Satiety-related hormonal dysregulation in behavioral variant frontotemporal dementia

Woolley, Josh; Khan, Baber; Natesan, Alamelu; Karydas, Anna; Dallman, Mary F.; Havel, Peter J.; Miller, Bruce L.; Rankin, Katherine P.

doi:10.1212/wnl.0000000000000106

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…Despite the recognized role of the hypothalamus in eating behavior, only one study has investigated the possible role of the hypothalamus in FTD and showed atrophy of the posterior hypothalamus in FTD patients [64]. Interestingly, Woolley et al [65] recently published a study showing an association between overeating and an anorexigenic hormonal profile in bvFTD patients, which is consistent with the satiety acknowledged by patients and can be interpreted as a compensatory mechanism. At late stages of the disease, these changes can evolve toward hyperorality.…”

Section: The Ftd Symptoms and Corresponding Tests In Micementioning

confidence: 90%

Evaluating Behavior in Mouse Models of the Behavioral Variant of Frontotemporal Dementia: Which Test for Which Symptom?

Vernay

Sellal²,

Frydman³

2015

Neurodegener Dis

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The behavioral variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease affecting people in their early sixties, characterized by dramatic changes in individual and social behavior. Despite the heterogeneity in the presentation of the clinical symptoms of bvFTD, some characteristic changes can be highlighted. Social disinhibition, changes in food preferences as well as loss of empathy and apathy are commonly described. This is accompanied by a characteristic and dramatic atrophy of the prefrontal cortex with the accumulation of protein aggregates in the neurons in this area. Several causative mutations in different genes have been discovered, allowing the development of transgenic animal models, especially mouse models. In mice, attention has been focused on the histopathological aspects of the pathology, but now studies are taking interest in assessing the behavioral phenotype of FTD models. Finding the right test corresponding to human symptoms is quite challenging, especially since the frontal cortex is much less developed in mice than in humans. Although challenging, the ability to detect relevant prefrontal cortex impairments in mice is crucial for therapeutic approaches. In this review, we aim to present the approaches that have been used to model the behavioral symptoms of FTD and to explore other relevant approaches to assess behavior involving the prefrontal cortex, as well as the deficits associated with FTD.

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Section: The Ftd Symptoms and Corresponding Tests In Micementioning

confidence: 90%

Evaluating Behavior in Mouse Models of the Behavioral Variant of Frontotemporal Dementia: Which Test for Which Symptom?

Vernay

Sellal²,

Frydman³

2015

Neurodegener Dis

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“…Decreased ghrelin and cortisol levels, as well as high insulin levels, have been previously reported in bvFTD. 5 Insulin levels, however, were not related to BMI, which could reflect a state of insulin resistance and metabolic change, 4 rather than a role in controlling satiety. High leptin levels were also observed in a small subset of patients with bvFTD (n 5 5) who overate.…”

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confidence: 93%

“…High leptin levels were also observed in a small subset of patients with bvFTD (n 5 5) who overate. 5 Another study failed to find significant differences in leptin levels between patients with FTD and those with AD dementia, although the authors suggested that hyperphagic females with FTD may have higher leptin levels. 23 This finding seems paradoxical to the eating behaviors seen in bvFTD, as leptin inhibits food intake.…”

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confidence: 99%

“…4 The underlying pathophysiology of these eating changes and the possibility of differences between bvFTD and svPPA have not been systematically investigated. One study 5 has suggested that low ghrelin and cortisol levels and high leptin levels observed in bvFTD represent compensatory mechanisms to the excess eating triggered by brain pathology involving the orbitofrontal cortex and the posterior hypothalamus. 6,7 The hypothalamus is involved in 2 major pathways that mediate appetite and eating behavior (figure 1): an appetite-stimulating pathway, with key peptides including ghrelin and agouti-related peptide (AgRP), and an appetitesuppressing pathway, with key peptides including leptin.…”

