Can Women with Mild Cognitive Impairment Revert Back to Normal Cognition?

BACKGROUND AND PURPOSE:

  • Reversion to normal cognition (NC) from mild cognitive impairment (MCI) is possible, although most individuals with MCI do progress to dementia
  • Iraniparast et al. (Neurology, 2022) estimated transition rates from mild cognitive impairment (MCI) to normal cognition (NC) and dementia as well as associated impact of risk factors

METHODS:

  • Secondary analysis of longitudinal data
    • Nun Study
    • Cognitive ability of cohort of religious sisters assessed at baseline and yearly until death or study end (12 annual assessments)
    • ≥75 years
  • Population
    • Women from the Nun Study Cohort
  • Exposures
    • Age
    • APOE
      • e4 allele of the APOE gene increases risk for late-onset Alzheimer disease
    • Cognitive reserve indicators
      • Education
      • Academic performance: High school grades
      • Written language skills: Idea density | Grammatical complexity
  • Study design
    • Modelling was used to estimate transition between cognitive states
    • Transitions were considered
      • Reversible between NC and MCI
      • Nonreversible from dementia and MCI
  • Primary outcome
    • Instantaneous transition rates between NC, MCI and dementia
    • Rate of reversion to NC vs progression to dementia

RESULTS:

  • 619 participants
    • MCI during study period: 472
  • MCI patient outcomes during study period
    • ≥1 reverse transition to NC: 30.3%
    • Never developed dementia: 83.9%
      • Mean follow-up: 8.6 years
  • In models that adjusted for age group and APOE
    • Higher level of education significantly increased the relative rate ratio (RR) of reversion vs. progression
      • Bachelor’s degree: aRR ratio 2.60 (95% CI, 1.05 to 6.45)
      • Master’s degree or higher: aRR ratio 2.94 (95% CI, 1.27 to 7.22)
  • Cognitive reserve indicators were significantly associated with a higher adjusted RRs of reversion vs. progression
    • Higher vs. lower levels for English grades
      • RR ratio: 1.83 (95% CI, 1.07 to 3.14)
    • Idea density
      • RR ratio: 3.93 (95% CI, 1.30 to 11.92)
    • Grammatical complexity
      • RR ratio: 5.78 (95% CI, 1.56 to 21.42)

CONCLUSION:

  • Many participants with MCI did not progress to dementia, and in ~30% of cases actually experienced reversion to normal cognition
  • Indicators of cognitive reserve, such as education level and written language skills, were associated with higher rates of reversion vs progression
  • Limitations of the study include: The Nun Study cohort may not be generalizable | Transitions may reflect cognitive reserve but may also reflect normal variation over time
  • The authors state

Knowledge of predictors of reversion from MCI to NC is important to inform the design and interpretation of clinical trials, given that a substantial proportion of participants may experience improvement from MCI to NC even without intervention

Evidence of predictors of these reverse transitions may also inform population-level intervention strategies targeting these characteristics to prevent or postpone MCI and dementia

Learn More – Primary Sources:

Cognitive Reserve and Mild Cognitive Impairment: Predictors and Rates of Reversion to Intact Cognition vs Progression to Dementia

Does Maternal COVID-19 Vaccination Protect Against Infant Hospitalization Due to COVID?

BACKGROUND AND PURPOSE:

  • Halasa et al. (CDC MMWR, 2022) assessed the effectiveness of maternal completion of a 2-dose mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization in infants

METHODS:

  • Test-negative, case-control study
    • Real-world evaluation at 20 US pediatric hospitals during a period of Delta and Omicron variant circulation
  • Participants
    • Infants aged <6 months admitted outside of their birth hospitalization to a pediatric hospital during July, 2021 to January, 2022
      • Case infants had a positive COVID-19 test
      • Control infants had a negative COVID-19 test
  • Exposure
    • Maternal vaccination ≥14 days before delivery
      • Defined as completion of a 2-dose series of either Pfizer-BioNTech or Moderna mRNA COVID-19 vaccine
  • Study design
    • Control-infants were matched to case-infants by site and were hospitalized within 3 to 4 weeks of a case-infant’s admission date
    • In a secondary analysis, effectiveness of maternal receipt of the second dose of COVID-19 vaccination early in pregnancy (within the first 20 weeks) and late in pregnancy (21 weeks through 14 days before delivery) was assessed
  • Primary outcome
    • Vaccine effectiveness (VE) of maternal vaccination against infant COVID-19 hospitalization

