Tag Archives: cognitive impairment

Study: PPIs Did Not Cause Dementia in Older Adults

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Thanks to Ben Gold for encouraging me to review this article:

RS Mehta et al. Gastroenterol 2023; ; 165: 564-572. Open Access! Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study

The authors used data from ASPirin in Reducing Events in the Elderly (ASPREE), a randomized prospective trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities (enrollment 2010-2014). Final cognitive testing was done in 2017. Key Findings:

  • Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88, cognitive impairment without dementia (multivariable hazard ratio, 1.00), or with changes in overall cognitive test scores over time.
  • Also, no associations were observed between H2RA use and all cognitive endpoints.

My take: ” These data provide reassurance about the safety of long-term use of PPIs among older adults.” PPIs are unlikely to have negative effects on cognition.

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More is Not Better: Protein for Preterm Infants

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FH Bloomfield et al. NEJM 2022; 387: 1661-1672. Early Amino Acids in Extremely Preterm Babies

My take: For preterm infants <1000 gram, this study showed that the usual dosing of amino acids 2.5 gram to 3.5 gram per day (the placebo group) appeared to have better secondary outcomes (though within confidence intervals) than those who received an additional 1 gram per day.

Slides from video summary:

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Docosahexaenoic Acid (DHA) for Preterm Infants and Intelligence

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JF Gould et al. NEJM 2022; 387: 1579-1588. Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years

Background: “Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks’ gestation do not receive the normal supply of DHA.”

In this randomized placebo-controlled study of infants born prior to 29 weeks gestation, DHA supplementation 60 mg/kg/day was given to the study group and cognitive outcomes were measured at 5 yrs. 480 (73%) had an full-scale intelligence quotient (FSIQ) score available — 241 in the DHA group and 239 in the control group.

Key findings:  FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group. Adverse events were similar in the two groups.

Short take video: DHA in Premature Infants

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The Elephant in the Transplant Room: Personhood

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A recent study and related editorial discuss the ethics and utilization of transplantation for children with intellectual disability.

In the study by Wightman et al, the researchers performed a retrospective cohort analysis of children receiving a first kidney, liver, or heart-alone transplant in the United Network for Organ Sharing dataset from 2008 to 2017. Key findings:

  • Definite intellectual disability accounted for 594 of 6747 (9%) first pediatric kidney-alone, 318 of 4566 (7%) first pediatric liver-alone, and 324 of 3722 (9%) first pediatric heart-alone transplant recipients. 
  • Children with intellectual disability account for 7%-9% of pediatric transplant recipients with comparable long-term outcomes to other pediatric recipients.
  • The article had a number of limitations including a lack of a standardized assessment of cognitive development.

In the editorial, the author “opposes the absolute exclusion of patients with intellectual disability and end-stage organ disease from transplantation waitlists provided that the candidates are expected to gain a predefined minimum benefit threshold of life-years and quality-adjusted-life years. Intellectual disability is one of many factors that should be considered in determining transplant eligibility and each candidate should have an individualized interdisciplinary assessment.”

In this commentary, it is noted that “the vast majority (85%) of individuals classified as having intellectual disability are able to live independently with minimum levels of support.” While the author would exclude those in a persistent vegetative state and those who were minimally conscious, otherwise he advocates “the candidate with intellectual disability should be given equal priority for organ transplantation.”

My view: The suitability for transplantation of individuals with intellectual disability centers on the issue of personhood; those who meet the threshold of personhood should be eligible to receive organ transplants without discrimination.  Wikipedia-Personhood: “Defining personhood is a controversial topic in philosophy and law and is closely tied with legal and political concepts of citizenship, equality, and liberty.”

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Does SMOFlipid Improve Neurocognitive Outcomes?

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M Thanhaeuser et al. J Pediatr 2020; 226: 142-148. A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis

This study evaluated neurodevelopmental outcomes using Bayley Scales. the authors provided a secondary outcome analysis of a double-blind randomized trial of 206 extremely low birth weight infants.  Participants received either SMOFlipid or soybean oil-based lipid. Lipids were dosed at </+ 3 g/kg/day.

