Potential Modifiable Risk Factors Research Articles

Modifiable Risk Factors for Alzheimer Disease and Related Dementias Among Adults Aged ≥45 Years - United States, 2019.

Alzheimer disease,* the most common cause of dementia, affects an estimated 6.5 million persons aged ≥65 years in the United States (1). A growing body of evidence has identified potential modifiable risk factors for Alzheimer disease and related dementias (ADRD) (1-3). In 2021, the National Plan to Address Alzheimer's Disease (National Plan) introduced a new goal to "accelerate action to promote healthy aging and reduce risk factors for Alzheimer's disease and related dementias" to help delay onset or slow the progression of ADRD (3). To assess the status of eight potential modifiable risk factors (i.e., high blood pressure, not meeting the aerobic physical activity guideline, obesity, diabetes, depression, current cigarette smoking, hearing loss, and binge drinking), investigators analyzed data from the cognitive decline module that was administered to adults aged ≥45 years in 31 states and the District of Columbia (DC)† in the 2019 Behavioral Risk Factor Surveillance System (BRFSS) survey. Among the risk factors, prevalence was highest for high blood pressure (49.9%) and lowest for binge drinking (10.3%) and varied by selected demographic characteristics. Adults with subjective cognitive decline (SCD),§ an early indicator of possible future ADRD (4), were more likely to report four or more risk factors than were those without SCD (34.3% versus 13.1%). Prevalence of SCD was 11.3% overall and increased from 3.9% among adults with no risk factors to 25.0% among those with four or more risk factors. Implementing evidence-based strategies to address modifiable risk factors can help achieve the National Plan's new goal to reduce risk for ADRD while promoting health aging.¶,*.

Explaining sex differences in risk of bloodstream infections using mediation analysis in the population-based HUNT study in Norway

Previous studies indicate sex differences in incidence and severity of bloodstream infections (BSI). We examined the effect of sex on risk of BSI, BSI mortality, and BSI caused by the most common infecting bacteria. Using causal mediation analyses, we assessed if this effect is mediated by health behaviours (smoking, alcohol consumption), education, cardiovascular risk factors (systolic blood pressure, non-HDL cholesterol, body mass index) and selected comorbidities. This prospective study included 64,040 participants (46.8% men) in the population-based HUNT2 Survey (1995–1997) linked with hospital records in incident BSI. During median follow-up of 15.2 years, 1840 (2.9%) participants (51.3% men) experienced a BSI and 396 (0.6%) died (56.6% men). Men had 41% higher risk of first-time BSI (95% confidence interval (CI), 28–54%) than women. Together, health behaviours, education, cardiovascular risk factors and comorbidities mediated 34% of the excess risk of BSI observed in men. The HR of BSI mortality was 1.87 (95% CI 1.53–2.28), for BSI due to S. aureus 2.09 (1.28–2.54), S. pneumoniae 1.36 (1.05–1.76), E. coli 0.97 (0.84–1.13) in men vs women. This study shows that men have higher risk of BSI and BSI mortality than women. One-third of this effect was mediated by potential modifiable risk factors for incident BSI.

Eveningness is associated with sedentary behavior and increased 10-year risk of cardiovascular disease: the SCAPIS pilot cohort

Chronotype reflects individual preferences for timing activities throughout the day, determined by the circadian system, environment and behavior. The relationship between chronotype, physical activity, and cardiovascular health has not been established. We studied the association between chronotype, physical activity patterns, and an estimated 10-year risk of first-onset cardiovascular disease (CVD) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. A cross-sectional analysis was performed in a middle-aged population (n = 812, 48% male). Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. Time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA) were derived from hip accelerometer. The newly introduced Systematic COronary Risk Evaluation 2 (SCORE2) model was used to estimate CVD risk based on gender, age, smoking status, systolic blood pressure, and non-HDL cholesterol. Extreme evening chronotypes exhibited the most sedentary lifestyle and least MVPA (55.3 ± 10.2 and 5.3 ± 2.9% of wear-time, respectively), with a dose-dependent relationship between chronotype and SED/MVPA (p < 0.001 and p = 0.001, respectively). In a multivariate generalized linear regression model, extreme evening chronotype was associated with increased SCORE2 risk compared to extreme morning type independent of confounders (β = 0.45, SE = 0.21, p = 0.031). Mediation analysis indicated SED was a significant mediator of the relationship between chronotype and SCORE2. Evening chronotype is associated with unhealthier physical activity patterns and poorer cardiovascular health compared to morning chronotype. Chronotype should be considered in lifestyle counseling and primary prevention programs as a potential modifiable risk factor.