RESULTS:

  • Case infants: 176 | Control infants: 203
    • Median age 2 months
    • Had at least one underlying medical condition: 21%
    • Born premature (<37 weeks): 22%
  • Effectiveness of maternal vaccination during pregnancy against COVID-19 hospitalization in infants aged <6 months
    • VE: 61% (95% CI, 31 to 78%)
  • Effectiveness of a completed 2-dose COVID-19 vaccination series early in pregnancy (first 20 weeks)
    • VE: 32% (95% CI, –43% to 68%)
  • Effectiveness of vaccine completion late in pregnancy (21 weeks through 14 days before delivery)
    • VE: 80% (95% CI, 55 to 91%)

CONCLUSION:

  • Maternal COVID-19 immunization appears to provide protection to infants through passive transplacental antibody transfer
  • Maternal vaccination had a VE of 61% for preventing COVID-19 hospitalization in infants
  • The authors state

Overall, these findings indicate that maternal vaccination during pregnancy might help protect against COVID-19 hospitalization among infants aged <6 months

Learn More – Primary Sources:

Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19–Associated Hospitalization in Infants Aged <6 Months — 17 States, July 2021–January 2022

Does Epidural Use During Vaginal Delivery Reduce the Risk of Severe Maternal Morbidity?

BACKGROUND AND PURPOSE:

  • Guglielminotti et al. (JAMA Network Open, 2022) assessed the association between the use of labor neuraxial analgesia for vaginal delivery and Severe Maternal Morbidity (SMM)

METHODS:

  • Population-based cross-sectional study
    • Data derived from hospital discharge records from New York between January 2010 and December 2017
  • Population
    • 5 to 49 years
    • Undergoing first vaginal delivery
  • Exposures
    • Neuraxial analgesia: Epidural or combined spinal-epidural
    • No neuraxial analgesia
  • Study design
    • Odds ratios (OR) of SMM associated with neuraxial analgesia were estimated using inverse propensity score–weighting and stratified according to
      • Race and ethnicity (non-Hispanic White vs racial and ethnic minority women, including non-Hispanic Asian or Pacific Islander, non-Hispanic Black, Hispanic, and other race and ethnicity)
      • The comorbidity index for obstetric patients (low-risk vs high-risk women)
  • Primary outcome
    • Severe maternal morbidity (SMM)
  • Secondary outcome
    • Postpartum hemorrhage (PPH)

RESULTS:

  • 575,524 included women
    • Mean age: 26 (SD, 6) years
    • Race/ethnicity
      • Non-Hispanic Asian or Pacific Islander: 8.0%
      • Non-Hispanic Black: 15.4%
      • Hispanic: 18.2%
      • Non-Hispanic White: 44.9%
      • Other race and ethnicity: 13.0%
    • Comorbidity index
      • Low-risk: 69.6%
      • High-risk: 30.4%
    • Received neuraxial analgesia: 47.4%
  • Incidence of SMM and PPH
    • SMM: 1.3%
      • Of these, PPH: 35.6%
  • Incidence of SMM by neuraxial analgesia exposure, before weighting
    • With neuraxial analgesia: 1.3%
    • No neuraxial analgesia: 1.4%
  • There was a decreased risk of SMM associated with neuraxial analgesia
    • Risk difference for SMM: −0.21% (95% CI, −0.30 to −0.12)
    • Adjusted OR 0.86 (95% CI, 0.82 to 0.90)
  • This association was similar between
    • Non-Hispanic White women and racial and ethnic minority women
    • Low-risk and high-risk women
  • More than one-fifth of the observed association of neuraxial analgesia with the risk of SMM was mediated through the decreased risk of PPH
    • 21% (95% CI, 14 to 28%)

