Apathy in frontotemporal dementia is related to medial prefrontal atrophy and is independent of executive dysfunction
Abstract
Introduction Apathy is the most common neuropsychiatric syndrome in behavioral variant frontotemporal dementia (bvFTD), and encompasses cognitive, behavioral and affective symptoms. The neural basis of apathy in bvFTD is not completely understood. Previous neuroimaging studies have poorly considered executive impairment and dementia severity as possible confounding factors. Herein we investigated the neural basis of apathy in bvFTD through structural neuroimaging taking into account these factors.Methods We included patients with probable bvFTD (n = 21) and cognitively healthy controls (HC, n = 22). Participants were matched for age, sex and schooling. All subjects underwent a thorough neuropsychological examination, including tests for executive functions and social cognition. Apathy was assessed with the Starkstein Apathy Scale (SAS). All subjects underwent 3T brain MRI. We investigated correlations between SAS scores and gray matter atrophy within the bvFTD group. Executive function (Frontal Assessment Battery) and disease severity were considered as covariates in neuroimaging analyses.Results Compared to HC, bvFTD patients had lower scores on global cognitive efficiency, executive functions and social cognition. All bvFTD had clinically relevant apathy (scores greater than 14 in the SAS). Performance in executive function tests did not correlate with apathy scores. The severity of apathy was negatively correlated with gray matter volumes in midline prefrontal regions, namely orbitofrontal cortex and both anterior and dorsal regions of cingulate cortex.Conclusions Apathy in bvFTD is related to a specific network of prefrontal cortical areas critically involved in effort-based behavior for rewards and appears to be independent of executive dysfunction.
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The FTD finding may be uniquely related to high rates of neuropsychiatric symptoms such as apathy consistently observed in FTD patients.
“This finding may also be uniquely related to the high rates of neuropsychiatric symptoms such as apathy consistently observed in FTD patients, particularly since neuroimaging studies previously related such behavioral changes to mPFC‐specific gray matter atrophy. 59 , 60 , 61”
From High vulnerability of medial prefrontal pyramidal neurons in post-stroke, vascular, Alzheimer's disease, and aging-related dementias (2026) · cites this paper as [61]
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- Authors
- Gonçalves, S. D. A. B., Caramelli, P., Mariano, L. I., Guimarães, H. C., Gambogi, L. B., Resende, E. D. P. F., Teixeira, A. L., & de Souza, L. C.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 1737
- Pages
- 146799
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W3011817232
- Cited by
- 29
- References
- 47
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 9 · 2022: 6 · 2021: 6 · 2020: 1
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of East Anglia
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (402853/2012-1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- apathy, behavioral variant frontotemporal dementia, medial prefrontal cortex, gray matter atrophy, executive dysfunction, orbitofrontal cortex, cingulate cortex, neuropsychiatric symptoms, reward processing, disease severity
- MeSH terms
- Aged, Aged, 80 and over, Atrophy, Brain, Brazil, Cerebral Cortex, Cognition, Female, Gyrus Cinguli, Humans, Male, Middle Aged, Neuropsychological Tests, Prefrontal Cortex, Executive Function, Frontotemporal Dementia, Apathy, Gray Matter
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