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@ARTICLE{Chhatwal:139950,
author = {Chhatwal, Jasmeer P and Schultz, Aaron P and Johnson, Keith
A and Hedden, Trey and Jaimes, Sehily and Benzinger, Tammie
L S and Jack, Clifford and Ances, Beau M and Ringman, John M
and Marcus, Daniel S and Ghetti, Bernardino and Farlow,
Martin R and Danek, Adrian and Levin, Johannes and Yakushev,
Igor and Laske, Christoph and Koeppe, Robert A and Galasko,
Douglas R and Xiong, Chengjie and Masters, Colin L and
Schofield, Peter R and Kinnunen, Kirsi M and Salloway,
Stephen and Martins, Ralph N and McDade, Eric and Cairns,
Nigel J and Buckles, Virginia D and Morris, John C and
Bateman, Randall and Sperling, Reisa A and Network,
Dominantly Inherited Alzheimer},
title = {{P}referential degradation of cognitive networks
differentiates {A}lzheimer's disease from ageing.},
journal = {Brain},
volume = {141},
number = {5},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2020-06272},
pages = {1486-1500},
year = {2018},
abstract = {Converging evidence from structural, metabolic and
functional connectivity MRI suggests that neurodegenerative
diseases, such as Alzheimer's disease, target specific
neural networks. However, age-related network changes
commonly co-occur with neuropathological cascades, limiting
efforts to disentangle disease-specific alterations in
network function from those associated with normal ageing.
Here we elucidate the differential effects of ageing and
Alzheimer's disease pathology through simultaneous analyses
of two functional connectivity MRI datasets: (i) young
participants harbouring highly-penetrant mutations leading
to autosomal-dominant Alzheimer's disease from the
Dominantly Inherited Alzheimer's Network (DIAN), an
Alzheimer's disease cohort in which age-related
comorbidities are minimal and likelihood of progression
along an Alzheimer's disease trajectory is extremely high;
and (ii) young and elderly participants from the Harvard
Aging Brain Study, a cohort in which imaging biomarkers of
amyloid burden and neurodegeneration can be used to
disambiguate ageing alone from preclinical Alzheimer's
disease. Consonant with prior reports, we observed the
preferential degradation of cognitive (especially the
default and dorsal attention networks) over motor and
sensory networks in early autosomal-dominant Alzheimer's
disease, and found that this distinctive degradation pattern
was magnified in more advanced stages of disease.
Importantly, a nascent form of the pattern observed across
the autosomal-dominant Alzheimer's disease spectrum was also
detectable in clinically normal elderly with clear biomarker
evidence of Alzheimer's disease pathology (preclinical
Alzheimer's disease). At the more granular level of
individual connections between node pairs, we observed that
connections within cognitive networks were preferentially
targeted in Alzheimer's disease (with between network
connections relatively spared), and that connections between
positively coupled nodes (correlations) were preferentially
degraded as compared to connections between negatively
coupled nodes (anti-correlations). In contrast, ageing in
the absence of Alzheimer's disease biomarkers was
characterized by a far less network-specific degradation
across cognitive and sensory networks, of between- and
within-network connections, and of connections between
positively and negatively coupled nodes. We go on to
demonstrate that formalizing the differential patterns of
network degradation in ageing and Alzheimer's disease may
have the practical benefit of yielding connectivity
measurements that highlight early Alzheimer's
disease-related connectivity changes over those due to
age-related processes. Together, the contrasting patterns of
connectivity in Alzheimer's disease and ageing add to prior
work arguing against Alzheimer's disease as a form of
accelerated ageing, and suggest multi-network composite
functional connectivity MRI metrics may be useful in the
detection of early Alzheimer's disease-specific alterations
co-occurring with age-related connectivity changes. More
broadly, our findings are consistent with a specific pattern
of network degradation associated with the spreading of
Alzheimer's disease pathology within targeted neural
networks.},
keywords = {Adult / Aged / Aged, 80 and over / Aging / Alzheimer
Disease: complications / Alzheimer Disease: diagnostic
imaging / Alzheimer Disease: genetics / Aniline Compounds:
pharmacokinetics / Brain Mapping / Cognition Disorders:
diagnostic imaging / Cognition Disorders: etiology / Female
/ Fluorodeoxyglucose F18: pharmacokinetics / Humans /
Magnetic Resonance Imaging / Male / Middle Aged / Models,
Neurological / Neural Pathways: diagnostic imaging / Neural
Pathways: drug effects / Positron-Emission Tomography /
Thiazoles: pharmacokinetics /
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (NLM
Chemicals) / Aniline Compounds (NLM Chemicals) / Thiazoles
(NLM Chemicals) / Fluorodeoxyglucose F18 (NLM Chemicals)},
cin = {U Clinical Researchers - München / Clinical Dementia
Research München / München Pre 2020 / AG Jucker},
ddc = {610},
cid = {I:(DE-2719)7000003 / I:(DE-2719)1111016 /
I:(DE-2719)6000016 / I:(DE-2719)1210001},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
- Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29522171},
pmc = {pmc:PMC5917745},
doi = {10.1093/brain/awy053},
url = {https://pub.dzne.de/record/139950},
}