CONCLUSION:

  • Neuraxial analgesia exposure during vaginal delivery is associated with a 14% decreased risk of severe maternal morbidity
    • This associated risk reduction was similar across race, ethnicity, and comorbidity index
    • More than 20% of the observed SMM risk reduction was due to a decreased risk of PPH
  • Limitations of the study include
    • Oservational design which demonstrates association but not causation | Only intrapartum SMM documented, not the 15% of severe adverse outcomes that occur following discharge
  • The authors suggest the following reasons why neuraxial analgesia may reduce PPH and SMM
    • Earlier evaluation and management of early PPH due to enhanced maternal monitoring and early detection of blood loss following delivery
    • Good IV access
    • Continuous anesthesia availability and oversight

Learn More – Primary Sources:

Use of Labor Neuraxial Analgesia for Vaginal Delivery and Severe Maternal Morbidity

How Effective are IUDs Compared to Tubal Ligation?

BACKGROUND AND PURPOSE: 

  • Schwarz et al. (Journal of General Internal Medicine, 2022) compare the effectiveness and safety of IUDs to laparoscopic tubal ligation for Medicaid clients

METHODS: 

  • Retrospective cohort study
    • California database
    • Medicaid claims data
  • Population
    • IUD placed or laparoscopic tubal ligation
    • Procedure performed between 2008 and 2014
  • Exposures
    • IUD placement
    • Tubal ligation
  • Study design
    • Study included stakeholder advisory board including patients and clinicians
    • Linear regression models used to test associations between contraceptive procedure and outcomes
    • Adjustments for sociodemographic variables and pre-procedure health status
  • Primary outcome
    • Contraceptive failure
    • Complications
    • Pain in first year post-procedure

RESULTS: 

  • Levonorgestrel IUD: 35,705 patients | Copper IUD: 23,628 patients | Tubal ligation: 23,965 patients
  • In unadjusted analyses, rates of pregnancy within 1 year were similar among the groups
    • Levonorgestrel IUD: 2.40%
    • Copper IUD: 2.99%
    • Tubal ligation: 2.64%
  • In adjusted analyses, compared to tubal ligation, pregnancy was less common following placement of
    • Levonorgestrel IUD
      • Adjusted incident rate ratio (aIRR) 0.72 (95% CI, 0.64 to 0.82)
    • Copper IUD
      • aIRR 0.92 (95% CI, 0.82 to 1.05)
  • Procedural complications such as infection were significantly less common with IUD placement than tubal ligation
    • IUD placement: 0.35%
    • Tubal ligation: 2.91%
  • Claims for pelvic and abdominal pain decreased in frequency over time regardless of contraceptive approach
  • At 6 to 12 months post-procedure, pelvic pain claims were less common after
    • Levonorgestrel IUD placement
      • aIRR 0.69 (95% CI, 0.65 to 0.73)
    • Copper IUD placement
      • aIRR 0.70 (95% CI, 0.66 to 0.75)
  • Results unchanged even after excluding patients at highest risk for post-procedure complications

CONCLUSION: 

  • Among patients with medicaid insurance, placement of a levonorgestrel or copper IUD is at least as effective at preventing pregnancy as tubal ligation 1-year post-procedure
  • Compared to tubal ligation, pregnancy within 1 year was
    • Lower than laparoscopic tubal ligation
    • Similar for copper IUD
  • Pain and infection were less common in patients who received an IUD vs tubal ligation
  • The authors state

As desire for reversal of tubal ligation is known to occur, it is important that all patients considering tubal ligation receive thorough counseling regarding the comparative safety and effectiveness of IUC prior to undergoing tubal ligation


Learn More – Primary Sources: 

Comparative Effectiveness and Safety of Intrauterine Contraception and Tubal Ligation

Can Vaccination Lead to Improved Long-COVID Symptoms?

