Depression and Dementia in Parkinson's Disease: Catecholamine Changes in the Locus coeruleus - Basis for Therapy

1991 ◽  
Vol 2 (1) ◽  
pp. 7-17 ◽  
Author(s):  
V. Chan-Palay
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus

Comparison of Locus Coeruleus Pathology with Nigral and Forebrain Pathology in Parkinson's Disease

2021 ◽  
Author(s):  
Benjamin Huynh ◽  
Yuhong Fu ◽  
Deniz Kirik ◽  
James M. Shine ◽  
Glenda M. Halliday
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus

scholarly journals Locus Coeruleus atrophy doesn’t relate to fatigue in Parkinson’s disease

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Oleg Solopchuk ◽  
Moustapha Sebti ◽  
Céline Bouvy ◽  
Charles-Etienne Benoit ◽  
Thibault Warlop ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus

Changes in substantia nigra and locus coeruleus in patients with early-stage Parkinson's disease using neuromelanin-sensitive MR imaging

2013 ◽  
Vol 541 ◽  
pp. 93-98 ◽  
Author(s):  
Chigumi Ohtsuka ◽  
Makoto Sasaki ◽  
Kanako Konno ◽  
Mizuho Koide ◽  
Kanako Kato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mr Imaging ◽  
Locus Coeruleus ◽  
Early Stage

scholarly journals Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson's disease

2020 ◽  
Author(s):  
Claire O'Callaghan ◽  
Frank Hubert Hezemans ◽  
Rong Ye ◽  
Catarina Rua ◽  
P Simon Jones ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus ◽  
Response Inhibition ◽  
Therapeutic Potential ◽  
Reaction Times ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Double Blind ◽  
Caudal Portion

Cognitive decline is a common feature of Parkinson's disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson's disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson's disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson's disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.

Sign in / Sign up

Export Citation Format

Share Document