Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer's Disease and Mild Cognitive Impairment.
Angela J HansonWilliam A BanksLisa F BettcherRobert PepinDaniel RafterySandi L NavarroSuzanne CraftPublished in: Metabolites (2023)
Brain glucose hypometabolism is an early sign of Alzheimer's disease (AD), and interventions which offset this deficit, such as ketogenic diets, show promise as AD therapeutics. Conversely, high-fat feeding may exacerbate AD risk. We analyzed the metabolomic profile of cerebrospinal fluid (CSF) in a pilot study of older adults who underwent saline and triglyceride (TG) infusions. Older adults (12 cognitively normal (CN), age 65.3 ± 8.1, and 9 with cognitive impairment (CI), age 70.9 ± 8.6) underwent a 5 h TG or saline infusion on different days using a random crossover design; CSF was collected at the end of infusion. Aqueous metabolites were measured using a targeted mass spectroscopy (MS) platform focusing on 215 metabolites from over 35 different metabolic pathways. Data were analyzed using MetaboAnalyst 4.0 and SAS. Of the 215 targeted metabolites, 99 were detectable in CSF. Only one metabolite significantly differed by treatment: the ketone body 3-hydroxybutyrate (HBA). Post hoc analyses showed that HBA levels were associated with age and markers of metabolic syndrome and demonstrated different correlation patterns for the two treatments. When analyzed by cognitive diagnosis group, TG-induced increases in HBA were over 3 times higher for those with cognitive impairment (change score CN +9.8 uM ± 8.3, CI +32.4 ± 7.4, p = 0.0191). Interestingly, individuals with cognitive impairment had higher HBA levels after TG infusion than those with normal cognition. These results suggest that interventions that increase plasma ketones may lead to higher brain ketones in groups at risk for AD and should be confirmed in larger intervention studies.
Keyphrases
- cognitive impairment
- mild cognitive impairment
- cerebrospinal fluid
- cognitive decline
- physical activity
- ms ms
- mass spectrometry
- metabolic syndrome
- white matter
- low dose
- randomized controlled trial
- cancer therapy
- resting state
- multiple sclerosis
- weight loss
- big data
- lymph node metastasis
- squamous cell carcinoma
- electronic health record
- uric acid
- high resolution
- cerebral ischemia
- small molecule
- diabetic rats
- blood pressure
- oxidative stress
- combination therapy
- type diabetes
- open label
- ionic liquid
- double blind
- blood brain barrier
- single molecule
- deep learning
- skeletal muscle