Nicotinic α4β2 acetylcholine receptors and cognitive function in Parkinson's disease.
BACKGROUND
Idiopathic Parkinson's disease (IPD) is characterized by the clinical motor symptoms of hypokinesia, rigidity, and tremor. Apart from these motor symptoms, cognitive deficits often occur in IPD. The positive effect of cholinesterase inhibitors on cognitive deficits in IPD and findings of earlier molecular imaging studies suggest that the cholinergic system plays an important role in the origin of cognitive decline in IPD.


METHODS
Twenty-five non-demented patients with IPD underwent a 5-[123I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) SPECT to visualize α4β2 nicotinic acetylcholine receptors (nAchR) and cognitive testing with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery to identify domains of cognitive dysfunction.


RESULTS
In the CERAD, the IPD patients exhibited deficits in non-verbal memory, attention, psychomotor velocity, visuoconstructive ability, and executive functions. After Bonferroni correction for multiple comparisons, we found significant correlations between performance of the CERAD subtests Boston Naming Test (a specific test for visual perception and for detection of word-finding difficulties) and Word List Intrusions (a specific test for learning capacity and memory for language information) vs binding of α4β2 nAchR in cortical (the right superior parietal lobule) and subcortical areas (the left thalamus, the left posterior subcortical region, and the right posterior subcortical region).


CONCLUSIONS
These significant correlations between the results of the CERAD subtests and the cerebral α4β2 nAchR density, as assessed by 5-I-A-85380 SPECT, indicate that cerebral cholinergic pathways are relevant to cognitive processing in IPD.
Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
R
R
Lorenz
S
S
Samnick
U
U
Dillmann
M
M
Schiller
M F
MF
Ong
K
K
Faßbender
A
A
Buck
J
J
Spiegel
D000368:Aged; D001384:Azetidines; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
C104288:A 85380; D001384:Azetidines; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2
5-I-A-85380-SPECT; Parkinson's disease; cognitive deficits; α4β2 nicotinic acetylcholine receptors