Abstract
Although l-carnitine alleviated white-matter lesions in an experimental study, the treatment effects of l-carnitine on white-matter microstructural damage and cognitive decline in hemodialysis patients are unknown. Using novel diffusion magnetic resonance imaging (dMRI) techniques, white-matter microstructural changes together with cognitive decline in hemodialysis patients and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent dMRI and laboratory and neuropsychological tests, which were compared across seven patients each in two groups according to duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment (NSTLC), and (2) long-term l-carnitine treatment (LTLC). Ten age- and sex-matched controls were enrolled. Compared to controls, microstructural disorders of white matter were widely detected on dMRI of patients. An autopsy study of one patient in the NSTLC group showed rarefaction of myelinated fibers in white matter. With LTLC, microstructural damage on dMRI was alleviated along with lower levels of high-sensitivity C-reactive protein and substantial increases in carnitine levels. The LTLC group showed better achievement on trail making test A, which was correlated with amelioration of disorders in some white-matter tracts. Novel dMRI tractography detected abnormalities of white-matter tracts after hemodialysis. Long-term treatment with l-carnitine might alleviate white-matter microstructural damage and cognitive impairment in hemodialysis patients.
Highlights
Correlated with the substantial increase in patients with end-stage renal disease due to diabetes mellitus, hypertension, and obesity, the number of patients on maintenance dialysis has risen greatly, to 284 individuals per million population worldwide [1]
The principal findings of the current study were that impairment of white-matter tracts was robustly detected in hemodialysis patients with pathological confirmation in an autopsy case, and these injuries were alleviated by treatment with long-term L-carnitine treatment (LTLC), along with reduction of high-sensitivity C-reactive protein (hs-CRP) levels
Hemodialysis patients treated with LTLC displayed better performance on trail making test (TMT)-A than hemodialysis patients with no or short-term L-carnitine treatment (NSTLC), and specific white-matter tracts that contributed to the achievement of TMA-A were identified
Summary
Correlated with the substantial increase in patients with end-stage renal disease due to diabetes mellitus, hypertension, and obesity, the number of patients on maintenance dialysis has risen greatly, to 284 individuals per million population worldwide [1]. Cognitive impairment is critical in hemodialysis patients and is associated with death and dialysis withdrawal [2]. A previous large-scale cohort study of hemodialysis patients documented the prevalence of diagnosed dementia as 4%, whereas several studies investigated cognitive function tests of hemodialysis patients, showing cognitive impairment in as many as 87% [2,3,4]. There may be more undiagnosed or covert vascular dementia in hemodialysis patients than expected. Using DTI, the association of white-matter fiber tract disorders with cognitive decline has been reported in vascular dementia, as well as small vessel diseases in hemodialysis patients [8,9,10,11], no evidence is currently available for the analysis of white-matter fiber tracts using msdMRI techniques
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