title: Neuropsychiatric symptoms of cholinergic deficiency occur with degradation of the projections from the nucleus basalis of Meynert.
abstract: This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosis.
authors: Department of Neurology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. j.vandalen@amc.nl.
authors: Jan Willem
authors: JW
authors: van Dalen
authors: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors: Matthan W A
authors: MWA
authors: Caan
authors: Department of Neurology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.
authors: Willem A
authors: WA
authors: van Gool
authors: Department of Neurology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.|Department of Neurology, Radboud University Medical Center, Nijmegen, Netherlands.
authors: Edo
authors: E
authors: Richard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D020532:Basal Nucleus of Meynert / Q000000981:diagnostic imaging* / Q000473:pathology; D059329:Cholinergic Neurons / Q000473:pathology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: Acetyl cholinesterase; Behavioral symptoms; Dementia; Neurodegeneration; Tractography; White matter; White matter hyperintensities