Flavonoid intake and risk of Parkinson's disease.

BACKGROUND: Flavonoids have been proposed to reduce the risk of Parkinson's disease (PD). However, results from epidemiological studies have been inconclusive. OBJECTIVE: To prospectively examine the association between the intake of flavonoids and their subclasses and the risk of PD and how pesticides may confound or modify that association. METHODS: The study population comprised 80 701 women (1984-2016) and 48 782 men (1986-2016) from two large US cohorts. Flavonoid intake was ascertained at baseline and every 4 years thereafter using a semiquantitative Food Frequency Questionnaire. We conducted multivariable-adjusted Cox regression models to estimate HRs and 95% CIs of PD according to quintiles of baseline and cumulative average intakes of flavonoids and subclasses. We repeated the analyses, adjusting for intakes of high-pesticide-residue fruits and vegetables (FVs) and stratifying by servings/day of high-pesticide-residue FV intake. RESULTS: We identified 676 incident PD cases in women and 714 in men after 30-32 years of follow-up. Higher total flavonoid intake at baseline was not associated with a lower PD risk, neither in men (HR comparing highest to lowest quintile: 0.89, 95% CI: 0.69 to 1.14) nor in women (HR comparing highest to lowest quintile: 1.27, 95% CI: 0.98 to 1.64). Similar results were observed for cumulative average intakes and flavonoid subclasses. Results remained similar after adjustment for and stratification by high-pesticide-residue FV and when analyses were restricted to younger PD cases. CONCLUSION: These results do not support a protective effect of flavonoid intake on PD risk. Pesticide residues do not confound or modify the association.

Frailty and Other Factors Associated With Early Outcomes in Middle-to Older Age Trauma Patients: A Prospective Cohort Study.

OBJECTIVES: To prospectively investigate associations of frailty and other predictor variables with functional recovery and health outcomes in middle-aged and older patients with trauma. DESIGN: Single-center prospective cohort study. SETTING: Emergency department of Wan Fang Hospital in Taiwan. PARTICIPANTS: Trauma patients aged 45 and older. MEASUREMENTS: Frailty was assessed with the Clinical Frailty Scale (CFS). Injury mechanisms, pre-existing diseases, and fracture locations were recorded at baseline. The primary outcome was functional recovery assessed using the Barthel Index (BI). Secondary outcomes were new care needs, unscheduled return visits, and falls 3 months postinjury. RESULTS: A total of 588 participants were included in the final analysis. For every one-point increase in the CFS, the multivariable-adjusted odds ratio (OR, 95% confidence interval [CI]) of failure to retain the preinjury BI was 1.34 (1.16-1.55); associations were consistent across levels of age and injury severities. Significant joint associations of frailty and age with poor functional recovery were observed. CFS was also associated with new care needs (OR for every one-point increase, 1.36, 95% CI, 1.17-1.58), unscheduled return visits (OR 1.26, 95% CI, 1.04-1.51), and falls (OR 1.23, 95% CI, 1.01-1.51). Other variables associated with failure to retain preinjury BI included road traffic accident and presence of hip fracture. CONCLUSION: Frailty was significantly associated with poor functional and health outcomes regardless of injury severity in middle-aged and older patients with trauma. Injury mechanisms and fracture locations were also significant predictors of functional recovery postinjury.

Long-term intake of total energy and fat in relation to subjective cognitive decline.

Diet is one of the modifiable risk factors for cognitive decline. However, human studies on total energy intake and cognitive function have remained limited and studies on fat intake and cognitive decline have been inconclusive. We aimed to examine prospectively the associations between long-term intakes of total energy and fat with subsequent subjective cognitive decline (SCD). A total of 49,493 women from the Nurses' Health Study and 27,842 men from the Health Professionals Follow-up Study were followed for over 20 years. Average dietary intake was calculated based on repeated food frequency questionnaires (SFFQs), and Poisson regression was used to evaluate associations. Higher total energy intake was significantly associated with greater odds of SCD in both cohorts. Comparing the highest with lowest quintiles of total energy intake, the pooled multivariable-adjusted ORs (95% CIs) for a 3-unit increment in SCD, corresponding to poor versus normal SCD, was 2.77 (2.53, 2.94). Each 500 kcal/day greater intake of total energy was associated with 48% higher odds of SCD. Intakes of both total fat and total carbohydrate appeared to contribute to the positive association between total energy intake and SCD although for the same percent of energy, the association was stronger for total fat. In conclusion, higher intakes of total energy, total fat, and total carbohydrate were adversely associated with SCD. Whether these associations are causal is unclear and deserves further investigation.

Spinal cord injury and Alzheimer's disease risk: a population-based, retrospective cohort study.

STUDY DESIGN: Propensity score-matched, retrospective cohort study. OBJECTIVES: To determine the risk of developing Alzheimer's disease (AD) in patients with spinal cord injury (SCI). SETTING: The present study used Taiwan's National Health Insurance Research Database. METHODS: A total of 9257 patients who had ⩾2 ambulatory visits with a diagnosis of SCI in 2001 were included in the SCI group. The non-SCI group consisted of 37,028 propensity score-matched patients without a diagnosis of SCI. The cumulative incidence of AD was estimated for each of the two patient groups using the Kaplan-Meier method. Stratified Cox proportional hazard regression was then employed to assess the influence of SCI on the risk of AD. RESULTS: During the follow-up period, 25 subjects in the SCI group and 57 in the non-SCI group developed AD. The cumulative incidence of AD in the SCI group was higher than in the non-SCI group (P = 0.0168); and the hazard ratio of AD for the SCI group, as compared to the non-SCI group, was 1.71 (95% CI 1.06-2.76, P = 0.0273). CONCLUSIONS: This study suggests that patients with SCI have an increased risk of developing AD.

