Rebekah M Ahmed1, Muireann Irish2, Elana Henning3, Nadene Dermody4, Lauren Bartley4, Matthew C Kiernan5, Olivier Piguet2, Sadaf Farooqi3, John R Hodges2. 1. Neuroscience Research Australia, Sydney2University of New South Wales, Sydney, Australia3Australian Research Council Centre of Excellence in Cognition and Its Disorders, University of New South Wales, Sydney, Australia4Brain and Mind Centre, Sydney Medica. 2. Neuroscience Research Australia, Sydney2University of New South Wales, Sydney, Australia3Australian Research Council Centre of Excellence in Cognition and Its Disorders, University of New South Wales, Sydney, Australia. 3. University of Cambridge Metabolic Research Laboratories and National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, United Kingdom. 4. Neuroscience Research Australia, Sydney. 5. Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
Abstract
IMPORTANCE: Abnormal eating behaviors are common in patients with frontotemporal dementia (FTD), yet their exact prevalence, severity, and underlying biological mechanisms are not understood. OBJECTIVE: To define the severity of abnormal eating behavior and sucrose preference and their neural correlates in patients with behavioral variant FTD (bvFTD) and semantic dementia. DESIGN, SETTING, AND PARTICIPANTS: Forty-nine patients with dementia (19 with bvFTD, 15 with semantic dementia, and 15 with Alzheimer disease) were recruited, and their eating behavior was compared with that of 25 healthy controls. The study was conducted from November 1, 2013, through May 31, 2015, and data analyzed from June 1 to August 31, 2015. MAIN OUTCOMES AND MEASURES: Patients participated in an ad libitum breakfast test meal, and their total caloric intake and food preferences were measured. Changes in eating behavior were also measured using the Appetite and Eating Habits Questionnaire (APEHQ) and the Cambridge Behavioral Inventory (CBI). Sucrose preference was tested by measuring liking ratings of 3 desserts of varying sucrose content (A: 26%, B: 39%, C: 60%). Voxel-based morphometry analysis of whole-brain 3-T high-resolution brain magnetic resonance imaging was used to determine the gray matter density changes across groups and their relations to eating behaviors. RESULTS: Mean (SD) ages of patients in all 4 groups ranged from 62 (8.3) to 66 (8.4) years. At the ad libitum breakfast test meal, all patients with bvFTD had increased total caloric intake (mean, 1344 calories) compared with the Alzheimer disease (mean, 710 calories), semantic dementia (mean, 573 calories), and control groups (mean, 603 calories) (P < .001). Patients with bvFTD and semantic dementia had a strong sucrose preference compared with the other groups. Increased caloric intake correlated with atrophy in discrete neural networks that differed between patients with bvFTD and semantic dementia but included the cingulate cortices, thalami, and cerebellum in patients with bvFTD, with the addition of the orbitofrontal cortices and nucleus accumbens in patients with semantic dementia. A distributed network of neural correlates was associated with sucrose preference in patients with FTD. CONCLUSIONS AND RELEVANCE: Marked hyperphagia is restricted to bvFTD, present in all patients with this diagnosis, and supports its diagnostic value. Differing neural networks control eating behavior in patients with bvFTD and semantic dementia and are likely responsible for the differences seen, with a similar network controlling sucrose preference. These networks share structures that control cognitive-reward, autonomic, neuroendocrine, and visual modulation of eating behavior. Delineating the neural networks involved in mediating these changes in eating behavior may enable treatment of these features in patients with complex medical needs and aid in our understanding of structures that control eating behavior in patients with FTD and healthy individuals.
