Uncovering Neuroanatomical Networks Responsible for Abnormal Eating Behavior in Frontotemporal Dementia

Magnetic resonance imaging (MRI) is a powerful tool that allowsus tonotonlyassessatrophicpatternsassociatedwithdisease but to start to unravel the complex associations between regional tissue loss and specific clinical symptoms. Patterns of atrophy associated with frontotemporal dementia (FTD) and its clinical variants have beenwell described and studies have begun to demonstrate that different behavioral symptoms observed across the FTD spectrum have different anatomical loci.1-6 Changes inone’s eatingbehavior is a behavioral feature that is particularly hard tomeasure and, hence, to studyaccuratelywithneuroimaging.Thiscould involvethetendency toovereator cramfood in themouth, indiscriminateeating, oral exploration of inanimate objects, increased selectivity in food choices, or a preference for sweet foods.7 These behaviors are typically best capturedwith caregiver questionnaires sincea lossof insight results inanunderestimationof the presence and severity of the behaviors by the patient. These questionnairesarenotperfect,however,andare limitedbyproblemswith overestimation or underestimation. In addition, the reduced quantitative scale often inherent to these questionnaires (eg,4-point scaleofnormal,mild,moderate, severe) can alsomake neuroimaging analyses difficult. In this issue of JAMA Neurology, Ahmed and colleagues8 aimed to overcome these difficulties by performing prospective well-controlled experiments to assess caloric intake and sucrose preference in patients with FTD, with the additional aimof assessingMRI correlates of performanceon these tests. An ad libitum test meal was used to assess caloric intake and an experiment involving tasting of desserts of varying sugar content was used to assess sucrose preference. These experimentswereperformed in 19patientswith thebehavioral variant of FTD (bvFTD) and 15 patients with semantic dementia (SD), aswell as in2control groupsconsistingof 15patientswith Alzheimer dementia and 25 healthy normal controls. All participants alsounderwent a3-TMRI.Theauthors found that caloric intake was only increased in the patients with bvFTD, while an increasedpreference for the sweetest dessertwasobserved in both bvFTD and SD. This increased preference for the sweetest dessert was not due to difficulty in perceiving sweetness since all groups could correctlyperceivewhichdesert was the sweetest. The MRI analysis was performed using voxel-basedmorphometryandvoxelwisegeneral linearmodel statistics to assess correlationsbetweenperformanceon these 2 tests and gray matter volume. A large number of overlapping regionswere found tocorrelatewithperformanceonboth tests.Within thebvFTDgroup, increasedcaloric intakewasassociatedwith regionsof loss extending fromthe temporal lobe (including inferior andmiddle temporal gyri and fusiform) to theoccipital lobe, aswell as the thalamus,hippocampus,parahippocampal gyrus, cingulate cortex, and cerebellum, particularly in the right hemisphere. These temporal regions and occipital lobe were also found to correlate with caloric intake in SD, although this analysis also identified a number of frontal regions, including the orbitofrontal cortex, and was more predominantly left sided. The correlation analysis for sucrose preference was performed across patients with bvFTD Related article page 282 Editorial Opinion