Lipid Metabolism and Survival Across the Frontotemporal Dementia-Amyotrophic Lateral Sclerosis Spectrum: Relationships to Eating Behavior and Cognition

Article type: Research Article

Authors: Ahmed, Rebekah M.^{a; b; c; *} | Highton-Williamson, Elizabeth^a | Caga, Jashelle^a | Thornton, Nicolette^a | Ramsey, Eleanor^a | Zoing, Margaret^a | Kim, Woojin Scott^a | Halliday, Glenda M.^{a; d} | Piguet, Olivier^{b; d; e} | Hodges, John R.^{a; b; d} | Farooqi, I. Sadaf^f | Kiernan, Matthew C.^{a; c}

Affiliations: [a] The University of Sydney, Brain and Mind Centre and Sydney Medical School, Sydney, Australia | [b] ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia | [c] Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia | [d] Neuroscience Research Australia and the University of NSW, Faculty of Medicine, Sydney, Australia | [e] The University of Sydney, School of Psychology and Brain and Mind Centre, Sydney, Australia | [f] University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

Correspondence: [*] Correspondence to: Rebekah M. Ahmed, MBBS, PhD, ForeFront Clinic, Brain and Mind Centre, 94 Mallett St Camperdown, NSW, 2050, Australia. E-mail: [email protected].

Abstract: Background:Patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) exhibit changes in eating behavior that could potentially affect lipid levels. Objective:This study aimed to document changes in lipid metabolism across the ALS-FTD spectrum to identify potential relationships to eating behavior (including fat intake), cognitive change, body mass index (BMI), and effect on survival. Methods:One hundred and twenty-eight participants were recruited: 37 ALS patients, 15 ALS patients with cognitive and behavioral change (ALS-Plus), 13 ALS-FTD, 31 behavioral variant FTD, and 32 healthy controls. Fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride levels were measured and correlated to eating behavior (caloric, fat intake), cognitive change, and BMI; effect on survival was examined using cox regression analyses. Results:There was a spectrum of lipid changes from ALS to FTD with increased triglyceride (p < 0.001), total cholesterol/HDL ratio (p < 0.001), and lower HDL levels (p = 0.001) in all patient groups compared to controls. While there was no increase in total cholesterol levels, a higher cholesterol level was found to correlate with 3.25 times improved survival (p = 0.008). Triglyceride and HDL cholesterol levels correlated to fat intake, BMI, and measures of cognition and disease duration. Conclusion:A spectrum of changes in lipid metabolism has been identified in ALS-FTD, with total cholesterol levels found to potentially impact on survival. These changes were mediated by changes in fat intake, and BMI, and may also be mediated by the neurodegenerative process, offering the potential to modify these factors to slow disease progression and improve survival.

Keywords: Amyotrophic lateral sclerosis, cholesterol, eating, frontotemporal dementia, hypothalamus, metabolism,neurodegeneration, neuroendocrine

DOI: 10.3233/JAD-170660

Journal: Journal of Alzheimer's Disease, vol. 61, no. 2, pp. 773-783, 2018