Purpose: We previously reported delayed task-related cerebral blood flow (CBF) responses in the prefrontal cortex (PFC) of Alzheimer's disease (AD) patients relative to healthy old controls (HC) during visual working memory task. Because we recently showed that CBF changes during the pre-task period were related to cognitive declines in normal aging, we here report the effect in the dementia brain and whether the CBF changes seen in AD may relate to the α4β2 acetylcholine receptor (nAchR) binding that has been altered in AD using near-infrared spectroscopy (NIRS) and positron emission tomography (PET) with [¹⁸F]2FA, an α4β2 nAchR agonistic tracer (Okada et al., 2013).
Methods: The subjects were 11 healthy old and 11 AD patients. Task-induced CBF changes measured by NIRS were used as covariates. We calculated mean oxygenated hemoglobin (Δ[oxy-Hb]) values during the three periods (pre-task, the first half period, and second half period of the task) and compared them between groups. Statistical parametric mapping (SPM) was used in correlation analyses between brain [¹⁸F]2FA binding and regional Δ[oxy-Hb] levels.
Results: The two-way repeated measures ANOVA revealed significant interaction in channels 8 and 11 over the frontopolar region. SPM showed positive correlations between the Δ[oxy-Hb] levels during the task periods and [¹⁸F]2FA binding in the prefrontal region. In addition, Δ[oxy-Hb] levels in channels 2/4/5/8/10/12 that were significantly higher in HC than AD correlated positively with [¹⁸F]2FA binding in the precuneus region and right hippocampus.
Discussion: While the α4β2 nAchR activity in the PFC is associated with task-related brain activation as suggested previously, brain activation during the pre-task period might be related to the α4β2 nAchR function in the hippocampus and precuneus. The limbic α4β2 nAchR activity may be implicated in a future cognitive brain activity.