Key findings:

  • Parenteral nutrition using a mixed lipid emulsion (SMOF) containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age
  • At 24 months of age, specifically, there was again no significant differences in any of the following areas (median values):
    • cognitive: SMOF: 95 & soybean oil: 95
    • language: SMOF: 89 & soybean oil 89
    • motor scores: SMO 94 & soybean oil: 94

Limitations: One of the reasons why this study did not find any difference is that it was not powered for assessment of neurodevelopmental outcomes. The authors provide other potential reasons:

  • DHA in SMOFlipid provided 43 mg/kg/d, while more than the soybean-lipid, is at the lower end of published fetal accretion rates (40-67 mg/kg/day)
  • DHA deficits may not have been pronounced enough in this study to see an effect of SMOFlipid on neurodevelopement
  • Full feeds were reached after 23 days (IQR, 17-37 days); thus, it is possible that infants with longer term dependency on parenteral nutrition would benefit more

My take: SMOFlipid has not been proven to have more favorable long-term neurocognitive effects than intralipid. However, for children with prolonged need for parenteral nutrition, SMOFlipid is more likely to allow full dosing which in itself may be an important contributor to better outcomes. That is, soybean-lipid emulsions are more likely to be reduced due to cholestasis and this could lead to nutritional deprivation.

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What to Expect After Pediatric Liver Transplantation: Cognitive Function and Quality of Life

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A recent study (D Ohnemus et al. Liver Transplantation 2020; 26: 45-56, editorial 9-11) examined health-related quality of life (HRQOL) and cognitive functioning approximately 15 years after liver transplantation (LT).

Study details:

Median age 16 years.  Original group was a SPLIT research cohort recruited from 20 centers and then tested at multiple time points; for this study, 8 sites of the original 20 were included.  It is noted that patients with serious neurologic injury were excluded. Among an initial group of 108, there were 79 available for potential enrollment.  In this group, 65 parent surveys were completed and 61 child surveys.

Key findings:

  • For cognitive and school functioning, 60% and 51% of parents reported “poor” functioning, respectively (>1 SD below the health mean).  41% of children rated their cognitive function as poor.
  • Adolescents’ self-reported overall HRQOL was similar to that of healthy children; in contrast, parents rated their teenage children as having significantly worse HRQOL than healthy children in all domains.
  • The cognitive score in the poor functioning group at the latest time point was lower than at first time point measurement (ages 5-6 years and at least 2 years after LT), “suggesting that difficulties intensified in adolescence for those who have problems in early childhood.”
  • Almost half had received special educational services.

The editorial notes that the PedsQL Cognitive Functioning Scale scores used by the investigators were considered subjective.  “The more objective PedsPCF scores fell within the normal range.”

My take: This report indicates that a majority of children are likely to have some cognitive deficits and many are likely to have reduced HRQOL following liver transplantation; in addition, if these problems are detected at a younger age, they are likely to persist.

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Briefly Noted: Ferritin Levels and Cognitive Outcomes

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PC Parkin et al. J Pediatr 2020; 217:189-91.

In this study, the authors conducted a secondary analysis of data from the Optimizing Early Child Development Study (Toronto) with 745 healthy children.  The authors note that the setting is from a high resource area with high maternal education.

Key finding:

  • In pediatric patients, 1-3 years, higher serum ferritin values were associated with higher cognitive function as measured by the Mullen Scales of Early Learning
  • Ferritin of 17 mcg/L or higher corresponded to maximum level of cognition

Based on this study, the authors recommend obtaining a ferritin level at 12 months of age at same time when a hemoglobin is recommended.

My take: The implication of this study is that iron deficiency, even in the absence of socioeconomic status, can have a detrimental effect on cognitive outcomes.

Related blog post: Nutrition Week (Day 6) Iron Deficiency in Breastfed Infants

 

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Neurocognitive Function with Pediatric Intestinal Failure

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Lately, there have been a lot of articles on neurocognitive function.  The latest (A Gold et al. JPGN 2020; 70: 225-31) describes the myriad of problems facing children with intestinal failure (IF). The authors literally used 12 different measures of neurocognitive and academic measures –though not all 28 subjects had each of these measures (Table 2).

Caveats:

  • The authors specifically excluded 5 children with severe neurodevelopmental problems that precluded participation in standardized assessment and 10 children who were transplant recipients.
  • Also, when judging the results, it is important to keep in mind that their cohort had a good maternal education level; 68% were college graduates.

