Altered phobic reactions in frontotemporal dementia: A behavioural and neuroanatomical analysis

Jiménez, Daniel; Bond, Rebecca L.; Requena-Komuro, Maï-Carmen; Sivasathiaseelan, Harri; Marshall, Charles R.; Russell, Lucy L.; Greaves, Caroline; Moore, Katrina; Woollacott, Ione O.C.; Shafei, Rachelle; Hardy, Chris; Rohrer, Jonathan D.; Warren, Jason D.

doi:10.1016/j.cortex.2020.05.016

Cited by 4 publications

(2 citation statements)

References 72 publications

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“…Changes in sensory behaviour (Bathgate et al, 2001; Fletcher et al, 2015) include reduced responsiveness to pain, which may lead to injury and burns, exaggerated response to innocuous stimuli such as light touch and altered response to heat and cold. Hypochondriasis (Snowden et al, 1996) and phobic responses (Jimenez et al, 2020) may occur.…”

Section: Behavioural and Cognitive Characteristics Of Bvftdmentioning

confidence: 99%

Changing perspectives on frontotemporal dementia: A review

Snowden

2022

Journal of Neuropsychology

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This article examines the evolution in understanding of frontotemporal dementia (FTD) during the last four decades. A central theme is the recognition of heterogeneity. Originally construed as a disorder of behaviour and executive impairment, FTD is now known also to be associated with alterations in language, conceptual knowledge and praxis. An absence of neurological signs is the hallmark of many FTD patients, but there is also an established association with motor neurone disease (MND), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). FTD is commonly defined as an early onset dementia, yet about a quarter of patients present after the age of 65. The underlying pathological protein is tau, TDP-43 or more rarely fused-in-sarcoma (FUS). Distinct genetic mutations have been identified in familial FTD. There are predictable relationships between clinical phenotype, pathological substrate and genetic mutation. For example, a circumscribed semantic disorder predicts TDP-43 pathology, and speech or limb apraxia tau pathology. The co-occurrence of MND predicts TDP-43 pathology, and PSP and CBD tau pathology. FUS pathology is associated with very youthful onset, stereotyped behaviours and caudate atrophy. Non-fluent aphasia is linked to progranulin (GRN) mutations and MND and psychosis to repeat expansions in the C9orf72 gene. Despite striking worldwide consensus in findings there remain some issues of contention, largely related to the classification of FTD and its sub-variants. Understanding the diverse nature of FTD is crucial for effective diagnosis, management and the development of targeted therapies.

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Section: Behavioural and Cognitive Characteristics Of Bvftdmentioning

confidence: 99%

Changing perspectives on frontotemporal dementia: A review

Snowden

2022

Journal of Neuropsychology

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“…Firstly, there is strong genetic susceptibility to both PD and AD [14]. Secondly, observational studies have found that AD patients are often comorbid with PD, phobias, and even anxiety, and that the quality of life of patients with these comorbidities is severely affected [15][16][17]. In contrast, patients with PD scored worse in all cognitive areas, and they performed worse in memory tasks [18].…”

Section: Introductionmentioning

confidence: 99%

A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis

Tian,

Ye,

Qiao

et al. 2024

BMC Psychiatry

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Background Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization. Methods Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests. Results The Cochran’s Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results. Conclusion This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.

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The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate

Chokesuwattanaskul

Jiang

Bond

et al. 2023

Brain Communications

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Abnormal reward processing is a hallmark of neurodegenerative diseases, most strikingly in frontotemporal dementia. However, the phenotypic repertoire and neuroanatomical substrates of abnormal reward behaviour in these diseases remain incompletely characterised and poorly understood. Here we addressed these issues in a large, intensively phenotyped patient cohort representing all major syndromes of sporadic frontotemporal dementia and Alzheimer’s disease. We studied 27 patients with behavioural variant frontotemporal dementia, 58 with primary progressive aphasia (22 semantic variant, 24 nonfluent/agrammatic variant, 12 logopenic) and 34 with typical amnestic Alzheimer’s disease, in relation to 42 healthy older individuals. Changes in behavioural responsiveness were assessed for canonical primary rewards (appetite, sweet tooth, sexual activity) and non-primary rewards (music, religion, art, colours), using a semi-structured survey completed by patients’ primary caregivers. Changes in more general socio-emotional behaviours were also recorded. We applied multiple correspondence analysis and k-means clustering to map relationships between hedonic domains and extract core factors defining aberrant hedonic phenotypes. Neuroanatomical associations were assessed using voxel-based morphometry of brain MRI images across the combined patient cohort. Altered (increased and/or decreased) reward responsiveness was exhibited by most patients in the behavioural and semantic variants of frontotemporal dementia and around two-thirds of patients in other dementia groups, significantly (p < 0.05) more frequently than in healthy controls. While food-directed changes were most prevalent across the patient cohort, behavioural changes directed toward non-primary rewards occurred significantly more frequently (p<0.05) in the behavioural and semantic variants of frontotemporal dementia than in other patient groups. Hedonic behavioural changes across the patient cohort were underpinned by two principal factors: a ‘gating’ factor determining the emergence of altered reward behaviour, and a ‘modulatory’ factor determining how that behaviour is directed. These factors were expressed jointly in a set of four core, trans-diagnostic and multimodal hedonic phenotypes: ‘reward-seeking’, ‘reward-restricted’, ‘eating-predominant’ and ‘control-like’ - variably represented across the cohort and associated with more pervasive socio-emotional behavioural abnormalities. The principal gating factor was associated (p < 0.05 after correction for multiple voxel-wise comparisons over the whole brain) with a common profile of grey matter atrophy in anterior cingulate, bilateral temporal poles, right middle frontal and fusiform gyri: the cortical circuitry that mediates behavioural salience and semantic and affective appraisal of sensory stimuli. Our findings define a multi-domain phenotypic architecture for aberrant reward behaviours in major dementias, with novel implications for the neurobiological understanding and clinical management of these diseases.

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Altered phobic reactions in frontotemporal dementia: A behavioural and neuroanatomical analysis

Cited by 4 publications

References 72 publications

Changing perspectives on frontotemporal dementia: A review

Changing perspectives on frontotemporal dementia: A review

A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis

The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate

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