Neurotransmitters profile in Alzheimer's Disease patients with or without anosognosia
Poster No:
113
Submission Type:
Abstract Submission
Authors:
Daniela Ballotta1, Annalisa Chiari2, Giovanna Zamboni1, Manuela Tondelli1
Institutions:
1University of Modena and Reggio EMilia, Modena, Italy, 2Azienda Ospedaliero Universitaria di Modena, Modena, Italy
First Author:
Co-Author(s):
Introduction:
Patients with Alzheimer's Disease (AD) may be unaware of their cognitive and behavioural symptoms ("anosognosia" or "impaired self-awareness"; Pringatano, 2009) even in the early phases of the AD continuum, including the Mild Cognitive Impairment (MCI) phase. Anosognosia in these patients has significant clinical implications for their care, reduces compliance to treatment, threatens patient's safety, and increases caregiver burden (Starkstein et al., 2007). The aim of the present study was to test whether anosognosia in AD and MCI is associated with specific neurotransmitter changes, which may represent plausible therapeutic targets. The correlation between the spatial patterns of Grey Matter Volume (GMV) alterations and specific neurotransmitter systems was investigated in aware and unaware AD and MCI patients.
Methods:
Twenty-one patients with MCI and AD underwent MRI and neuropsychological assessment. Patients were categorized as aware (9 patients) or unaware (12 patients) of their cognitive impairment, according to the Anosognosia Questionnaire Dementia (Migliorelli et al., 1995). Twenty age-matched healthy controls (HC) were also recruited. Structural MRI data (T1-weighted anatomical image;170 sagittal slices; TR = 9.9 ms; TE = 4.6 ms; in plane matrix = 256 × 256; voxel size = 1 mm × 1 mm × 1 mm) were pre-processed and analysed with the Voxel Based Morphometry pipeline implemented in the Computational Anatomy Toolbox (CAT12) for SPM12 to identify grey matter atrophy in patients; then, GMV alterations of Aware and Unaware (both relative to HC) were correlated with nuclear imaging derived estimates related to several neurotransmitter systems (dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission) using the Juspace toolbox implemented in SPM12 (Dukart, 2020).
Results:
Compared to HC, GMV patterns of insular cortex, lateral and medial temporal cortices of aware patients were significantly associated with the spatial distribution of 5-HT2a receptors (r = -0.15, p < 0.001), dopamine transporter DAT (r = 0.18, p < 0.001), and mGluR5 (r = -0.23, p < 0.001). Unaware patients, relative to HC, showed widespread grey matter atrophy in lateral and medial temporal cortices, anterior insula/inferior frontal gyrus, posterior cingulate cortex/precuneus, superior frontal gyrus. This atrophy pattern was significantly associated with the spatial distribution of 5-HT1a receptors (r = -0.21, p < 0.001), D2 receptors (r = 0.16, p < 0.001), and dopamine transporter DAT (r = 0.21, p < 0.001).
Conclusions:
Our results suggest the involvement of specific neurotransmitter pathways in AD and MCI patients with or without anosognosia. Mainly, we showed that the GMV pattern of aware patients was especially correlated with brain areas with high serotonin and glutamate receptors density in healthy subjects, and low density of dopamine transporter. The GMV pattern of unaware patients, instead, was correlated with areas with low density of both dopamine transporter and dopamine receptors. Although exploratory, our findings provide novel insight into the neurotransmitters mechanisms associated with anosognosia and may have implications in clinical practice to identify new therapeutic targets aimed at reducing anosognosia.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Transmitter Systems
Novel Imaging Acquisition Methods:
Anatomical MRI
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Consciousness
Degenerative Disease
Dopamine
Neurotransmitter
RECEPTORS
Seretonin
STRUCTURAL MRI
1|2Indicates the priority used for review
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Starkstein, S. E. (2007). Insight and danger in Alzheimer's Disease. Eur. J. Neurol. 14, 455–460.
Migliorelli, R. et al. (1995) Anosognosia in Alzheimer's disease: a study of associated factors. J Neuropsychiatry Clin Neurosci, 7, 338-44.
Dukart, J. et al. (2021) JuSpace: a tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps. Hum. Brain Mapp., 42, 555–566.