Ahmadul Kadir1, Ove Almkvist, Anders Wall, Bengt Långström, Agneta Nordberg. 1. Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Novum Floor-5, Stockholm, 141 86, Sweden.
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 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. 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.
RATIONALE: 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. 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 ADpatients are robustly associated with the cognitive function of attention.
Authors: S J Teipel; F Willoch; K Ishii; K Bürger; A Drzezga; R Engel; P Bartenstein; H-J Möller; M Schwaiger; H Hampel Journal: Neurobiol Aging Date: 2006-05 Impact factor: 4.673
Authors: A Nordberg; H Lundqvist; P Hartvig; J Andersson; M Johansson; E Hellstrŏm-Lindahi; B Långström Journal: Dement Geriatr Cogn Disord Date: 1997 Mar-Apr Impact factor: 2.959
Authors: A Nordberg; P Hartvig; A Lilja; M Viitanen; K Amberla; H Lundqvist; Y Andersson; J Ulin; B Winblad; B Långström Journal: J Neural Transm Park Dis Dement Sect Date: 1990
Authors: Mattis B Wigestrand; Yann S Mineur; Christopher J Heath; Frode Fonnum; Marina R Picciotto; Sven Ivar Walaas Journal: J Neurochem Date: 2011-09-01 Impact factor: 5.372
Authors: Ze Wang; María Fernández-Seara; David C Alsop; Wen-Ching Liu; Judy F Flax; April A Benasich; John A Detre Journal: Neuroimage Date: 2007-10-05 Impact factor: 6.556
Authors: Gary W Small; Susan Y Bookheimer; Paul M Thompson; Greg M Cole; S-C Huang; Vladimir Kepe; Jorge R Barrio Journal: Lancet Neurol Date: 2008-02 Impact factor: 44.182