Risk of Dementia After Hospitalization Due to Traumatic Brain Injury: A Longitudinal Population-Based Study.

Traumatic brain injury (TBI) is considered a potential modifiable dementia risk factor. We aimed to determine whether TBI actually increases the risk of dementia when adjusting for other relevant dementia risk factors. This was a national prospective longitudinal cohort study that included random and representative population samples from different parts of Finland of patients 25 through 64 years of age from 1992 to 2012. Major TBI was defined as a diagnosis of traumatic intracranial hemorrhage and hospital length of stay (LOS) ≥3 days and minor TBI was defined as a diagnosis of concussion and hospital LOS ≤1 day. Dementia was defined as any first hospital contact with a diagnosis of dementia, first use of an antidementia drug, or dementia as an underlying or contributing cause of death. Follow-up was until death or end of 2017. Of 31,909 participants, 288 were hospitalized due to a major TBI and 406 were hospitalized due to a minor TBI. There was a total of 976 incident dementia cases during a median follow-up of 15.8 years. After adjusting for age and sex, hospitalization due to major TBI (hazard ratio [HR] 1.51, 95% CI 1.03-2.22), but not minor TBI, increased the risk of dementia. After additional adjustment for educational status, smoking status, alcohol consumption, physical activity, and hypertension, the association between major TBI and dementia weakened (HR 1.30, 95% CI 0.86-1.97). The risk factors most strongly attenuating the association between major TBI and dementia were alcohol consumption and physical activity. There was an association between hospitalized major TBI and incident dementia. The association was diluted after adjusting for confounders, especially alcohol consumption and physical activity. Hospitalization due to minor TBI was not associated with an increased risk of dementia. This study provides Class I evidence that major TBI is associated with incident dementia.

Modifiable and non-modifiable risk factors for obstetric anal sphincter injury in a Norwegian Region: a case\u2013control study

BackgroundObstetric anal sphincter injury (OASI) is a common and severe complication of vaginal delivery and may have short- and long-term consequences, including anal incontinence, sexual dysfunction and reduced quality of life. The rate of OASI varies substantially between studies and national birth statistics, and a recent meta-analysis concluded that there is a need to identify unrecognized risk factors. Our aim was therefore to explore both potential modifiable and non-modifiable risk factors for OASI.MethodsWe performed a case–control study in a single center maternity clinic in South-Eastern Norway. Data were extracted retrospectively from an institutional birth registry. The main outcome measure was the occurrence of the woman’s first-time 3rd or 4th degree perineal lesion (OASI) following singleton vaginal birth after 30 weeks’ gestation. For each woman with OASI the first subsequent vaginal singleton delivery matched for parity was elected as control. The study population included 421 women with OASI and 421 matched controls who gave birth during 1990–2002. Potential risk factors for OASI were assessed by conditional logistic regression analyses.ResultsThe mean incidence of OASI was 3.4% of vaginal deliveries, but it increased from 1.9% to 5.8% during the study period. In the final multivariate regression model, higher maternal age and birthweight for primiparous women, and higher birthweight for the multiparous women, were the only non-modifiable variables associated with OASI. Amniotomy was the strongest modifiable risk factor for OASI in both primi- (odds ratio [OR] 4.84; 95% confidence interval [CI] 2.60–9.02) and multiparous (OR 3.76; 95% CI 1.45–9.76) women, followed by augmentation with oxytocin (primiparous: OR 1.63; 95% CI 1.08–2.46, multiparous: OR 3.70; 95% CI 1.79–7.67). Vacuum extraction and forceps delivery were only significant risk factors in primiparous women (vacuum: OR 1.91; 95% CI 1.03–3.57, forceps: OR 2.37; 95% CI 1.14–4.92), and episiotomy in multiparous women (OR 2.64; 95% CI 1.36–5.14).ConclusionsAmniotomy may be an unrecognized independent modifiable risk factor for OASI and should be further investigated for its potential role in preventive strategies.