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confidence: 99%

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Eating behavior in frontotemporal dementia

et al. 2015

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Objective: To contrast the relationships of hormonal eating peptides and hypothalamic volumes to eating behavior and metabolic changes (body mass index [BMI]) in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA).Methods: Seventy-five patients with dementia (19 bvFTD, 26 svPPA, and 30 Alzheimer disease dementia) and 23 controls underwent fasting blood analyses of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) levels. On brain MRI anterior, posterior, and total hypothalamic volumes were measured. Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were investigated.Results: Levels of AgRP were higher in patients with bvFTD (69 6 89 pg/mL) and svPPA (62 6 81 pg/mL) compared with controls (23 6 19 pg/mL, p , 0.01). No differences were found for leptin, oxytocin, cholecystokinin, ghrelin, and PYY levels. Patients with bvFTD and svPPA had higher scores on questionnaires measuring eating behaviors. Atrophy of the posterior and total hypothalamus was observed in the bvFTD group only. Linear regression modeling revealed that leptin and AgRP levels predicted BMI. Conclusion:Eating abnormalities are multifactorial in FTD. In bvFTD, they are in part related to hypothalamic degeneration, with potential disintegration of the network connections between the hypothalamus and orbitofrontal cortex/reward pathways. In svPPA, although hypothalamic volumes are preserved, this group experiences elevated AgRP levels similar to bvFTD, which predicts BMI in both groups. This finding highlights the potential key role of AgRP in eating and metabolic changes and provides a potential target for treatment to modify disease progression. Alterations in eating behavior are one of the diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD).

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“…Appetite-regulating peptide levels in subjects with bvFTD are found to be consistent with an expected satiated state between meals [18, 32, 33]. Appetite-regulating peptide levels differ between subjects with bvFTD and healthy controls.…”

Section: Frontotemporal Lobar Degenerationmentioning

confidence: 96%

A Review: Mealtime Difficulties following Frontotemporal Lobar Degeneration

Lewis

Walterfang

Velakoulis

et al. 2018

Dement Geriatr Cogn Disord

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Background: Frontotemporal lobar degeneration (FTLD) can result in a decline in behavior, language, and motor function. Mealtime disturbances are a common and significant outcome of FTLD. Disturbances during mealtimes can arise from dysphagia or may occur secondary to behavioral changes such as rapid eating, mealtime rigidity, and altered diet preferences. Summary: Few studies have comprehensively evaluated eating behavior or dysphagia in individuals presenting with FTLD pathology despite the potential impact on medical safety and individual quality of life. Dysphagia is reported in the late stages of frontotemporal dementia and early in the motor subtypes of FTLD. The identification of dysphagia can alert individuals and medical teams to disease progression and provide insight into the nature and spread of the underlying neuropathology. Improved understanding of eating behaviors can improve individual care and may enhance diagnostic accuracy. Key Message: Aberrant eating behavior and swallowing difficulties are reported in the conditions associated with FTLD neuropathology. The consequences of mealtime disturbances include health risks associated with an increased BMI and aspiration, reduction of an individual’s independence, and an increase in caregiver stress and burden. Here we review and summarize the literature on eating behavior and swallow impairments (dysphagia) in each of the syndromes caused by FTLD.

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Satiety-related hormonal dysregulation in behavioral variant frontotemporal dementia

Abstract: Despite a tendency to overeat, patients with bvFTD have a hormonal profile that should decrease food intake. Aberrant hormone levels may represent a compensatory response to the behavioral or neuroanatomical abnormalities of bvFTD.

Cited by 30 publications

References 41 publications

Evaluating Behavior in Mouse Models of the Behavioral Variant of Frontotemporal Dementia: Which Test for Which Symptom?

Evaluating Behavior in Mouse Models of the Behavioral Variant of Frontotemporal Dementia: Which Test for Which Symptom?

Eating behavior in frontotemporal dementia

A Review: Mealtime Difficulties following Frontotemporal Lobar Degeneration

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