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@ARTICLE{Hoenig:285017,
author = {Hoenig, Merle C and Dzialas, Verena and Doering, Elena and
Bischof, Gérard N and Eimeren, Thilo and Drzezga,
Alexander},
collaboration = {Initiative, Alzheimer’s Disease Neuroimaging},
title = {{M}odifiable {F}actors {A}ssociated with the {L}ongitudinal
{I}ncrease and {S}patial {E}xtent of {T}au {P}athology in
{A}lzheimer {D}isease.},
journal = {Journal of nuclear medicine},
volume = {67},
number = {2},
issn = {0097-9058},
address = {New York, NY},
publisher = {Soc.},
reportid = {DZNE-2026-00143},
pages = {291-296},
year = {2026},
abstract = {There are 14 modifiable factors that are associated with a
significantly lower risk of dementia. We tested the
interactive effect of modifiable factors, genetic
determinants, and initial pathologic burden on the spatial
progression and local amplification of tau pathology.
Methods: In total, 162 amyloid-positive individuals were
included, for whom longitudinal [18F]AV-1451 PET scans,
baseline information on global amyloid burden, ApoE4 status,
body mass index (BMI), hypertension, education,
neuropsychiatric symptom severity, and demographic
information were available in the Alzheimer Disease
Neuroimaging Initiative. All [18F]AV-1451 scans were
intensity-standardized (reference: inferior cerebellum),
z-transformed (control sample: 147 amyloid-negative
subjects), thresholded (z score, >1.96), and converted to
volume maps. Longitudinal tau changes were then assessed in
terms of tau spatial extent (i.e., newly affected volume at
follow-up) and tau level rise (i.e., tau increase in
previously affected volume). These 2 measures were entered
as dependent variables in linear mixed-effects models,
including baseline modifiable risk factors (BMI, education,
hypertension, neuropsychiatric symptom severity), global
amyloid, tau volume or tau burden, ApoE4 status, clinical
stage, sex, and age as predictors. Next, we tested the
interactive effects between baseline amyloid or tau burden
with the 4 modifiable factors on tau extent or tau level
rise, respectively. Results: Greater tau extent was linked
to higher BMI (β = 0.002; $95\%$ CI, 0.0003-0.003), ApoE4
status (β = 0.024; $95\%$ CI, 0.001-0.046), and baseline
tau volume (β = 0.207; $95\%$ CI, 0.107-0.308) across
groups. In terms of tau level rise, we observed that absence
of hypertension (β = 0.295; $95\%$ CI, -0.477 to -0.114),
dementia group (β = 0.305; $95\%$ CI, 0.088-0.522), and BMI
(β = 0.011; $95\%$ CI, 0.00004-0.022) were linked to
increased tau burden. A load-dependent effect of baseline
amyloid and tau volume/burden was found for both tau extent
(β = -0.005; $95\%$ CI, -0.008 to -0.002) and tau level
rise (β = -0.003; $95\%$ CI, -0.005 to -0.001). Higher
amyloid and BMI (β = 0.001; $95\%$ CI, 0.0004-0.001) and
lower education and higher tau burden (β = -0.035; $95\%$
CI, -0.064 to -0.006) were linked to greater tau level rise.
Conclusion: Education, BMI, and hypertension differentially
influence tau's spatial extent and increase by its
interaction with initial pathologic burden. Timely
modification of these factors may overall slow tau
progression.},
keywords = {Humans / tau Proteins: metabolism / Male / Alzheimer
Disease: diagnostic imaging / Alzheimer Disease: metabolism
/ Alzheimer Disease: pathology / Female / Aged /
Longitudinal Studies / Positron-Emission Tomography /
Carbolines / Aged, 80 and over / Middle Aged / Body Mass
Index / Risk Factors / (non-)modifiable risk factors (Other)
/ spatial extent (Other) / tau pathology (Other) / tau
Proteins (NLM Chemicals) /
7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (NLM
Chemicals) / Carbolines (NLM Chemicals)},
cin = {AG Boecker},
ddc = {610},
cid = {I:(DE-2719)1011202},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41266256},
pmc = {pmc:PMC12866421},
doi = {10.2967/jnumed.125.270593},
url = {https://pub.dzne.de/record/285017},
}