BACKGROUND AND PURPOSE: 

  • Risk factors and disease progression of Long-COVID or post-acute sequelae of SARS-CoV-2 infection are not well understood 
    • It isn’t clear whether vaccination can help prevent or improve symptoms of long-COVID 
  • Nehme et al. (Journal of General Internal Medicine, 2022) described the association of vaccination and the evolution of six cardinal symptoms embodying post-acute sequelae of SARS-CoV-2  

METHODS: 

  • Survey based study 
  • Participants 
    • Individuals who previously tested positive for SARS-CoV-2 infection (RT-PCR test) at a testing center in Switzerland  
    • Survey was sent between April 23 to July 27, 2021 
  • Exposures 
    • Post-acute sequelae of SARS-CoV-2 
    • Vaccination status 
  • Study design 
    • At the time of the study, the public health recommendations in Switzerland were for previously infected individuals to preferably receive one dose of vaccination only 
  • Primary outcome 
    • Persistence of symptoms  
      • Fatigue | Difficulty concentrating or memory loss | Loss of or change in smell | Loss of or change in taste | Shortness of breath | Headache 

RESULTS: 

  • 2094 participants 
    • Vaccinated, one dose: 26.6% 
    • Vaccinated, two doses: 20.5% 
  • Symptom status following vaccination 
    • Symptoms disappeared: 30.8% 
    • Symptoms improved: 35.5% 
    • Symptoms remained stable: 28.7% 
    • Symptoms worsened: 3.3% 
  • Vaccination (one or two doses) was associated with a decreased prevalence of the six cardinal post-SARS-CoV-2 symptoms 
    • Adjusted odds ratio (aOR) 0.72 (95% CI, 0.56 to 0.92) 
  • Vaccination with 2 doses was associated with a decreased prevalence of 
    • Dyspnea: aOR 0.34 (95% CI, 0.14 to 0.82) 
    • Change in taste: aOR 0.38 (95% CI, 0.18 to 0.83) 
    • Any one symptom: aOR 0.60 (95% CI, 0.43 to 0.83) 

CONCLUSION: 

  • Compared to no vaccination, participants who were vaccinated reported improvement in post-acute SARS-CoV-2 sequelae 
  • The authors state 

If confirmed, this would mean that vaccination not only prevents infection but also can potentially improve post-acute sequelae of SARS-CoV-2 

Learn More – Primary Sources: 

Symptoms After COVID-19 Vaccination in Patients with Post-Acute Sequelae of SARS-CoV-2 

RCT Results: Paxlovid and Risk Reduction for Severe Progression of COVID-19  

BACKGROUND AND PURPOSE: 

  • Hammond et al. (NEJM, 2022) evaluated the safety and efficacy of nirmatrelvir plus ritonavir (Paxlovid) in nonhospitalized adults with mild-to-moderate COVID-19 at high risk for progression to severe disease 

METHODS: 

  • Phase 2-3 double-blind, randomized, controlled trial 
  • Participants 
    • Symptomatic 
    • Unvaccinated 
    • Nonhospitalized  
    • At high risk for progression to severe COVID-19 
  • Interventions 
    • Nirmatrelvir group: 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) every 12 hours for 5 days 
    • Control group: placebo  
  • Study design 
    • Planned interim analysis was conducted on patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population) 
  • Primary outcome 
    • COVID-19-related hospitalization or death from any cause through day 28 
    • Viral load 
    • Safety  

RESULTS: 

  • Nirmatrelvir: 1120 participants | Control: 1126 participants 
  • In the planned interim analysis (774 patients) fewer patients in the treatment group were hospitalized or died by day 28 
    • Incidence of hospitalization or deaths  
      • Nirmatrelvir group: 0.77% (0 deaths)  
      • Control: 7.01% (7 deaths)  
    • Difference of −6.32 percentage points (95% CI, –9.04 to –3.59; P<0.001) 
    • Relative risk (RR) reduction: 89.1% 
  • Efficacy was maintained in the final analysis 
    • Difference between groups: −5.81 percentage points (95% CI, −7.78 to −3.84); P<0.001 
    • RR reduction: 88.9% 
  • All 13 deaths occurred in the control group 
  • When treatment was initiated within 3 days of treatment, viral load was lower in the nirmaltrelvir group at day 5 of treatment 
    • Adjusted mean difference: −0.868 log10 copies per mL 
  • The incidence of adverse events that emerged during the treatment period was similar in the two groups 
    • Any adverse event 
      • Nirmatrelvir: 22.6%  
      • Control: 23.9% 
    • Serious adverse events 
      • Nirmaltrelvir: 1.6% 
      • Control: 6.6% 
    • Adverse events leading to discontinuation of the drugs or placebo 
      • Nirmaltrelvir: 2.1%  
      • Control 4.2% 
  • The following occurred more frequently in the nirmaltrelvir group 
    • Dysgeusia  
      • Nirmaltrelvir: 5.6% 
      • Control: 0.3% 
    • Diarrhea  
      • Nirmaltrelvir: 3.1% 
      • Control: 1.6% 

