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

Abstract

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.

Lipids, apolipoproteins, and prognosis of amyotrophic lateral sclerosis

“…Several studies using diverse study populations have been conducted to examine the associations of blood lipids with the survival of patients with ALS. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] While some of the studies reported that higher lipid levels were indicative of longer survival after ALS diagnosis, [19][20][21] which is in line with the present findings, other studies reported a null association between lipids and ALS survival after multivariable adjustments. [10][11][12]14,15 The notable discrepancies among these studies may be attributable to the different study designs used, the varying timing of lipids measurement, and the choice of multivariable adjustments.…”

“…[10][11][12]14,15 The notable discrepancies among these studies may be attributable to the different study designs used, the varying timing of lipids measurement, and the choice of multivariable adjustments. For example, most studies recruited patients with ALS from neurology clinics for 2 distinct purposes, namely to investigate the putative risk factors for ALS using a case-control design 9,10,12,18,19,21 or to identify and evaluate potential predictive factors for the prognosis of ALS using a prospective cohort design. 11,[13][14][15]17,20 In the case-control design settings, it is relatively common that not only incident cases but also prevalent cases of ALS were recruited.…”

“…Most of the previous studies reported a significantly improved survival of ALS diagnosis in relation to a higher level of TG, TC, LDL-C, or LDL-C/HDL-C ratio in the univariable models (e.g., nonparametric Kaplan-Meier survival curve). 9,[11][12][13][14][15][17][18][19][20][21] However, several of these studies reported that these associations diminished or disappeared after further controlling for other prognostic indicators of ALS, and the timing of the measurements of such covariables is sometimes unclear. 12,14,15 Although it is justifiable to adjust for such covariables measured at the same time as lipids, as we did in the present study, adjustment of these variables measured later during the disease process is likely overadjustment.…”

“…8 The potential role of lipids on ALS prognosis has also been studied, however with largely conflicting results. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] We summarize findings of the existing studies in table 1. No study has, on the other hand, examined the association of ApoB or ApoAI with ALS prognosis, however.…”

Paradox of amyotrophic lateral sclerosis and energy metabolism

“…Disentangling pathogenic pathways from compensatory responses will be challenging in future studies as it seems likely that the body tries to adapt to the imbalance of increased energy metabolism by rewiring hypothalamic neural circuits leading to increased food intake 13. An increase in food and fat intake is able to secondarily affect blood lipid levels,14 which in turn have been associated with improved survival 15. As such, it seems likely that ALS may provide an ideal model to study the interaction between energy metabolism, food intake, neurodegeneration and the adaptive mechanisms that try to preserve function.…”