Table 3.

Correlations between the changes in nicotinic binding sites in the brain assessed by PET and the RBC AChE inhibition after 3 and 12 months follow-up.

		The RBC AChE Inhibition
		3-months				12-months
		Placebo (n = 6)		Galantamine (n = 11)		Overall patients (n = 13)
11C- nicotine binding in the brain regions (%1-k2*)		r	p < 0.05	r	p < 0.05	r	p < 0.05
Cortical regions	L	−0.79	0.07	0.61	0.05	−0.47	0.1
	R	−0.66	0.17	0.73	0.009	−0.51	0.07
Overall brain regions	L	−0.86	0.03	0.67	0.02	−0.53	0.07
	R	−0.66	0.17	0.70	0.01	−0.53	0.07
Average L & R cortical		−0.76	0.09	0.70	0.05	−0.50	0.08
Average L and R overall brain regions		−0.89	0.05*	0.71	0.01	0.54	0.06
Whole brain		−0.83	0.06*	0.76	0.005	−0.60	0.03

All r-values are correlation coefficient. A negative r-value reflects an inverse association between RBC AChE inhibition and the changes in the nicotinic binding sites in the brain. It should be noted that enzyme inhibition has an inverse relation with enzyme activity. Thereby, a negative r-value among the Placebo group means positive association between activity of the enzyme and the changes in the nicotinic binding sites in the brain. Overall, the negative r-value for this group in the table most likely point toward a native biodynamic relationship, meaning that a high ACh degradation (due to low or no inhibition of AChE) might become compensated by an increase in the number of nicotinic receptors to allow neurotransmission. This is because changes in RBC AChE activity or the nicotinic binding sites in the Placebo group during the initial 3 months of study are not caused by galantamine as these patients were on placebo. In contrast, the positive r-values found between these two variables in the Galantamine group indicate that a high AChE inhibition (i.e., a consequently high level and/or long duration of action of ACh within synapses) was accompanied by an increase in the number of nicotinic receptors in the brain. This in turn suggests that such cholinergic stimulation by the drug might induce neuronal and/or synaptic remodeling that requires more ACh receptors and cholinergic enzymes, such as ChAT and AChE to be expressed in the brain as we found in the current study (see also further schematic explanations in Figure 5D). Some of these correlations are graphically illustrated in Figure 4B. k₂* values for ¹¹C-nicotine binding are exemplified in Figure 3. *p-values are based on Spearman Rank Correlation; PET, Positron emission tomography, k₂* = the binding constant. RBC AChE, Red blood cells acetylcholinesterase.