CONCLUSION: 

  • Risk of progression to severe COVID-19 was reduced by ~89% for symptomatic COVID-19 patients who began a 5 day course of nirmatrelvir plus ritonavir 
  • Unlike monoclonal antibodies, this treatment can be taken orally and targets an enzyme necessary for general viral replication, making it less susceptible to different SARS-CoV-2 variants   

Learn More – Primary Sources: 

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19 

Meta-Analysis: Which Interventions are Best for Preventing Spontaneous Preterm Birth?  

BACKGROUND AND PURPOSE: 

  • Care et al. (BMJ, 2022) performed a network meta-analysis of various treatment options for the prevention of spontaneous preterm birth in at-risk women  

METHODS: 

  • Systematic review with Bayesian network meta-analysis
  • Study inclusion criteria
    • RCTs
    • Study participants who are at high risk of spontaneous preterm birth due to history of spontaneous preterm birth or short cervical length
    • Data included assessment of treatment options
  • Study design
    • Treatments: Bed rest | Cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage) | Cervical pessary | Fish oils or omega fatty acids | Nutritional supplements (zinc) | Progesterone (intramuscular, oral, or vaginal) | Prophylactic antibiotics | Prophylactic tocolytics | Combinations of interventions
    • Controls: Placebo or no treatment
    • Relative treatment effects (odds ratios and 95% credible intervals) and certainty of evidence were calculated for outcomes of preterm birth <34 weeks and perinatal death
  • Primary outcome
    • Preterm birth <34 weeks
    • Perinatal death
    • Other maternal and fetal outcomes

RESULTS: 

  • 61 studies | 17,273 pregnant women

Preterm Birth <34 weeks

  • Compared to placebo or no treatment, vaginal progesterone was associated with fewer women with preterm birth <34 weeks
    • Odds ratio (OR) 0.50 (95% CrI, 0.34 to 0.70); high certainty of evidence
  • Effect size of treatment was highest for Shirodkar cerclage, but certainty was low
    • OR 0.06 (95% CrI, 0.00 to 0.84); low certainty of evidence
  • The following treatments may also reduce preterm birth <34 weeks
    • 17OHPC (17α-hydroxyprogesterone caproate)
      • OR 0.68 (95% CrI, 0.43 to 1.02); moderate certainty
    • Vaginal pessary
      • OR 0.65 (95% CrI, 0.39 to 1.08); moderate certainty
    • Fish oil or omega 3
      • OR 0.30 (95% CrI, 0.06 to 1.23); moderate certainty

Perinatal death

  • Compared to placebo or no treatment, vaginal progesterone was the only treatment that showed clear evidence of benefit for reducing perinatal death
    • OR 0.66 (95% CrI, 0.44 to 0.97); moderate certainty
  • The following treatments might reduce perinatal death rates, but credible intervals could not exclude the possibility of harm
    • 17OHPC
      • OR 0.78 (95% CrI, 0.50 to 1.21); moderate certainty
    • McDonald cerclage
      • OR 0.59 (95% CrI, 0.33 to 1.03); moderate certainty
    • Unspecified cerclage
      • OR 0.77 (95% CrI, 0.53 to 1.11); moderate certainty
  • Only progesterone treatments are associated with reduction the following neonatal outcomes
    • Neonatal respiratory distress syndrome
    • Neonatal sepsis
    • Necrotizing enterocolitis
    • Admission to neonatal intensive care unit