Inhaled Corticosteroids, Vitamin K Antagonists and Amlodipine Were Associated with an Increased Risk of Acute Periprosthetic Joint Infection in Patients with Total Hip Arthroplasty: A Retrospective Case-Cohort Study.

The perioperative use of certain medication may influence the risk of developing a periprosthetic joint infection (PJI). Inhaled corticosteroids (ICSs) and cardiovascular drugs are widely used against pulmonary and cardiovascular diseases. While oral corticosteroids and anticoagulants have been shown to increase the risk of developing PJI, this is not clear for ICSs. In contrast, some cardiovascular drugs, such as amlodipine, nifedipine and statins, have been documented to show an antimicrobial effect, suggesting a synergistic effect with antibiotics in the treatment of (multi-resistant) microorganisms. We performed a case–cohort study to assess the association between the occurrence of PJI after THA and the use of inhaled corticosteroids, anticoagulants, or previously mentioned cardiovascular agents. In a cohort of 5512 primary THAs, we identified 75 patients with a PJI (1.4%), and randomly selected 302 controls. A weighted Cox proportional hazard regression model was used for the study design and to adjust for potential confounders (age, sex, smoking, and cardiovascular/pulmonary disease). We found ICS use (HR 2.6 [95% CI 1.1–5.9]), vitamin K antagonist use (HR 5.3 [95% CI 2.5–11]), and amlodipine use (HR 3.1 [95% CI 1.4–6.9]) to be associated with an increased risk of developing PJI after THA. The effect remained after correction for the mentioned possible confounders. The underlying diseases for which the medications are prescribed could also play a role in the mentioned association; we believe, however, that the usages of ICSs, vitamin K antagonists and amlodipine appear to be potential modifiable risk factors for PJI, and therefore have to be questioned during preoperative screening and consultation.

Daytime sleepiness and emotional and behavioral disturbances in Prader-Willi syndrome

Individuals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of individuals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for individuals with PWS (including 22 males) aged 4.4–24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28%; β = 0.028; p < 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29%; β = 0.023; p = 0.007). This relationship was not moderated by BMI Z-scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years.Conclusions: These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children.What is Known:• Individuals with Prader-Willi syndrome (PWS) commonly experience excessive daytime sleepiness and exhibit emotional/behavioral disturbances.• In the typically developing population, sleepiness is associated with emotional/behavioral disturbances, independently of sleep-disordered breathing..What is New:• This study found evidence for a direct link between daytime sleepiness and emotional/behavioral disturbances, independent of sleep-related breathing difficulties, sleep adequacy, and body mass index.• Excessive daytime sleepiness may be a modifiable risk factor for emotional/behavioral disturbances in PWS.

Physical Exercise, a Potential Non-Pharmacological Intervention for Attenuating Neuroinflammation and Cognitive Decline in Alzheimer's Disease Patients.

This narrative review summarises the evidence for considering physical exercise (PE) as a non-pharmacological intervention for delaying cognitive decline in patients with Alzheimer’s disease (AD) not only by improving cardiovascular fitness but also by attenuating neuroinflammation. Ageing is the most important risk factor for AD. A hallmark of the ageing process is a systemic low-grade chronic inflammation that also contributes to neuroinflammation. Neuroinflammation is associated with AD, Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders. Pharmacological treatment of AD is currently limited to mitigating the symptoms and attenuating progression of the disease. AD animal model studies and human studies on patients with a clinical diagnosis of different stages of AD have concluded that PE attenuates cognitive decline not only by improving cardiovascular fitness but possibly also by attenuating neuroinflammation. Therefore, low-grade chronic inflammation and neuroinflammation should be considered potential modifiable risk factors for AD that can be attenuated by PE. This opens the possibility for personalised attenuation of neuroinflammation that could also have important health benefits for patients with other inflammation associated brain disorders (i.e., Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders). In summary, life-long, regular, structured PE should be considered as a supplemental intervention for attenuating the progression of AD in human. Further studies in human are necessary to develop optimal, personalised protocols, adapted to the progression of AD and the individual’s mental and physical limitations, to take full advantage of the beneficial effects of PE that include improved cardiovascular fitness, attenuated systemic inflammation and neuroinflammation, stimulated brain Aβ peptides brain catabolism and brain clearance.

