Biological bases of eating behavior disturbance in frontotemporal dementia

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.This work was supported by funding to Forefront, a collaborative research
group dedicated to the study of frontotemporal dementia and motor neurone disease,
from the National Health and Medical Research Council of Australia (NHMRC)
program grant (#1037746 to MK and JH) and the Australian Research Council Centre
of Excellence in Cognition and its Disorders Memory Node (#CE110001021 to OP
and JH) and other grants/sources (NHMRC project grant #1003139). We are grateful
to the research participants involved with the ForeFront research studies. RA is a
Royal Australasian College of Physicians PhD scholar and MND Australia PhD
scholar. MI is an ARC Discovery Early Career Researcher Award Fellow
Ahmed et al. (#DE130100463). OP is an NHMRC Career Development Research Fellow
(#1022684). ISF is supported by the Wellcome Trust, Medical Research Council,
European Research Council, NIHR Cambridge Biomedical Research Centre and The
Bernard Wolfe Endowment.This is the author accepted manuscript. The final version is available from American Medical Association at http://dx.doi.org/10.1001/jamaneurol.2015.4478