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@INPROCEEDINGS{He:283147,
author = {He, Bing and Ospina, Paula and Espinosa, Alejandro and
Becerra-Mateus, Juan Camilo and Osorio, Laura and Alzate,
Diana and Alvarez, Sergio and Grazia, Alice and Teipel,
Stefan and Malotaux, Vincent and Tristão-Pereira, Catarina
and Rowe, Meredith and Giudicessi, Averi and Carmo, Sonia Do
and Niño, David Fernando Aguillón and Cuello, A. Claudio
and Quiroz, Yakeel T.},
title = {{E}arly changes in basal forebrain volume and cognitive
function in preclinical autosomal dominant {A}lzheimer's
disease},
journal = {Alzheimer's and dementia},
volume = {21},
number = {S2},
issn = {1552-5260},
reportid = {DZNE-2026-00043},
pages = {e105027},
year = {2025},
abstract = {Background: The basal forebrain (BF), home to cholinergic
neurons essential for attention and memory undergoes
structural changes in sporadic Alzheimer's Disease and in
at-risk individuals, contributing to cognitive decline. To
investigate whether BF volume is reduced in preclinical
autosomal-dominant Alzheimer's disease (ADAD), we studied
cognitively-unimpaired carriers of the PSEN1 E280A mutation
from the Colombian kindred, the largest ADAD cohort with a
single mutation, known for early cognitive decline (mild
cognitive impairment at age 44, dementia at 49). Age was
used as a proxy for disease progression to analyze BF volume
and its relationship with age and cognitive performance.
Method: This study included 127 cognitively-unimpaired
individuals from the PSEN1 Colombian kindred (60 carriers,
67 non-carriers; mean-age: 30.67 ± 6.65 years;
mean-education: 12.24 ± 3.06 years). Unimpaired status was
defined by Functional Assessment Staging (FAST) scores <2.
Participants underwent structural MRI and cognitive testing,
with BF volumes measured using a cholinergic nuclei map.
Cognition was assessed with the Mini-Mental State
Examination (MMSE) and the CERAD Word List Learning (WLL)
task. BF volume differences between groups were assessed
using a t-test, and partial Pearson correlations (adjusted
for sex, education, and intracranial volume) were used to
evaluate relationships between BF volume, age, and
cognition. Result: BF volumes did not differ significantly
between carriers (693.83 ± 68.3 mm3) and non-carriers
(694.00 ± 65.24 mm3) (p = 0.82). Age was negatively
correlated with BF volume in the overall sample (r = -0.41,
p = 2.7e-06), carriers (r = -0.41, p = 0.001), and
non-carriers (r = -0.44, p = 2.6e-04). However, BF volume
showed no significant correlation with MMSE or WLL in the
overall sample, carriers, or non-carriers. Conclusion: These
findings suggest that Alzheimer's-related volumetric changes
in the basal forebrain may not manifest during the early
preclinical stages of ADAD. This highlights the importance
of future studies incorporating longitudinal measures to
track BF changes over time, spanning the continuum from
preclinical to clinical stages. Such research could provide
critical insights into the temporal dynamics of BF
involvement and its potential as a marker for early
detection or therapeutic target in ADAD.},
month = {Jul},
date = {2025-07-27},
organization = {Alzheimer’s Association
International Conference, Toronto
(Canada), 27 Jul 2025 - 31 Jul 2025},
cin = {AG Teipel},
ddc = {610},
cid = {I:(DE-2719)1510100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
doi = {10.1002/alz70856_105027},
url = {https://pub.dzne.de/record/283147},
}