Recruitment & Retainment of Vascular Surgeons: Prophylactic Measures to Improve the Current Workforce Crisis

The vascular surgery workforce is in jeopardy with the current and increasing shortages. This study explores target populations for recruitment and aims to identify potential modifiable and nonmodifiable risk factors associated with reduced job satisfaction among practicing vascular surgeons to improve retention and prevent early retirement. A cross-sectional national survey of surgeons (n=1,043) was conducted from September 2016 to May 2017. Data included, demographic and occupational characteristics, as well as psychological, work-life balance, work-environment, and job-satisfaction variables. Surgeons were grouped into general surgery (n=507), obstetrics and gynecology (n=272), surgical subspecialties (n=212), and vascular surgery (n=52). Vascular surgeons were recategorized as more satisfied and less satisfied, and potential risk factors for job dissatisfaction were identified. As compared with general surgeons, obstetrics and gynecology, as well as other surgical subspecialties, vascular surgery tended to be male-dominated with higher rates of non-white, minority groups (P<0.05). Less vascular surgery respondents were found in the Midwest (P<0.001). Vascular surgeons worked more hours on average than other surgical fields and were less satisfied with work (P<0.05). Potential job dissatisfaction risk factors among vascular surgeons include: unhealthy work-life balance, poor camaraderie/coworker dissatisfaction, insufficient hospital support, hostile hospital culture, discontent with supervision, minimal patient diversity, dissatisfaction with work in general, and unhappiness with career choice (P<0.05). Recruiting new vascular surgery trainees while simultaneously preventing early retirement and attrition is critical to combatting the current workforce crisis. Potential interventions include (1) re-branding of the field with prioritization of work-life balance, (2) increasing hospital administration's support, (3) creating a collaborative work environment, and (4) facilitating personal accomplishment in work.

Associations between Alcohol Consumption Patterns and Risk of Multiple Myeloma: A Nationwide Cohort Study in South Korea.

Among the potential modifiable risk factors, the association between alcohol consumption and the risk of multiple myeloma remains controversial. We investigated the effects of weekly average alcohol consumption and drinking pattern on the risk of multiple myeloma using a nationwide representative database. We identified 11,737,467 subjects who participated in the Korean National Health Screening Program in 2009 and 2010. Cox regression analyses were performed to calculate the risk of multiple myeloma according to weekly alcohol consumption, drinking frequency, and amount per session. During a mean follow-up period of 6.8 years after a one-year time lag, 6,981 subjects (3,921 men and 3,060 women) were diagnosed with multiple myeloma. Compared with nondrinkers, all drinkers were at a significantly lower risk for multiple myeloma. The risk of multiple myeloma was reduced in a dose-dependent manner: mild drinkers [adjusted HR (aHR), 0.89; 95% confidence interval (CI), 0.84-0.95], moderate drinkers (aHR, 0.83; 95% CI, 0.76-0.91), and heavy drinkers (aHR, 0.76; 95% CI, 0.69-0.85). Furthermore, both drinking frequency and amount per drinking session showed inverse association with the risk of multiple myeloma. Our large population-based study suggested an inverse dose-dependent association between total average alcohol consumption and the risk of multiple myeloma, and drinking frequency and amount per drinking session seemed to not differ in their relative contribution to the risk of multiple myeloma. On the basis of the unprecedentedly large number of study population analyzed in this study, our study provides solid epidemiologic evidence of alcohol consumption on multiple myeloma risk.

