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Allostatic-interoception network disruption and neuropsychiatric features in neurodegeneration

Poster No:

249

Submission Type:

Late-Breaking Abstract Submission

Authors:

Jessica Hazelton¹^,2^,3, Gabriel Della Bella⁴, Hernan Hernandez¹, Florencia Altschuler², Dante Sebastián Galván Rial⁴^,1, Pablo Barttfeld⁴^,1, Sophie Matis⁵, Raul Gonzalez Gomez⁶, Elisa Resende⁷^,8, Hernando Santamaría-García⁹^,10, Christopher Morrow¹¹, Chiadi Onyike¹¹, Olivier Piguet³, Ramon Landin-Romero¹², Agustín Ibáñez¹^,8^,13^,2

Institutions:

¹Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Santiago, Chile, ²Cognitive Neuroscience Center (CNC), Universidad de San Andres, Buenos Aires, Argentina, ³The University of Sydney, Brain and Mind Centre, School of Psychology, Sydney, Australia, ⁴Universidad Nacional de Córdoba, Córdoba, Argentina, ⁵The University of Sydney, Sydney, Australia, ⁶Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile, ⁷Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil, ⁸Global Brain Health Institute (GBHI), University of California San Francisco (UCSF), California, United States, United States, ⁹Pontificia Universidad Javeriana, PhD program of Neuroscience, Bogotá, Colombia, ¹⁰Global Brain Health Institute (GBHI), Trinity College Dublin, California, United States, United States, ¹¹Johns Hopkins University School of Medicine, Baltimore, United States, ¹²The University of Sydney, School of Health Sciences, Sydney, Australia, ¹³Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland, Ireland

First Author:

Jessica Hazelton, Dr
Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez|Cognitive Neuroscience Center (CNC), Universidad de San Andres|The University of Sydney, Brain and Mind Centre, School of Psychology
Santiago, Chile|Buenos Aires, Argentina|Sydney, Australia

Co-Author(s):

Gabriel Della Bella
Universidad Nacional de Córdoba
Córdoba, Argentina

Hernan Hernandez, Dr
Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez
Santiago, Chile

Florencia Altschuler
Cognitive Neuroscience Center (CNC), Universidad de San Andres
Buenos Aires, Argentina

Dante Sebastián Galván Rial
Universidad Nacional de Córdoba|Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez
Córdoba, Argentina|Santiago, Chile

Pablo Barttfeld, PhD
Universidad Nacional de Córdoba|Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez
Córdoba, Argentina|Santiago, Chile

Sophie Matis
The University of Sydney
Sydney, Australia

Raul Gonzalez Gomez, PhD
Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez
Santiago, Chile

Elisa Resende, MD, PhD
Universidade Federal de Minas Gerais|Global Brain Health Institute (GBHI), University of California San Francisco (UCSF)
Belo Horizonte, Minas Gerais, Brazil|California, United States, United States

Hernando Santamaría-García, MD, PhD
Pontificia Universidad Javeriana, PhD program of Neuroscience|Global Brain Health Institute (GBHI), Trinity College Dublin
Bogotá, Colombia|California, United States, United States

Christopher Morrow, MD, PhD
Johns Hopkins University School of Medicine
Baltimore, United States

Chiadi Onyike, MD, PhD
Johns Hopkins University School of Medicine
Baltimore, United States

Olivier Piguet
The University of Sydney, Brain and Mind Centre, School of Psychology
Sydney, Australia

Ramon Landin-Romero
The University of Sydney, School of Health Sciences
Sydney, Australia

Agustín Ibáñez
Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez|Global Brain Health Institute (GBHI), University of California San Francisco (UCSF)|Global Brain Health Institute (GBHI), Trinity College Dublin|Cognitive Neuroscience Center (CNC), Universidad de San Andres
Santiago, Chile|California, United States, United States|Dublin, Ireland, Ireland|Buenos Aires, Argentina

Introduction:

Neuropsychiatric symptoms, such as apathy, disinhibition, eating changes, delusions, hallucinations, agitation, depression, anxiety, and sleep disturbances, are common in Alzheimer's disease (AD) and frontotemporal dementia (FTD). Allostatic-interoception refers to the sensing and anticipation of cues arising from within the body and is underpinned by the allostatic-interoceptive network (AIN). It is currently unknown how structural and functional changes within the allostatic-interoceptive network relate to neuropsychiatric symptoms in neurodegenerative disorders.

Methods:

This international, multi-centre study included 9321 participants (2030 AD patients, 2664 FTD patients, 858 Mild Cognitive Impairment MCI) patients, and 3769 healthy controls) from ReDLat, ALLFTD, ADNI, ARWIBO, 4RTNI, NIFD, and Frontier Databases.
Neuropsychiatric symptoms were measured using the informant-based Neuropsychiatric Inventory (NPI). Higher scores represent more severe neuropsychiatric symptoms. Exploratory factor analysis was used to identify factors within the neuropsychiatric inventory across the cohort. The association of NPI factors with structural and functional connectivity within the AIN was evaluated, controlling for age, sex, education, country, and scanner.

Results:

We identified four distinct factors within the NPI across the cohort: 1) Apathy-Disinhibition-Eating-Aberrant motor behavior; 2) Delusions-Hallucinations; 3) Agitation-Irritability; 4) Depression-Elation-Sleep disturbances. In all neurodegenerative disease combined, greater severity across all NPI factors was associated with reduced structural integrity within the AIN, including the insula, anterior cingulate cortex, midcingulate cortex, orbitofrontal cortex, amygdala hippocampus, parahippocampus, and thalamus (pFWE < .001). Hypoconnectivity associated with NPI factors was also observed within the AIN network, including between the insula, anterior cingulate cortex, and mid cingulate cortex (pFDR <.001). This pattern across factors was also observed within behavioral variant frontotemporal dementia (bvFTD). In AD, however, greater severity in NPI factors was associated with circumscribed atrophy within the hippocampus. amygdala, and thalamus. Further, in contrast to bvFTD, hyperconnectivity associated with NPI factors 3 and 4 within the AIN, including anterior cingulate cortex, mid cingulate cortex, and insula.

Conclusions:

We provide evidence linking neuropsychiatric features commonly observed in neurodegeneration, and particularly bvFTD, to multimodal neural dysfunction within the allostatic-interoceptive network. This work suggests that altered AIN function may represent a neurobiological mechanism underlying observed clinical symptoms. This finding suggests that difficulties attending, regulating, and responding to the internal physiological condition of the body may lead to increased neuropsychiatric symptomatology in neurodegeneration, and may in part explain the clinical overlap with psychiatric illnesses. This work contributes to our theoretical understanding of allostatic-interoception dysregulation and supports synergistic models of brain health and disease.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ¹

Emotion, Motivation and Social Neuroscience:

Social Neuroscience Other

Modeling and Analysis Methods:

fMRI Connectivity and Network Modeling

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Subcortical Structures

Novel Imaging Acquisition Methods:

Multi-Modal Imaging ²

Keywords:

Cognition

Degenerative Disease

FUNCTIONAL MRI

Psychiatric

STRUCTURAL MRI

Sub-Cortical

Thalamus

Other - Allostatic-Interoception

^1|2Indicates the priority used for review

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