CONCLUSION: 

  • Vaginal progesterone is the best preventative treatment option for asymptomatic women at risk of preterm birth due to short cervix and history of preterm birth 
  • The authors suggest that future trials use vaginal progesterone as the ‘gold standard’ comparator group when assessing other treatment options 
    • Administering placebo or no treatment will be difficult to offer 
  • The authors state 

Vaginal progesterone is currently the best preterm birth prevention treatment for women with a singleton pregnancy who are asymptomatic but at high risk of preterm birth 

No other treatment can be regarded as superior, but promising results have been observed for alternative routes of administration (oral, intramuscular), and treatments such as cerclage and pessary 

Learn More – Primary Sources: 

Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis 

Is there a Causal Link Between Obesity and Female Reproductive Disorders? 

BACKGROUND AND PURPOSE: 

  • Observational studies have found an association between obesity and adverse reproductive outcomes 
  • Venkatesh et al. (PloS Medicine, 2022) estimated observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive disorders 

METHODS: 

  • Mendelian randomization study on prospective cohort data 
    • Data derived from the UK Biobank 
  • Population 
    • Individuals self-identifying as females of white ancestry 
  • Exposures 
    • BMI  
    • Waist-to-hip ratio (WHR): Waist/hip circumference 
    • WHR adjusted for BMI (WHRadjBMI) 
  • Study design 
    • Systematic genetics-based causal investigation 
    • Logistic regression models were used to estimate the associations of BMI, WHR, and WHRadjBMI with prevalence of primary outcomes 
  • Primary outcomes 
    • Endometriosis  
    • Heavy menstrual bleeding (HMB) 
    • Infertility 
    • Self-reported stillbirth 
    • Spontaneous miscarriage or termination 
    • PCOS  
    • Pre-eclampsia 
    • Uterine fibroids (UF) 

RESULTS: 

  • BMI, WHR, and WHRadjBMI were all associated with uterine fibroids, PCOS, heavy menstrual bleeding and preeclampsia, both 
    • Observationally: Odds ratios (ORs) 1.02 to 1.87 per 1-SD increase in obesity trait 
    • Genetically: ORs 1.06 to 2.09 
  • Genetically predicted visceral adipose tissue (VAT) mass was associated with 
    • Heavy menstrual bleeding (P=0.0130) 
      • OR per 1-kg increase in predicted VAT mass 1.32 (95% CI, 1.06 to 1.64) 
    • PCOS (P=0.0000324) 
      • OR 1.15 (95% CI, 1.08 to 1.23) 
    • Preeclampsia (P=0.000000665) 
      • OR 3.08 (95% CI, 1.98 to 4.79) 
  • Increased waist circumference posed a higher genetic risk for the development of these disorders and uterine fibroids vs increased hip circumference 
    • Waist circumference: ORs 1.16 to 1.93 
    • Hib circumference: ORs 1.06 to 1.10 
  • Between 20% and 50% of the total genetically predicted association between obesity and preeclampsia was mediated by  
    • Leptin 
    • Fasting insulin 
    • Insulin resistance 
  • Reproductive conditions clustered based on shared genetic components of their etiological relationships with obesity 

CONCLUSION: 

  • Indices of obesity were associated with increased risk of female reproductive disorders, particularly uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and preeclampsia 
  • Limitations to this study include the low prevalence of female reproductive conditions among women in the UK Biobank 
  • Endocrine factors, such as leptin and insulin resistance, may be drivers of the underlying causative mechanism that results in adverse reproductive outcomes in women with obesity 
  • The authors state 

The strongest association of generalized obesity was found with pre-eclampsia, while more modest associations were observed for nearly all other studied conditions 

Learn More – Primary Sources: 

Obesity and risk of female reproductive conditions: A Mendelian randomisation study 

Is Preterm Birth More Common in Women with Endometriosis? 