Reliability of the Hip Extension Lower Exercise as a Measure of Eccentric Hamstring Strength

Hamstring strain injury (HSI) is a very common lower-body injury in field sports, and eccentric (ECC) hamstring strength is a potential modifiable risk factor, therefore having reliable eccentric hamstring strength assessments is critical. The aim of this study was to access test–retest reliability of the hip extension lower (HEL) exercise as a measure of ECC hamstring strength and inter-limb asymmetries. Twelve male elite level soccer players (mean; age: 21.8 years; height: 180.4 cm; weight: 75.7 kg) volunteered to participate in this study. Participants were from the same soccer club, covered all playing positions, and had no current injury issues. Participants performed two familiarization sessions to acquaint themselves with the device and exercise protocol. During testing, each participant performed three repetitions with 60s intra-set recovery provided. Average and peak force (N) was recorded for both limbs. Testing sessions took place on the same day and time over a two-week pre-season period and followed a full recovery day. Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV%), Minimal Detectable Change (MDC) and Typical Error (TE) were used to assess reliability. The HEL showed excellent reliability for average force (N) in the left (ICC (95% CI) = 0.9 (0.7–0.97); TE = 14.1 N, CV% = 1.87; MDC = 39.06 N) and right (ICC (95% CI) = 0.91 (0.73–0.97); TE = 20.89 N, CV% = 3.26; MDC = 57.87 N) limb, and also excellent reliability for peak force in the left (ICC (95% CI) = 0.91 (0.71–0.97); TE = 13.55 N, CV% = 1.61; MDC = 57.87 N) and right (ICC (95% CI) = 0.9 (0.7–0.97); TE = 21.70 N, CV% = 3.31; MDC = 60.11 N) limb. This data suggests the HEL as a reliable measure of both ECC hamstring strength and inter-limb asymmetries. Practitioners should consider the HEL as a reliable choice for measuring and monitoring eccentric hamstring strength in their athletes.

The association between diet in mid‐life and dementia incidence over a 20‐year period

AbstractBackgroundModifiable risk factors account for 40% of worldwide dementias. A potential modifiable risk factor for dementia and cognitive impairment is diet. However, there are conflicting results and methodological weaknesses in previous studies. The aim of this study was to investigate whether midlife diet quality is associated with subsequent risk of developing all‐cause dementia, Alzheimer’s disease (AD) or vascular dementia (VaD). In addition, the association between diet quality and future accumulation of β‐amyloid (Aβ) in cerebrospinal fluid (CSF) was examined.MethodBaseline examination within the Swedish population‐based Malmö Diet and Cancer Study (MDCS) took place between 1991‐1996 on 30,447 middle‐aged individuals. Participants from the MDCS with complete baseline dietary examination were included in this study (n=28,027) and the follow‐up for incident dementia took place until December 31, 2014. Diagnoses were collected from the Swedish National Patient Register and validated by Memory Clinic physicians. CSF Aβ42 was available in a sub‐population (n=777). Information on dietary habits was gathered through a 7‐day food diary, a detailed food frequency questionnaire and a one‐hour interview. A diet quality index was calculated from adherence to nutrition recommendations of intake of dietary fibre, added sugar, fish and shellfish, fruit and vegetables and red and processed meat (0‐5 points, poor to good). Cox proportional hazard models were used to examine associations between diet and risk of developing dementia adjusted for age, sex, education, total caloric intake and season.ResultDuring a median of 19.8 years of follow‐up, 1,943 (6.9%) participants were diagnosed with dementia. Individuals adhering to diet recommendations did not lower the risk of developing all cause dementia (HR 0.98, 95% CI 0.95‐1.02), AD (HR 0.99, 95% CI 0.95‐1.04) or VaD (HR 0.98, 95% CI 0.91‐1.06). No significant association was found between diet score and abnormal Aβ accumulation measured with CSF Aβ42 (OR 1.10, 95% CI 0.66‐1.84),Conclusion: In this long‐term prospective cohort study, adherence to dietary recommendations for fibre, sugar, fish, fruit and vegetables and red and processed meat was not significantly associated with subsequent reduced risk for developing all‐cause dementia, AD or VaD.

