Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease
Open accessAbstract
Background Apathy is a common and early symptom in Alzheimer's disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions.Objective To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD.Methods Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and non-apathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates.Results At a p FWE < .05 threshold, apathetic patients had reduced connectivity between the left insula and right superior parietal cortex. Apathetic patients had also increased connectivity between the right dorsolateral prefrontal seed and the right superior parietal cortex. Patients with apathy were significantly more likely to experience other psychiatric symptoms.Conclusion Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions.
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The presence of psychiatric symptoms in patients with Alzheimer's disease is associated with alterations of brain circuitry.
“A number of studies has shown that the presence of psychiatric symptoms in patients with AD is associated with alterations of brain circuitry (37–39).”
From The impact of COVID-19 infection and enforced prolonged social isolation on neuropsychiatric symptoms in older adults with and without dementia: A review (2020) · cites this paper as [37]
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Apathy in Mild Behavioural Impairment: Associations with Cortical Thickness and Grey Matter VolumePreprint
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Fiber connectivity density in subcortical stroke patients with behavioral dysexecutive symptoms
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- Authors
- Jones, S. A., De Marco, M., Manca, R., Bell, S. M., Blackburn, D. J., Wilkinson, I. D., Soininen, H., & Venneri, A.
- Affiliations
- Sheffield Health and Social Care NHS Foundation Trust (GB)
- University of Sheffield (GB)
- University of Eastern Finland (FI)
- Corresponding author
- Venneri, Annalena
- ORCID
- Venue
- Cortex
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 119
- Pages
- 100-110
- ISSN
- 0010-9452 (ISSN-L)
- OpenAlex
- W2940140866
- Cited by
- 37
- References
- 57
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 6 · 2019: 1
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- green
- erepo.uef.fi
- Licence
- Locations
- Cortex (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by-nc-nd)
- Funders
- European Commission
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- apathy, Alzheimer's disease, functional connectivity, insula, frontal cortex, dorsolateral prefrontal cortex, superior parietal cortex, anterior cingulate cortex, amygdala, neuropsychiatric symptoms, value-based decision making, resting-state fMRI
- MeSH terms
- Alzheimer Disease, Brain, Brain Mapping, Cerebral Cortex, Female, Humans, Image Processing, Computer-Assisted, Male, Neural Pathways, Apathy
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