BACKGROUND AND PURPOSE: 

  • Whether endometriosis is associated with worse pregnancy outcomes is still unclear 
  • Marcellin et al. (JAMA Network Open, 2022) evaluated the association between the presence of endometriosis and preterm birth

METHODS: 

  • Multicenter, prospective cohort study 
    • 7 academic units in France  
  • Participants 
    • Singleton pregnancies  
    • Follow-up <22 weeks’ gestation  
    • Neonates delivered ≥22 weeks’ 
  • Exposures 
    • Endometriosis: Documented history with 3 possible phenotypes 
      • Isolated superficial peritoneal endometriosis (SUP) 
      • Ovarian endometrioma (OMA; potentially associated with SUP) 
      • Deep endometriosis (DE; potentially associated with SUP and OMA) 
    • Control: No clinical endometriosis symptoms  
  • Study design 
    • Association between endometriosis and the primary outcome was assessed through univariate and multivariate logistic regression analyses 
    • Adjusted for preterm risk factors 
      • Maternal age | BMI before pregnancy | Country of birth | Parity | Previous cesarean delivery | History of myomectomy and hysteroscopy, and preterm birth 
    • The same analysis was performed according to the 3 endometriosis phenotypes  
  • Primary outcome 
    • Preterm birth between 22w0d and 36w6d 

RESULTS: 

  • 1351 study participants 
    • Mean (SD) age 32.9 (5.0) years 
    • Endometriosis diagnosis: 470 participants 
      • SUP: 10.2% 
      • OMA: 17.7% 
      • DE: 72.1% 
  • There was no difference in the rate of preterm birth between groups 
    • Endometriosis: 7.2% 
    • Control: 6.0% 
    • P=0.38 
  • After adjustment, endometriosis was still not associated with preterm birth 
    • aOR 1.07 (95% CI, 0.64 to 1.77) 
  • Results were comparable across different disease phenotypes (P=0.84) 
    • SUP: 6.2% preterm birth  
    • OMA: 7.2% preterm birth 
    • DE: 7.4% preterm birth 

CONCLUSION: 

  • In this cohort, there was no association between endometriosis and incidence of preterm birth 
  • Endometriosis phenotype did not modify this finding 
  • The authors state 

Pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth; thus, monitoring their pregnancy beyond the normal protocols or changing management strategies may not be warranted 

Learn More – Primary Sources: 

Association Between Endometriosis Phenotype and Preterm Birth in France 

Is there an Association between Multiple Morbidities and Subsequent Dementia?  

BACKGROUND AND PURPOSE: 

  • Ben Hassen et al. (BMJ, 2021) examined the association of midlife and late life multimorbidity with incident dementia 

METHODS: 

  • Prospective cohort study 
    • Data derived from the Whitehall II study (started in 1985 to 1988) 
  • Participants 
    • British adults  
    • 35 to 55 years at baseline 
  • Exposures 
    • Multimorbidity 
  • Study design 
    • Multimorbidity: ≥2 chronic diseases 
    • Follow-up for primary outcome took place from 1985 through 2019 
    • Cause specific Cox proportional hazards regression used to examine the association of multimorbidity and dementia 
      • Overall 
      • At age 55, 60, 65, and 70  
    • Adjustment for  
      • Sociodemographic factors | Health behaviors | Competing risk of death 
  • Primary outcome 
    • Incident dementia  

RESULTS: 

  • 10,095 adults 
    • Prevalence of multimorbidity 
      • At age 55: 6.6% 
      • At age 70: 31.7% 
    • Incident dementia cases: 639 
      • Median follow-up 31.7 years 
  • Multimorbidity at age 55 was associated with subsequent risk of dementia 
    • Difference in incidence rate per 1000 person years: 1.56 (95% CI, 0.62 to 2.77) 
    • Hazard ratio: 2.44 (95% CI, 1.82 to 3.26) 
  • This association got progressively weaker as onset of multimorbidity occurred at older age, e.g., at age 65 
    • Onset of multimorbidity <55 years 
      • 3.86 per 1000 person years higher incidence of dementia (95% CI, 1.80 to 6.52) 
      • HR 2.46 (95% CI, 1.80 to 2.26) 
    • Onset of multimorbidity between 60 and 65 years 
      • 1.85 per 1000 person years higher incidence (95% CI, 0.64 to 3.39) 
      • HR 1.51 (95% Ci, 1.16 to 1.97) 
  • Severe multimorbidity (≥3 chronic diseases) at age 55 was associated with a higher incidence of dementia 
    • 5.22 per 1000 person years higher incidence of dementia (95% CI, 1.14 to 11.95) 
    • HR 4.96 (95% CI, 2.54 to 9.67) 
  • Severe multimorbidity onset by age 70 was associated with a weaker incident dementia  
    • 4.49 per 1000 person years higher incidence (95% CI, 2.33 to 7.19) 
    • HR 1.65 (95% CI, 1.25 to 2.18) 