Modifiable factors associated with cognitive resistance in the Framingham Heart Study

AbstractBackgroundCognitive resistance to Alzheimer’s disease (AD) refers to an individual’s capacity to avoid the appearance of Alzheimer’s dementia syndrome in the context of risk factors on pathologic processes. We sought to identify associations between potential modifiable risk factors for AD and cognitive resistance.Method2,318 participants from the Offspring and Omni cohorts in Framingham Heart Study without prevalent dementia and at high risk for AD were selected. High risk for AD was defined as having ≥2 of the following risk factors measured at baseline: (1) age &gt;80 years; (2) diagnosis of cardiovascular disease or coronary heart failure; (3) carrier of ≥1 APOE ε4 allele; (4) plasma Aβ42/40 ≤0.1049 (Perez‐Grijalba et al.; 2019); (5) C‐reactive protein level ≥10 mg/L (Morley and Kushner; 1982); and (6) female sex. Cognitively resistant individuals were defined as those at high risk for AD that did not progress to a clinical diagnosis of dementia/AD. Standardized research criteria were used to ascertain all‐cause dementia and AD. Potential modifiable risk factors for AD measured at baseline included diabetes, hypertension, obesity, depression, smoking, and education. Logistic regression was used to examine associations between these factors and cognitive resistance to AD.ResultOver an average period of 36 years, absence of diabetes (OR = 3.63; 95% CI = 2.37 – 5.55; p &lt;0.001) and absence of hypertension (OR = 1.60; 95% CI = 1.02 – 2.51; p = 0.038), as well as not smoking (OR = 2.10; 95% CI = 1.41 – 3.13; p &lt;0.001), at baseline were significantly associated with cognitive resistance. Absence of depression, absence of obesity, or high education were not associated with cognitive resistance.ConclusionIndividuals at high risk for AD who do not have diabetes or hypertension, or do not smoke may be cognitively resistant to AD. These findings support the heart‐brain connection for dementia prevention and healthy cognitive aging.

Sleep-disordered breathing is independently associated with elevated natriuretic peptide levels in patients with cardiovascular diseases

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66years (55-74years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9pg/ml (23.5-146.4pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17-10.88; moderate: OR, 3.62; 95% CI 2.17-6.02; mild: OR, 2.22: 95% CI 1.42-3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD.

57 POTENTIALLY INAPPROPRIATE MEDICATION USE AND MORTALITY IN PATIENTS WITH COGNITIVE IMPAIRMENT

Abstract Background Potentially inappropriate medications (PIMs are associated with falls, hospitalisation, and cognitive decline. Few studies have investigated the association between PIMs related to cognitive impairment (PIMCog) and mortality in dementia or mild cognitive impairment (MCI). Methods This was a retrospective observational study. Patients diagnosed with MCI or dementia (DSM-IV criteria) presenting to a tertiary-referral memory clinic from 2013–2019 were eligible. The primary outcome was all-cause death. Secondary outcomes were vascular death and non-vascular death defined according to formal certification. The primary exposure variable of interest was PIMCog, defined as any medication in the Beers 2015 or STOPP criteria, classified as potentially inappropriate for patients with cognitive impairment. Anticholinergic burden was measured using the anticholinergic cognitive burden (ACB) scale. Polypharmacy was defined as ≥5 medications. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results There were 418 patients included (n = 261 dementia, n = 157 MCI). The median age was 79 (interquartile range {IQR} 74–82) and median follow-up was 809 days (IQR 552–1,571). One or more PIMCog was prescribed in 141 patients (33.4%). PIMCog use was associated with all-cause mortality after adjustment for age, sex, dementia severity, Charlson Co-morbidity Index, chronic obstructive pulmonary disease, congestive cardiac failure, and peripheral vascular disease (HR 1.96, 95% CI 1.24–3.09). PIMCog use was associated with vascular death (HR 3.28, 95% CI 1.51–7.11) but not with non-vascular death (HR 1.40 95% CI: 0.78–2.52). Neither an ACB ≥3 (HR 0.87, 95% CI: 0.46–1.64) or polypharmacy (HR 1.87, 95% CI: 0.67–5.24) were associated with death. Conclusion The burden of PIMCog use in patients with cognitive impairment is high. PIMCog use is independently associated with all-cause mortality and vascular death. This is a potential modifiable risk factor for death in patients with neurocognitive disorders. Further research is required to independently validate this finding.

