PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease.
BACKGROUND
Patients suffering from Alzheimer's disease (AD) experience a marked reduction in cortical nicotinic acetylcholine receptors (nAChRs). In particular, selective loss of the alpha4beta2 nAChR subtype was observed in postmortem AD brain tissue. The alpha4 and alpha7 nAChR subunits were suggested to play an important role in cognitive function. Positron emission tomography (PET) has so far been used to visualize neuronal nAChRs in vivo by 11C-nicotine binding.


OBJECTIVE
To investigate the relationship between measures of cognitive function and in vivo 11C-nicotine binding in mild AD brain as assessed by PET.


METHODS
Twenty-seven patients with mild AD were recruited in this study. A dual tracer model with administration of 15O-water for regional cerebral blood flow and (S)(-)11C-nicotine was used to assess nicotine binding sites in the brain by PET. Cognitive function was assessed using neuropsychological tests of global cognition, episodic memory, attention, and visuospatial ability.


RESULTS
Mean cortical 11C-nicotine binding significantly correlated with the results of attention tests [Digit Symbol test (r = -0.44 and p = 0.02) and Trail Making Test A (TMT-A) (r = 0.42 and p = 0.03)]. No significant correlation was observed between 11C-nicotine binding and the results of tests of episodic memory or visuospatial ability. Regional analysis showed that 11C-nicotine binding in the frontal and parietal cortex, which are the main areas for attention, correlated significantly with the Digit Symbol test and TMT-A results.


CONCLUSIONS
Cortical nicotinic receptors in vivo in mild AD patients are robustly associated with the cognitive function of attention.
Kadir
Ahmadul
A
Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Novum Floor-5, Stockholm, 141 86, Sweden.
Almkvist
Ove
O
Wall
Anders
A
Långström
Bengt
B
Nordberg
Agneta
A
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D001288:Attention / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003071:Cognition / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D009483:Neuropsychological Tests; D009538:Nicotine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011978:Receptors, Nicotinic / Q000502:physiology
D002250:Carbon Radioisotopes; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine