Original Investigation

Psychopharmacology

, Volume 188, Issue 4, pp 509-520

First online:

PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer’s disease

  • Ahmadul KadirAffiliated withDepartment of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge
  • , Ove AlmkvistAffiliated withDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital HuddingeDepartment of Geriatric Medicine, Karolinska University Hospital HuddingeDepartment of Psychology, Stockholm University
  • , Anders WallAffiliated withUppsala Imanet
  • , Bengt LångströmAffiliated withUppsala Imanet
  • , Agneta NordbergAffiliated withDepartment of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Karolinska Institutet, Karolinska University Hospital HuddingeDepartment of Geriatric Medicine, Karolinska University Hospital Huddinge Email author 

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Abstract

Rationale

Patients suffering from Alzheimer’s disease (AD) experience a marked reduction in cortical nicotinic acetylcholine receptors (nAChRs). In particular, selective loss of the α4β2 nAChR subtype was observed in postmortem AD brain tissue. The α4 and α7 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.

Objectives

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

Materials and 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.

Conclusion

Cortical nicotinic receptors in vivo in mild AD patients are robustly associated with the cognitive function of attention.

Keywords

Alzheimer’s disease (AD) Nicotinic acetylcholine receptors (nAChRs) Positron emission tomography (PET) 11C-nicotine binding Cognition Attention