High Lead Exposure Associated With Higher Blood Pressure in Haiti: a Warning Sign for Low-Income Countries.

Cardiovascular disease is the leading cause of death in lower-income countries including Haiti. Environmental lead exposure is associated with high blood pressure and cardiovascular mortality in high-income countries but has not been systematically measured and evaluated as a potential modifiable cardiovascular risk factor in lower-income countries where 6.5 billion people reside. We hypothesized lead exposure is high in urban Haiti and associated with higher blood pressure levels. Blood lead levels were measured in 2504 participants ≥18 years enrolled in a longitudinal population-based cohort study in Port-au-Prince. Lead screening was conducted using LeadCare II (detection limit ≥3.3 µg/dL). Levels below detection were imputed by dividing the level of detection by √2. Associations between lead (quartiles) and systolic blood pressure and diastolic blood pressure were assessed, adjusting for age, sex, obesity, smoking, alcohol, physical activity, income, and antihypertensive medication use. The median age of participants was 40 years and 60.1% were female. The geometric mean blood lead level was 4.73µg/dL, 71.1% had a detectable lead level and 42.3% had a blood lead level ≥5 µg/dL. After multivariable adjustment, lead levels in quartile four (≥6.5 µg/dL) compared with quartile 1 (<3.4 µg/dL) were associated with 2.42 mm Hg (95% CI, 0.36-4.49) higher systolic blood pressure and 1.96 mm Hg (95% CI, 0.56-3.37) higher diastolic blood pressure. In conclusion, widespread environmental lead exposure is evident in urban Haiti, with higher lead levels associated with higher systolic and diastolic blood pressure. Lead is a current and potentially modifiable pollutant in lower-income countries that warrants urgent public health remediation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892265.

Visual Impairment and Risk of Dementia in 2 Population-Based Prospective Cohorts: UK Biobank and EPIC-Norfolk.

Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there is a lack of large studies with objective measures of vision and with more than 10 years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk). In both cohorts, visual acuity was measured using a “logarithm of the minimum angle of resolution” (LogMAR) chart and categorized as no (≤0.30 LogMAR), mild (>0.3 to ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62 206 UK Biobank and 7 337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk, respectively, 1 113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable Cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% confidence interval [CI]: 0.92–1.72) and 2.16 (95% CI: 1.37–3.40), in UK Biobank, and 1.05 (95% CI: 0.72–1.53) and 1.93 (95% CI: 1.05–3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but was not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention; however, the possibility of reverse causation cannot be excluded.

Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization.

BackgroundLung cancer is the major cause of mortality in tumor patients. While its incidence rate has recently declined, it is still far from satisfactory and its potential modifiable risk factors should be explored.MethodsWe performed a two-sample Mendelian randomization (MR) study to investigate the causal relationship between potentially modifiable risk factors (namely smoking behavior, alcohol intake, anthropometric traits, blood pressure, lipidemic traits, glycemic traits, and fasting insulin) and lung cancer. Besides, a bi-directional MR analysis was carried out to disentangle the complex relationship between different risk factors. Inverse-variance weighted (IVW) was utilized to combine the estimation for each SNP. Cochrane’s Q value was used to evaluate heterogeneity and two methods, including MR-Egger intercept and MR-PRESSO, were adopted to detect horizontal pleiotropy.ResultsThree kinds of smoking behavior were all causally associated with lung cancer. Overall, smokers were more likely to suffer from lung cancer compared with non-smokers (OR = 2.58 [1.95, 3.40], p-value = 2.07 x 10−11), and quitting smoking could reduce the risk (OR = 4.29[2.60, 7.07], p-value = 1.23 x 10−8). Furthermore, we found a dose-response relationship between the number of cigarettes and lung cancer (OR = 6.10 [5.35, 6.96], p-value = 4.43x10-161). Lower HDL cholesterol could marginally increase the risk of lung cancer, but become insignificant after Bonferroni correction (OR = 0.82 [0.68, 1.00], p-value = 0.045). In addition, we noted no direct causal relationship between other risk factors and lung cancer. Neither heterogeneity nor pleiotropy was observed in this study. However, when treating the smoking behavior as the outcome, we found the increased BMI could elevate the number of cigarettes per day (beta = 0.139[0.104, 0.175], p-value = 1.99x10-14) and a similar effect was observed for the waist circumference and hip circumference. Additionally, the elevation of SBP could also marginally increase the number of cigarettes per day (beta = 0.001 [0.0002, 0.002], p-value = 0.018).ConclusionSmoking behavior might be the most direct and effective modifiable way to reduce the risk of lung cancer. Meanwhile, smoking behavior can be affected by other risk factors, especially obesity.

