Commonalities in biomarkers and phenotypes between mild cognitive impairment and cerebral palsy: a pilot exploratory study

Abstract

Clinically, individuals with cerebral palsy (CP) experience symptoms of accelerated biological aging. Accumulative deficits in both molecular underpinnings and functions in young adults with CP can lead to premature aging, such as heart disease and mild cognitive impairment (MCI). MCI is an intermediate stage between healthy aging and dementia that normally develops at old age. Owing to their intriguingly parallel yet “inverted” disease trajectories, CP might share similar pathology and phenotypes with MCI, conferring increased risk for developing dementia at a much younger age. Thus, we examined this hypothesis by evaluating these two distinct populations (MCI= 55, CP = 72). A total of nine measures (e.g., blood biomarkers, neurocognition, Framingham Heart Study Score (FHSS) were compared between the groups. Compared to MCI, upon controlling for covariates, delta FHSS, brain-derived neurotrophic factor (BDNF) levels, and systolic blood pressure were significantly lower in CP. Intriguingly, high-sensitivity CRP, several metabolic outcomes, and neurocognitive function were similar between the two groups. This study supports a shared biological underpinning and key phenotypes between CP and MCI. Thus, we proposed a double-hit model for the development of premature aging outcomes in CP through shared biomarkers. Future longitudinal follow-up studies are warranted to examine accelerated biological aging.

Increased plasma brain-derived neurotrophic factor (BDNF) as a potential biomarker for and compensatory mechanism in mild cognitive impairment: a case-control study

“…CP had significantly lower plasma BDNF levels and high discriminative accuracy, compared to controls who were older adults without MCI. This finding concurs with our previous findings reporting decreased peripheral BDNF in CP compared to MCI [ 48 ]. In this study, we showed that after addressing the factors causing heterogeneity in plasma BDNF and removing cases with co-morbidities, the findings still hold, suggesting relative independence of plasma BDNF from psychiatric co-morbidities in CP.…”

“…The CP cross-sectional study [ 48 , 72 ] was approved by the Colorado Multiple Institutional Review Board (COMIRB Reference No: 14-0367), and registered with the clinical trial database ( https://clinicaltrials.gov/ct2/show/NCT02137005 ). The study was conducted at a clinical motion analysis laboratory at Children’s Hospital Colorado.…”

“…This hypothesized neuro-immune-stress axis [ 42 ] could be evidenced by the presence of significant associations between peripheral BDNF, with hs-CRP and DHEA-S. Worthy of note is that, apart from MCI, these biomarkers have also been implicated in MDD and GAD [ 43 – 47 ]. In addition, adults with cerebral palsy (CP) whom often have co-morbid MCI, have similarly dysregulated biomarker levels [ 48 ], particularly similar hs-CRP level and lower plasma BDNF than MCI, hence making it even more imperative to control for the clinical and laboratory heterogeneity. Considering cases with co-morbid MDD, GAD, and CP will allow a deeper understanding of the utility of these biomarkers in discriminating MCI from cognitive healthy aging.…”

Associations of Circulating Insulin-Growth Factor-1 With Cognitive Functions and Quality of Life Domains in Ambulatory Young Adults With Cerebral Palsy: A Pilot Study

“…Cerebral palsy (CP) is a lifelong condition that presents challenges at every stage of development. Evidence suggests that adults with CP are at a higher risk of developing chronic secondary health conditions associated with aging, such as diabetes, hypertension, heart diseases, and metabolic syndrome, and at a much earlier age than typically-developing adults (1)(2)(3)(4)(5). These chronic diseases are also risk factors for dementia and have been shown to be associated with mobility impairment, due to fatigue, walking inefficiency, frailty, and muscle and joint pain (6).…”

“…One important but underdiagnosed clinical condition in adults with CP is cognitive impairment (2,(9)(10)(11). Our previous study showed that a great proportion, i.e., 75%, of our adult patients with CP screened positive for cognitive impairment defined as mild cognitive impairment (MCI) (2). We thus postulated an "accelerated aging phenomenon" for adults aging with CP, with inflammation and alterations in several vital signs posing as shared risk factors for mild cognitive impairment (MCI) and serving as plausible physiological determinants of this phenomenon (2).…”