IMPORTANCE: Abnormal eating behaviors are common in patients with frontotemporal dementia (FTD), yet their exact prevalence, severity, and underlying biological mechanisms are not understood. OBJECTIVE: To define the severity of abnormal eating behavior and sucrose preference and their neural correlates in patients with behavioral variant FTD (bvFTD) and semantic dementia. DESIGN, SETTING, AND PARTICIPANTS: Forty-nine patients with dementia (19 with bvFTD, 15 with semantic dementia, and 15 with Alzheimer disease) were recruited, and their eating behavior was compared with that of 25 healthy controls. The study was conducted from November 1, 2013, through May 31, 2015, and data analyzed from June 1 to August 31, 2015. MAIN OUTCOMES AND MEASURES: Patients participated in an ad libitum breakfast test meal, and their total caloric intake and food preferences were measured. Changes in eating behavior were also measured using the Appetite and Eating Habits Questionnaire (APEHQ) and the Cambridge Behavioral Inventory (CBI). Sucrose preference was tested by measuring liking ratings of 3 desserts of varying sucrose content (A: 26%, B: 39%, C: 60%). Voxel-based morphometry analysis of whole-brain 3-T high-resolution brain magnetic resonance imaging was used to determine the gray matter density changes across groups and their relations to eating behaviors. RESULTS: Mean (SD) ages of patients in all 4 groups ranged from 62 (8.3) to 66 (8.4) years. At the ad libitum breakfast test meal, all patients with bvFTD had increased total caloric intake (mean, 1344 calories) compared with the Alzheimer disease (mean, 710 calories), semantic dementia (mean, 573 calories), and control groups (mean, 603 calories) (P < .001). Patients with bvFTD and semantic dementia had a strong sucrose preference compared with the other groups. Increased caloric intake correlated with atrophy in discrete neural networks that differed between patients with bvFTD and semantic dementia but included the cingulate cortices, thalami, and cerebellum in patients with bvFTD, with the addition of the orbitofrontal cortices and nucleus accumbens in patients with semantic dementia. A distributed network of neural correlates was associated with sucrose preference in patients with FTD. CONCLUSIONS AND RELEVANCE: Marked hyperphagia is restricted to bvFTD, present in all patients with this diagnosis, and supports its diagnostic value. Differing neural networks control eating behavior in patients with bvFTD and semantic dementia and are likely responsible for the differences seen, with a similar network controlling sucrose preference. These networks share structures that control cognitive-reward, autonomic, neuroendocrine, and visual modulation of eating behavior. Delineating the neural networks involved in mediating these changes in eating behavior may enable treatment of these features in patients with complex medical needs and aid in our understanding of structures that control eating behavior in patients with FTD and healthy individuals.
Authors: Rebekah M Ahmed; Yazi D Ke; Steve Vucic; Lars M Ittner; William Seeley; John R Hodges; Olivier Piguet; Glenda Halliday; Matthew C Kiernan Journal: Nat Rev Neurol Date: 2018-03-23 Impact factor: 42.937
Authors: Rebekah M Ahmed; Nga Yan Tse; Yu Chen; Elana Henning; John R Hodges; Matthew C Kiernan; Muireann Irish; I Sadaf Farooqi; Olivier Piguet Journal: Ann Clin Transl Neurol Date: 2021-05-11 Impact factor: 4.511
Authors: Jet M J Vonk; Valentina Borghesani; Giovanni Battistella; Kyan Younes; Jessica DeLeon; Ariane Welch; H Isabel Hubbard; Zachary A Miller; Bruce L Miller; Maria Luisa Gorno-Tempini Journal: Aphasiology Date: 2019-09-04 Impact factor: 2.773
Authors: Ziqiang Lin; Eugene Kim; Mohi Ahmed; Gang Han; Camilla Simmons; Yushi Redhead; Jack Bartlett; Luis Emiliano Pena Altamira; Isobel Callaghan; Matthew A White; Nisha Singh; Stephen Sawiak; Tara Spires-Jones; Anthony C Vernon; Michael P Coleman; Jeremy Green; Christopher Henstridge; Jeffrey S Davies; Diana Cash; Jemeen Sreedharan Journal: Brain Commun Date: 2021-05-27
Authors: Yuriko Katsumata; Erin L Abner; Shama Karanth; Merilee A Teylan; Charles N Mock; Matthew D Cykowski; Edward B Lee; Kevin L Boehme; Shubhabrata Mukherjee; John S K Kauwe; Richard J Kryscio; Frederick A Schmitt; David W Fardo; Peter T Nelson Journal: Acta Neuropathol Date: 2020-08-14 Impact factor: 17.088