Low albumin levels are independently associated with neonatal acute kidney injury: a report from AWAKEN Study Group.

Data from adult and pediatric literature have shown an association between albumin levels and AKI. Whether hypoalbuminemia and neonatal AKI are associated has not been studied. We evaluated the association of albumin with early (during the first postnatal week) and late (after the first postnatal week) AKI for 531 neonates from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database and for 3 gestational age (GA) subgroups: < 29, 29 to < 36, and ≥ 36weeks GA. Low albumin levels were associated with increased odds of neonatal AKI; for every 0.1g/dL decrease in albumin, the odds of late AKI increased by 12% on continuous analysis. After adjustment for potential confounders, neonates with albumin values in the lowest quartiles (< 2.2g/dL) had an increased odds of early [Adjusted Odd Ratio (AdjOR) 2.5, 95% CI = 1.1-5.3, p < 0.03] and late AKI [AdjOR 13.4, 95% CI = 3.6-49.9, p < 0.0001] compared to those with albumin in the highest quartile (> 3.1g/dL). This held true for albumin levels 2.3 to 2.6g/dL for early [AdjOR 2.5, 95% CI = 1.2-5.5, p < 0.02] and late AKI [AdjOR 6.4, 95% CI = 1.9-21.6, p < 0.01]. Albumin quartiles of (2.7 to 3.0g/dL) were associated with increased odds of late AKI. Albumin levels of 2.6g/dL and 2.4g/dL best predicted early (AUC = 0.59) and late AKI (AUC = 0.64), respectively. Analysis of albumin association with AKI by GA is described. Low albumin levels are independently associated with early and late neonatal AKI. Albumin could be a potential modifiable risk factor for neonatal AKI.

Implementing a fluid volume management program to decrease intra-dialytic hypotensive events in a paediatric in-centre haemodialysis unit: a quality improvement project.

BackgroundIntra-dialytic hypotension (IDH) is the most common serious adverse event in paediatric haemodialysis (HD). Repeated IDH results in chronic multi-organ damage and increased mortality. At the Hospital for Sick Children, Toronto, retrospective data from all in-centre HD sessions revealed frequently occurring IDH events (16.5 ± 5.6% of HD sessions per week). Based on literature review and clinical expertise, fluid volume management was selected as a potential modifiable risk factor to decrease IDH. Root causes identified as contributing to IDH were incorporated into a Paediatric haemodialysis fluid volume management (PedHDfluid) program using the Model for Improvement methodology including rapid cycles of change.MethodsMultiple measures were evaluated including (i) Outcome: IDH events per number of HD sessions per week; (ii) Process: number of changes to estimated dry weight per number of HD sessions per week; (iii) Balancing: time spent on dry weight meeting per week. Data was analysed using statistical process control charts.We aimed to decrease IDH in our dialysis unit to < 10% of HD sessions per week over a 6-month period by implementing a PedHDfluid program, including a multifaceted dry weight assessment protocol, multidisciplinary meetings and electronic health records “Dry Weight Evaluation flow sheet/synopsis”.ResultsThe project resulted in a decline in IDH events from 16.5 ± 5.6% to 8.8 ± 3.3% of HD sessions per week. More frequent dry weight changes and increased awareness of fluid removal goals were noted.ConclusionsA multidisciplinary approach including regular assessment, guidelines and systematic discussion, with an embedded electronic health record assessment and data gathering tool may sustainably reduce IDH events.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information Supplementary InformationThe online version contains supplementary material available at 10.1007/s00467-021-05298-z.