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@ARTICLE{Ray:139720,
author = {Ray, Nicola J and Bradburn, Steven and Murgatroyd,
Christopher and Toseeb, Umar and Mir, Pablo and
Kountouriotis, George K and Teipel, Stefan J and Grothe,
Michel J},
title = {{I}n vivo cholinergic basal forebrain atrophy predicts
cognitive decline in de novo {P}arkinson's disease.},
journal = {Brain},
volume = {141},
number = {1},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2020-06042},
pages = {165-176},
year = {2018},
abstract = {See Gratwicke and Foltynie (doi:10.1093/brain/awx333) for a
scientific commentary on this article.Cognitive impairments
are a prevalent and disabling non-motor complication of
Parkinson's disease, but with variable expression and
progression. The onset of serious cognitive decline occurs
alongside substantial cholinergic denervation, but
imprecision of previously available techniques for in vivo
measurement of cholinergic degeneration limit their use as
predictive cognitive biomarkers. However, recent
developments in stereotactic mapping of the cholinergic
basal forebrain have been found useful for predicting
cognitive decline in prodromal stages of Alzheimer's
disease. These methods have not yet been applied to
longitudinal Parkinson's disease data. In a large sample of
people with de novo Parkinson's disease (n = 168), retrieved
from the Parkinson's Progressive Markers Initiative
database, we measured cholinergic basal forebrain volumes,
using morphometric analysis of T1-weighted images in
combination with a detailed stereotactic atlas of the
cholinergic basal forebrain nuclei. Using a binary
classification procedure, we defined patients with reduced
basal forebrain volumes (relative to age) at baseline, based
on volumes measured in a normative sample (n = 76).
Additionally, relationships between the basal forebrain
volumes at baseline, risk of later cognitive decline, and
scores on up to 5 years of annual cognitive assessments were
assessed with regression, survival analysis and linear mixed
modelling. In patients, smaller volumes in a region
corresponding to the nucleus basalis of Meynert were
associated with greater change in global cognitive, but not
motor scores after 2 years. Using the binary classification
procedure, patients classified as having smaller than
expected volumes of the nucleus basalis of Meynert had
∼3.5-fold greater risk of being categorized as mildly
cognitively impaired over a period of up to 5 years of
follow-up (hazard ratio = 3.51). Finally, linear mixed
modelling analysis of domain-specific cognitive scores
revealed that patients classified as having smaller than
expected nucleus basalis volumes showed more severe and
rapid decline over up to 5 years on tests of memory and
semantic fluency, but not on tests of executive function.
Thus, we provide the first evidence that volumetric
measurement of the nucleus basalis of Meynert can predict
early cognitive decline. Our methods therefore provide the
opportunity for multiple-modality biomarker models to
include a cholinergic biomarker, which is currently lacking
for the prediction of cognitive deterioration in Parkinson's
disease. Additionally, finding dissociated relationships
between nucleus basalis status and domain-specific cognitive
decline has implications for understanding the neural basis
of heterogeneity of Parkinson's disease-related cognitive
decline.},
keywords = {Aged / Atrophy / Basal Forebrain: diagnostic imaging /
Basal Forebrain: metabolism / Brain Mapping / Cholinergic
Agents: metabolism / Cognition Disorders: diagnosis /
Cognition Disorders: etiology / Cognition Disorders:
pathology / Disease Progression / Female / Humans / Image
Processing, Computer-Assisted / Longitudinal Studies /
Magnetic Resonance Imaging / Male / Middle Aged / Motor
Activity / Neuropsychological Tests / Parkinson Disease:
complications / ROC Curve / Cholinergic Agents (NLM
Chemicals)},
cin = {Clinical Dementia Research Rostock /Greifswald ; AG Teipel},
ddc = {610},
cid = {I:(DE-2719)1510100},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29228203},
pmc = {pmc:PMC5837422},
doi = {10.1093/brain/awx310},
url = {https://pub.dzne.de/record/139720},
}