},
keywords = {9p21-23 locus (Other) / Alzheimer (Other) / Frailty (Other)
/ genetics (Other)},
cin = {Patient Studies (Bonn)},
ddc = {610},
cid = {I:(DE-2719)1011101},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35098976},
doi = {10.14283/jpad.2022.2},
url = {https://pub.dzne.de/record/163660},
}