Altered Brain Serotonin Transporter and Associated Glucose Metabolism in Alzheimer Disease
Open Access
- 17 July 2009
- journal article
- research article
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 50 (8), 1260-1266
- https://doi.org/10.2967/jnumed.109.063008
Abstract
Whether preclinical depression is one of the pathophysiologic features of Alzheimer disease (AD) has been under debate. In vivo molecular imaging helps clarify this kind of issue. Here, we examined in vivo changes in the brain serotoninergic system and glucose metabolism by scanning early- to moderate-stage AD patients with and without depression using PET with a radiotracer for the serotonin transporter, 11C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl) benzonitrile (DASB), and a metabolic marker, 18F-FDG. Methods: Fifteen AD patients (8 nondepressed and 7 depressed) and 10 healthy subjects participated. All participants underwent 3-dimensional MRI and quantitative 11C-DASB PET measurements, followed by 18F-FDG PET scans in the AD group. Region-of-interest analysis was used to examine changes in 11C-DASB binding potential estimated quantitatively by the Logan plot method in the serotonergic projection region. In addition, statistical parametric mapping was used to examine whether glucose metabolism in any brain region correlated with levels of 11C-DASB binding in the dense serotonergic projection region (striatum) in AD. Results: Psychologic evaluation showed that general cognitive function (Mini-Mental State Examination) was similar between the 2 AD subgroups. Striatal 11C-DASB binding was significantly lower in AD patients, irrespective of depression, than in healthy controls (P < 0.05, corrected), and 11C-DASB binding in other dense projection areas decreased significantly in the depressive group, compared with the control group. The 11C-DASB binding potential levels in the subcortical serotonergic projection region correlated negatively with depression score (Spearman correlation, P < 0.01) but not with dementia score. Statistical parametric mapping correlation analysis showed that glucose metabolism in the right dorsolateral prefrontal cortex was positively associated with the level of striatal 11C-DASB binding in AD. Conclusion: The significant reduction in 11C-DASB binding in nondepressed AD patients suggests that presynaptic serotonergic function is altered before the development of psychiatric problems such as depression in AD. The depressive AD group showed greater and broader reductions in binding, suggesting that a greater loss of serotonergic function relates to more severe psychiatric symptoms in the disease. This serotonergic dysfunction may affect the activity of the right dorsolateral prefrontal cortex, a higher center of cognition and emotion in AD.Keywords
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