Molecular imaging of serotonin degeneration in mild cognitive impairment

Gwenn Smith, Frederick Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin J. Sodums, Christopher M. Marano, Cynthia Munro, Jason Brandt, Michael A Kraut, Yun Zhou, Dean Foster Wong, Clifford I. Workman

Research output: Contribution to journalArticle

Abstract

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6 ± 6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2 ± 7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic areas typically affected by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum and thalamus that are relatively spared in Alzheimer's disease. The reduction of the serotonin transporter in mild cognitive impairment was greater than grey matter atrophy or reductions in regional cerebral blood flow compared to controls. Lower cortical serotonin transporters were associated with worse performance on tests of auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. The serotonin system may represent an important target for prevention and treatment of MCI, particularly the post-synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as presynaptic aspects of the serotonin system, as indicated by the observation of lower serotonin transporters in MCI relative to healthy controls.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalNeurobiology of Disease
Volume105
DOIs
StatePublished - Sep 1 2017

Fingerprint

Molecular Imaging
Serotonin Plasma Membrane Transport Proteins
Serotonin
Cerebrovascular Circulation
Regional Blood Flow
Alzheimer Disease
Cognitive Dysfunction
Neurotransmitter Receptor
Raphe Nuclei
Thalamus
Amyloid
Neuroimaging
Positron-Emission Tomography
Atrophy
Magnetic Resonance Imaging
Observation
Pathology

Keywords

  • Aging
  • Mild cognitive impairment
  • Positron emission tomography (PET)
  • Serotonin transporter

ASJC Scopus subject areas

  • Neurology

Cite this

Molecular imaging of serotonin degeneration in mild cognitive impairment. / Smith, Gwenn; Barrett, Frederick; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J.; Marano, Christopher M.; Munro, Cynthia; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean Foster; Workman, Clifford I.

In: Neurobiology of Disease, Vol. 105, 01.09.2017, p. 33-41.

Research output: Contribution to journalArticle

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