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Noradrenergic contributions to cognitive decline and treatment potential in progressive supranuclear palsy and Parkinson’s disease
Author(s) -
Rowe James B.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044767
Subject(s) - locus coeruleus , progressive supranuclear palsy , neuromelanin , neuroscience , parkinson's disease , medicine , psychology , pathology , disease , substantia nigra , central nervous system
Abstract Background The Locus coeruleus is the principal source of Noradrenaline to the cerebrum, modulating diverse functions from attentional and behavioural control, learning and perception, arousal and autonomic control. The locus coeruleus is vulnerable to many neurodegenerative disorders, with post‐mortem evidence of early and substantial cell loss in Alzheimer’s disease, Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP). The relevance of locus coeruleus pathology and noradrenergic denervation in vivo has come largely from psychopharmacological studies, and PET imaging of the noradrenergic transporter. Method We exploited advances in ultra‐high field magnetic resonance imaging at 7T that now provide excellent sensitivity to the loss of neuromelanin containing neurons in the locus coeruleus, enabling quantification of the spatial extent and signal intensity (cf. cell density) in patients. We developed an optimised atlas of locus coeruleus in older adults (>50), and applied this to independent cohorts of patients with idiopathic Parkinson’s disease and PSP (Richardson’s syndrome) with a magnetisation transfer weighted sequence to scan the brain stem at 7T. Result Patients in both groups showed a marked reduction in locus coeruleus signal intensity, relative to a mid‐pontine reference regions, especially in the caudal locus coeruleus. In Parkinson’s disease, the contrast‐to‐noise of the locus coeruleus correlated with apathy and motor disease severity. A corresponding reduction of noradrenergic cells was confirmed at post‐mortem in a parallel group of patients with PSP, in whom cell loss was proportional to disease severity. Conclusion 7T MRI is well tolerated and sensitive to pathology of the locus coeruleus in PSP and PD. We propose the use of 7T‐MRI to quantify the integrity of the locus coeruleus in stratified trials of therapeutic strategies for cognitive and motor control in neurodegenerative disease.