CONCLUSION: 

  • Multimorbidity is associated with incident dementia, and this association is stronger when multiple chronic conditions manifest earlier in life 
  • The authors state 

These findings highlight the role of prevention and management of chronic diseases over the course of adulthood to mitigate adverse outcomes in old age 

Multimorbidity is already known to affect use of healthcare services, quality of life, and risk of mortality; our study adds dementia to that list 

Learn More – Primary Sources: 

Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study 

Does Coffee Consumption Reduce Dementia Risk? 

BACKGROUND AND PURPOSE: 

  • Consumption of coffee or caffeine may help prevent dementia, possibly by reducing amyloid-β (Aβ) in the brain 
    • Data is currently limited  
  • Matsushita et al. (Journal of the American Geriatrics Society, 2021) examined association between caffeine consumption and dementia risk  

METHODS: 

  • Cohort study 
    • Murakami cohort study targeted all residents between 40 and 74 years, living in Murakami city, Sekikawa village, and Awashimaura village of Niigata Prefecture in Japan 
  • Participants 
    • Adults aged 40 to 74 years  
    • Japanese Cohort   
  • Exposures 
    • Consumption levels of coffee or green tea 
  • Study design 
    • Caffeine consumption was estimated from self-reported amount of coffee or green tea consumption  
    • Incidence of primary outcome was determined from a long-term care insurance database 
    • Covariate Analyses: Demographic factors | BMI | Physical activity | Energy | Smoking | Drinking | Disease history 
    • Adjusted hazard ratio (HR) calculated using Cox proportional hazards models 
  • Primary outcome 
    • Incident dementia 

RESULTS: 

  • 13,757 participants 
    • Follow-up: 8.0 years 
    • Dementia cases during the study period: 309 
  • Compared to participants who consumed <26 ml (0.9 oz) of coffee per day (1st quintile), those that consumed ≥326 ml (11 oz) per day (5th quintile) had reduced dementia risk  
    • HR 0.49 (95% CI, 0.30 to 0.79) 
    • Adjusted p for trend=0.0014 
    • In subgroup analysis 
      • Overall significant among men, not women  
      • Among ≥60 years, 5th quintile had lower HR (0.5; 95% CI, 0.29 to 0.85) for both men and women  
  • Compared to those who did not consume coffee, higher cups per day was associated with reduced dementia risk in men and women combined    
    • 2 to 2.9 cups/day: HR 0.69 (95% CI, 0.48 to 0.98) 
    • ≥3 cups/day: HR 0.53 (95% CI, 0.31 to 0.89, respectively 
  • Participants with higher caffeine consumption had a significantly lower HR than those who consumed <92 mg per day 
    • adjusted p for trend=0.0004 
  • There was no association between green tea consumption and reduced dementia risk overall but marginal significance seen in the 60 to 69 years age subgroup 

CONCLUSION: 

  • Higher levels of daily coffee and caffeine intake were dose-dependently associated with reduced dementia risk, especially among men  
  • Authors suggest possible reasons for differences between men and women  
    • Men have a higher degree of oxidative stress and benefits of caffeine may include antioxidant effect  
    • Effects of caffeine on sex hormones may differ by sex  

Learn More – Primary Sources: 

Association of coffee, green tea, and caffeine with the risk of dementia in older Japanese people