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Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons.

ABSTRACT: Plasmalogens are a specific type of glycerophospholipid found in especially high levels in neuronal membranes. Decreased blood and brain levels of docosahexaenoic acid (DHA) containing plasmalogens are associated with decreased cognition and neuromuscular function in humans. Administration of 1-O-alkyl-2-acylglycerol (AAG) plasmalogen precursors containing DHA at the sn-2 position dose-dependently increase blood DHA plasmalogens and are neuroprotective in animal models of neurodegeneration at doses between 10 and 50 mg/kg. We conducted an investigational clinical trial in 22 cognitively impaired persons to evaluate the effects of an escalating oral dosing regimen of DHA-AAG from 900 to 3,600 mg/day over a 4-month period on blood serum plasmalogen and non-plasmalogen phospholipids and oxidative stress biomarkers. Safety, tolerability and therapeutic effects on cognition and mobility were also evaluated. DHA plasmalogen levels increased with increasing dose and remained significantly elevated at all treatment doses and durations. DHA plasmalogen levels were positively associated with catalase activity and negatively associated with malondialdehyde (MDA) levels. DHA-AAG supplementation normalized catalase activity in persons with low baseline catalase activity, normalized MDA levels in persons with high baseline MDA levels, and normalized superoxide dismutase activity in persons with high baseline SOD activity. Cognition improved in nine participants, was unchanged in nine, and declined in four. Mobility improved in twelve, was unchanged in five and declined in four participants. Changes in cognition and mobility were statistically significant versus a random outcome. Baseline DHA-plasmalogen levels were not predictive of clinical response. DHA-AAG was well tolerated at all dosages and no adverse reactions were observed.

SUBMITTER: Goodenowe DB

PROVIDER: S-EPMC9297104 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AIM:The main purpose of the present study was to verify the feasibility of wearable inertial sensors (IMUs) in a clinical setting to screen gait and functional mobility in Italian older persons. In particular, we intended to verify the capability of IMUs to discriminate individuals with and without cognitive impairments and assess the existence of significant correlations between mobility parameters extracted by processing trunk accelerations and cognitive status. METHODS:This is a cross-sectional study performed on 213 adults aged over 65 years (mean age 77.0?±?5.4; 62% female) who underwent cognitive assessment (through Addenbrooke's Cognitive Examination Revised, ACE-R) instrumental gait analysis and the Timed Up and Go (TUG) test carried out using a wearable IMU located in the lower back. RESULTS:Individuals with cognitive impairments exhibit a peculiar gait pattern, characterized by significant reduction of speed (-?34% vs. healthy individuals), stride length (-?28%), cadence (-?9%), and increase in double support duration (+?11%). Slight, but significant changes in stance and swing phase duration were also detected. Poorer performances in presence of cognitive impairment were observed in terms of functional mobility as overall and sub-phase TUG times resulted significantly higher with respect to healthy individuals (overall time,?+?38%, sub-phases times ranging from?+?22 to?+?34%), although with some difference associated with age. The severity of mobility alterations was found moderately to strongly correlated with the ACE-R score (Spearman's rho?=?0.58 vs. gait speed, 0.54 vs. stride length, 0.66 vs. overall TUG time). CONCLUSION:The findings obtained in the present study suggest that wearable IMUs appear to be an effective solution for the clinical assessment of mobility parameters of older persons screened for cognitive impairments within a clinical setting. They may represent a useful tool for the clinician in verifying the effectiveness of interventions to alleviate the impact of mobility limitations on daily life in cognitively impaired individuals.

Project description:ImportanceThe role of amyloid in the progression of Alzheimer disease (AD) pathophysiology is of central interest to the design of randomized clinical trials. The presence of amyloid has become a prerequisite for enrollment in several secondary prevention trials for AD, yet the precise effect of elevated amyloid levels on subsequent clinical and biomarker events is less certain.ObjectiveTo explore the effect of elevated amyloid levels on subsequent changes in cognition and biomarkers.Design, setting, and participantsA total of 564 cognitively normal individuals (median age, 78 years) from the Mayo Clinic Study of Aging, a population-based longitudinal study in Olmsted County, Minnesota, with serial cognitive data were selected for this study. The data used in this study were collected from January 12, 2006, to January 9, 2014. Individuals included in this study had undergone magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (FDG-PET), and Pittsburgh Compound B (PiB) PET at baseline were not cognitively impaired at baseline and had at least 1 clinical follow-up. A subset of 286 individuals also underwent serial imaging. Elevated amyloid level was defined as a standardized uptake value ratio of greater than 1.5 on PiB PET. Associations with baseline amyloid status and baseline and longitudinal change in clinical and imaging measures were evaluated after adjusting for age and hippocampal volume. APOE4 effects were also evaluated.Main outcomes and measuresCognitive measures of memory, language, attention/executive function, visuospatial skills, PiB levels, hippocampal and ventricular volumes, and FDG-PET measures.ResultsAt baseline, 179 (31.7%) individuals with elevated amyloid levels had poorer cognition in all domains measured, reduced hippocampal volume, and greater FDG-PET hypometabolism. Elevated amyloid levels at baseline were associated with a greater rate of cognitive decline in all domains (0.04 to 0.09 z score units per year) except language and a greater rate of amyloid accumulation (1.6% per year), hippocampal atrophy (30 mm3 per year), and ventricular enlargement (565 mm3 per year). Elevated amyloid levels were also associated with an increased risk of mild cognitive impairment (hazard ratio, 2.9; 95% CI, 1.7-5.0, and hazard ratio, 1.6; 95% CI, 0.9-2.8, for PiB+ APOE4 carriers and PiB+ noncarriers, respectively, compared with PiB- noncarriers). These associations were largely independent of APOE4.Conclusions and relevanceIn persons selected from a population-based study, elevated amyloid levels at baseline were associated with worse cognition and imaging biomarkers at baseline and with greater clinical decline and neurodegeneration. These results have implications for the design of randomized clinical trials for AD.

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Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons.

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