Key findings:

  • 13 of 28 (46%) received a diagnosis of cognitive/learning DSM diagnosis
  • 29% met diagnostic criteria for a learning disability, 7% for ADHD, and 11% for intellectual disability; comparison Canadian prevalence rates are 4%, 5%, and 1% respectively
  • The number of first-year septic episodes was associated with poorer outcomes; ≥2 or more episodes increased the likelihood.
  • Sustained cholestasis was associated with poor outcomes
  • The average level of intellectual functioning in their sample of 28 children was within 1 standard deviation of the population mean

There are a lot of risk factors for neurodevelopment impairment in these children with IF: prematurity, nutritional status/specific nutrient deficiencies, cholestasis, need for anesthesia/surgeries

My take: More than half of children with IF had neurodevelopemental impairment.  In this cohort, recurrent sepsis in the first year of life and sustained cholestasis were associated risk factors.

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Sunrise in Sandy Springs

 

Feeling Guilty about Stopping Breastfeeding?

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From NY Times, Link: http://t.co/rBXCORx3mM

Excerpt:

Many women who are unable to breast-feed feel guilty about it and worry they may be depriving their children of a range of benefits. Groups like the American Academy of Pediatrics and the World Health Organization recommend six months of exclusive breast-feeding for all infants, citing studies that show breast milk is easily digestible and has nutrients that are superior to or absent from infant formulas, including immunological substances that reduce rates of infection and fatty acids important in brain development.

But now a new study suggests that many of the long-term benefits attributed to breast-feeding may be an effect not of breast-feeding or breast milk itself but of the general good health and prosperity of women who choose to breast-feed.

Researchers at Ohio State University compared 1,773 sibling pairs, one of whom had been breast-fed and one bottle-fed, on 11 measures of health and intellectual competency. The children ranged in age from 4 to 14 years.

The researchers recorded various health and behavioral outcomes in the sibling pairs, including body mass index, obesity, asthma, hyperactivity, reading comprehension, math ability and memory-based intelligence. The study, published online in Social Science & Medicine, found no statistically significant differences between the breast-fed and bottle-fed siblings on any of these measures.

By studying “discordant” siblings — one of whom had been breast-fed and the other not — the authors sought to minimize the possibility that racial, socioeconomic, educational or other differences between families could affect the results. Many earlier studies on breast-feeding failed to control for such factors, they say.

… researchers have consistently found large socioeconomic and racial disparities in breast-feeding rates. A C.D.C. survey in 2008 found that 75 percent of white infants and 59 percent of black infants were ever breast-fed, and in 2013, the agency reported that 47 percent of white babies but only 30 percent of black babies were still being breast-fed at 6 months. Compared with bottle-fed infants, breast-fed babies are more likely to be born into families with higher incomes, have parents with higher educational attainments, and live in safer neighborhoods with easier access to health care services.

Still, sibling studies such as this latest one do not solve all the problems of bias…

Geoff Der, a statistician at the University of Glasgow who has worked with the same data in previous studies, said that the findings in the present study were robust and the authors’ method for eliminating selection bias was powerful…“In a society with a clean water supply and modern formulas,” he said, “a woman who isn’t able to breast-feed shouldn’t be feeling guilty, and the likelihood that there’s any harm to the baby is pretty slim.”

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What is the long-term neurological outcome in Tyrosinemia Type 1?

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The answer to the blog post title: mild impaired cognitive function, according to a recent study (J Pediatr 2014; 164; 398-401).

Using a cross-sectional study, children (n=10) with tyrosinemia type 1 were compared with their unaffected siblings.  Intelligence was measured with Wechsler Scales. These children were treated with nitisinone (NTBC).  NTBC which was introduced in 1992 has markedly improved the survival of tyrosinemia by blocking the accumulation of toxic metabolites.  Liver dysfunction is controlled in >90% and the risk of liver cancer has been reduced as well.

Key results:

  • Average IQ score in tyrosinemia patients was lower than their siblings: 71 vs. 91 (P= .008).
  • In the five patients with repeated measurements, there was a gradual decline in IQ over time (240 months), from 96 to 69.

Why?

The authors do not know but speculate that cognitive impairment may have been overlooked previously due to the short life span of untreated patients.  While the lower IQ may be due to the treatment itself, “similarly low IQs in patients who stopped taking nitisone after undergoing liver transplantation argues against the acute toxicity of nitisinone.” Thus, elevated tyrosine/low phenylalanine levels, which occurs in patients on NTBC/restricted protein diet, may be related to cognitive impairment.