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Abstract
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 ± 89 pg/mL) and svPPA (62 ± 81 pg/mL) compared with controls (23 ± 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.
GLOSSARY
- ACE-R=
- Addenbrooke's Cognitive Examination–Revised;
- AD=
- Alzheimer disease;
- AgRP=
- agouti-related peptide;
- APEHQ=
- Appetite and Eating Habits Questionnaire;
- BMI=
- body mass index;
- bvFTD=
- behavioral variant frontotemporal dementia;
- CBI=
- Cambridge Behavioural Inventory;
- CCK=
- cholecystokinin;
- CDR=
- Clinical Dementia Rating;
- FRS=
- Frontotemporal Dementia Rating Scale;
- FTD=
- frontotemporal dementia;
- PYY=
- peptide tyrosine tyrosine;
- svPPA=
- semantic variant primary progressive aphasia;
- TDP-43=
- TAR DNA-binding protein 43
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received March 2, 2015.
- Accepted in final form June 8, 2015.
- © 2015 American Academy of Neurology
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