Reduced alpha4beta2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkinson disease.
BACKGROUND
Cognitive or depressive disorders are frequently noted in patients with Parkinson disease (PD) and may be related to altered signaling through alpha4beta2*-nicotinic acetylcholine receptors (alpha4beta2*-nAChRs).


OBJECTIVE
To assess the availability of alpha4beta2*-nAChRs and their relationship to mild cognitive and mild depressive symptoms in vivo in patients with PD.


METHODS
Crossover comparison between patients with PD and healthy volunteers (control group) using the alpha4beta2*-nAChR-specific radioligand 2-[(18)F]fluoro-3-(2[S]-2-azetidinylmethoxy)-pyridine (2-[(18)F]FA-85380) and positron emission tomography.


METHODS
Departments of Neurology and Nuclear Medicine, University of Leipzig, Leipzig, Germany.


METHODS
Twenty-two nonsmoking patients with PD and 9 nonsmoking healthy volunteers.


METHODS
Level of 2-[(18)F]FA-85380 binding potential (2-FA BP), a measure of alpha4beta2*-nAChR availability. The relationship between severity of cognitive symptoms as rated using the Mini-Mental State Examination and DemTect scale and the level of depressive symptoms as indicated using the Beck Depression Inventory, and 2-FA BP were assessed.


RESULTS
In patients with PD compared with healthy volunteers, there was widespread reduced 2-FA BP, especially in the midbrain, pons, anterior cingulate cortex, frontoparietal cortex, and cerebellum. In subgroups of patients with PD with possible depression, reduced 2-FA BP was most pronounced in the cingulate cortex and frontoparieto-occipital cortex, whereas in patients with PD with mild cognitive impairment, 2-FA BP was reduced in the midbrain, pons, and cerebellum. In patients with PD, the strongest associations between depressive symptoms and reduced 2-FA BP were noted in the anterior cingulate cortex, putamen, midbrain, and occipital cortex. In contrast, cognitive symptoms correlated only weakly with reduced 2-FA BP in the thalamus, midbrain, temporal cortex, hippocampus, and cerebellum.


CONCLUSIONS
There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced alpha4beta2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.
Meyer
Philipp M
PM
Department of Nuclear Medicine, University of Leipzig, Liebigstr 18, 04103 Leipzig, Germany. philipp.meyer@medizin.uni-leipzig.de
Strecker
Karl
K
Kendziorra
Kai
K
Becker
Georg
G
Hesse
Swen
S
Woelpl
Dominique
D
Hensel
Anke
A
Patt
Marianne
M
Sorger
Dietlind
D
Wegner
Florian
F
Lobsien
Donald
D
Barthel
Henryk
H
Brust
Peter
P
Gertz
Hermann J
HJ
Sabri
Osama
O
Schwarz
Johannes
J
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003072:Cognition Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D003863:Depression / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D010555:Personality Inventory; D049268:Positron-Emission Tomography; D011869:Radioligand Assay / Q000706:statistics & numerical data; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012720:Severity of Illness Index; D014018:Tissue Distribution
D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2