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000139720 1001_ $$aRay, Nicola J$$b0
000139720 245__ $$aIn vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson's disease.
000139720 260__ $$aOxford$$bOxford Univ. Press$$c2018
000139720 264_1 $$2Crossref$$3online$$bOxford University Press (OUP)$$c2017-12-08
000139720 264_1 $$2Crossref$$3print$$bOxford University Press (OUP)$$c2018-01-01
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000139720 520__ $$aSee 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.
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000139720 650_7 $$2NLM Chemicals$$aCholinergic Agents
000139720 650_2 $$2MeSH$$aAged
000139720 650_2 $$2MeSH$$aAtrophy
000139720 650_2 $$2MeSH$$aBasal Forebrain: diagnostic imaging
000139720 650_2 $$2MeSH$$aBasal Forebrain: metabolism
000139720 650_2 $$2MeSH$$aBrain Mapping
000139720 650_2 $$2MeSH$$aCholinergic Agents: metabolism
000139720 650_2 $$2MeSH$$aCognition Disorders: diagnosis
000139720 650_2 $$2MeSH$$aCognition Disorders: etiology
000139720 650_2 $$2MeSH$$aCognition Disorders: pathology
000139720 650_2 $$2MeSH$$aDisease Progression
000139720 650_2 $$2MeSH$$aFemale
000139720 650_2 $$2MeSH$$aHumans
000139720 650_2 $$2MeSH$$aImage Processing, Computer-Assisted
000139720 650_2 $$2MeSH$$aLongitudinal Studies
000139720 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000139720 650_2 $$2MeSH$$aMale
000139720 650_2 $$2MeSH$$aMiddle Aged
000139720 650_2 $$2MeSH$$aMotor Activity
000139720 650_2 $$2MeSH$$aNeuropsychological Tests
000139720 650_2 $$2MeSH$$aParkinson Disease: complications
000139720 650_2 $$2MeSH$$aROC Curve
000139720 7001_ $$aBradburn, Steven$$b1
000139720 7001_ $$aMurgatroyd, Christopher$$b2
000139720 7001_ $$aToseeb, Umar$$b3
000139720 7001_ $$aMir, Pablo$$b4
000139720 7001_ $$aKountouriotis, George K$$b5
000139720 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan J$$b6$$udzne
000139720 7001_ $$0P:(DE-2719)2810708$$aGrothe, Michel J$$b7$$eLast author$$udzne
000139720 77318 $$2Crossref$$3journal-article$$a10.1093/brain/awx310$$b : Oxford University Press (OUP), 2017-12-08$$n1$$p165-176$$tBrain$$v141$$x0006-8950$$y2017
000139720 773__ $$0PERI:(DE-600)1474117-9$$a10.1093/brain/awx310$$gVol. 141, no. 1, p. 165 - 176$$n1$$p165-176$$q141:1<165 - 176$$tBrain$$v141$$x0006-8950$$y2017
000139720 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837422
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