Alterations in Phase-Related Prefrontal Activation During Cognitive Tasks and Nicotinic α4β2 Receptor Availability in Alzheimer's Disease.
Evidence shows that the cholinergic system plays an important role in regulating working memory and that working memory-related prefrontal activation decreases with age and neuronal degeneration, such as Alzheimer's disease (AD). However, the relation between attention-related α4β2 nicotinic cholinergic function and task-induced prefrontal activation especially time course-related activation remains to be explored.



We aimed to elucidate the relationship between changes in task-induced oxy-hemoglobin concentration (cerebral blood flow, CBF) in the prefrontal cortex and the availability of α4β2 nicotinic receptors in the brain of AD patients in light of their task performance.



Eleven mild-to-moderate AD patients and eleven normal elderly subjects underwent the near-infrared spectroscopy during easy and difficult working memory tasks for estimating prefrontal CBF changes and positron emission tomography with the α4β2 tracer [18F]2FA-85380 ([18F]2FA) for measuring the α4β2 nicotinic receptor binding.



Significant correlations between mean oxy-hemoglobin concentration in the channels with significant [group] main effects and prefrontal [18F]2FA binding were observed during the early easy task period in the normal group and during the late difficult task in the AD group. In addition, those prefrontal CBF responses were significantly correlated with not correct performance but the execution time to spend.



The α4β2 nicotinic acetylcholine receptors in the prefrontal cortex play an important role in increasing prefrontal activation when attending to novel stimuli, irrespective of the accuracy of the outcome. A delay in the cholinergic-induced increase in prefrontal activation in AD patients might explain their delayed responses in the cognitive task.
Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yumi
Y
Oboshi
Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.
Mitsuru
M
Kikuchi
Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Tatsuhiro
T
Terada
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Japan.
Etsuji
E
Yoshikawa
Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Tomoyasu
T
Bunai
Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yasuomi
Y
Ouchi
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D001384:Azetidines / Q000493:pharmacokinetics; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D010108:Oxyhemoglobins / Q000378:metabolism; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared; D013223:Statistics as Topic
C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D010108:Oxyhemoglobins; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2
Alzheimer’s disease; cerebral blood flow; nicotinic acetylcholine receptor; prefrontal cortex; working memory