Reliability and validity of the Taiwan Chinese version of the Lower Extremity Functional Scale.

BACKGROUND/PURPOSE: The Lower Extremity Functional Scale (LEFS) is a region-specific functional outcome measure designed for patients with lower extremity musculoskeletal dysfunction. In this study, a Taiwan Chinese version was adapted and its validity and reliability were tested. METHODS: The LEFS questionnaire was adapted and tested in 159 patients with lower extremity disorders from two university hospitals. The Cronbach α-coefficient value was calculated for internal consistency. Intraclass correlation coefficient (ICC), Bland-Altman plot, and minimal detectable change (MDC) were used for evaluating the test-retest reliability and agreement in 40 patients followed up within 7 days. Construct and convergent/divergent validity were examined by principal component analysis and correlation was examined with the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. RESULTS: The internal consistency and test-retest reliability of the adapted LEFS questionnaire were satisfactory [Cronbach α: 0.98; ICC(2,1), 0.97]. The Bland-Altman plot of the two tests showed a relatively consistent distribution, with limits of agreement in the range of -9.32 to 13.02. The MDC at 90% confidence interval was 9.6. One-factor model was confirmed by principal component analysis. Also, there was a moderate association between the LEFS and the physical component scores and several subscales of SF-36, but not with the mental component scores. CONCLUSION: The Taiwan Chinese version of the LEFS questionnaire is a valid and reliable measure of health status for patients with lower extremity disorders.

Occupational lead exposure and survival with amyotrophic lateral sclerosis.

Objective: Lead exposure has been hypothesized to increase the risk of ALS, but only two studies have examined the association with ALS survival, and with inconsistent results. The use of occupational history to assess lead exposure can avoid reverse causation that may occur in epidemiologic analyses that use biomarkers of lead exposure collected after ALS onset.Methods: We evaluated the relationship of occupational lead exposure to ALS survival among 135 cases from an international ALS cohort that included deep phenotyping, careful follow-up, and questionnaires to quantify participants' occupation history. ALS patients were recruited in 2015-2019. We determined occupational lead exposure using a job-exposure matrix. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for survival using Cox proportional hazard analysis with adjustment for covariates.Results: A total of 135 ALS patients completed the environmental questionnaires, among whom 38 reached a survival endpoint (death or permanent assisted ventilation). The median survival was 48.3 months (25th-75th percentile, 30.9-74.1). Older patients and those with initial symptom other than limb onset had shorter survival time. There were 36 ALS cases with occupational lead exposure. After adjusting for age, sex, site of onset, smoking, and military service, lead exposure was associated with an HR of 3.26 (95%CI 1.28-8.28). Results with adjustment for subsets of these covariates were similar.Conclusions: These results suggest that lead exposure prior to onset of ALS is associated with shorter survival following onset of ALS, and this association is independent of other prognostic factors.

Kidney function, albuminuria, and their modification by genetic factors and risk of incident dementia in UK Biobank.

BACKGROUND: Associations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR). However, whether there is a graded increase in dementia risk for worse eGFR in each ACR category is unclear. Also, whether genetic risk for dementia impacts the associations is unknown. The current study aims to investigate the associations between eGFR and albuminuria with dementia risk both individually and jointly, whether the associations vary by different follow-up periods, and whether genetic factors modified the associations. METHODS: In 202,702 participants aged ≥ 60 years from the UK Biobank, Cox proportional-hazards models were used to examine the associations between eGFR and urine albumin creatinine ratio (ACR) with risk of incident dementia. GFR was estimated based on serum creatinine, cystatin C, or both. The models were restricted to different follow-up periods (< 5 years, 5-10 years, and ≥ 10 years) to investigate potential reverse causation. RESULTS: Over 15 years of follow-up, 6,042 participants developed dementia. Decreased kidney function (eGFR < 60 ml/min/1.73m2) was associated with an increased risk of dementia (Hazard Ratio [HR] = 1.42, 95% Confidence Interval [CI] 1.28-1.58), compared to normal kidney function (≥ 90 ml/min/1.73m2). The strength of the association remained consistent when the models were restricted to different periods of follow-up. The HRs for incident dementia were 1.16 (95% CI 1.07-1.26) and 2.24 (95% CI 1.79-2.80) for moderate (3-30 mg/mmol) and severely increased ACR (≥ 30 mg/mmol) compared to normal ACR (< 3 mg/mmol). Dose-response associations were observed when combining eGFR and ACR, with those in the severest eGFR and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34-9.43). APOE status significantly modified the association (p = 0.04), with stronger associations observed among participants with a lower genetic risk of dementia. There was no evidence of an interaction between kidney function and non-APOE polygenic risk of dementia with dementia risk (p = 0.42). CONCLUSIONS: Kidney dysfunction and albuminuria were individually and jointly associated with higher dementia risk. The associations were greater amongst participants with a lower genetic risk of dementia based on APOE, but not non-APOE polygenic risk.

Prediction of posttraumatic functional recovery in middle-aged and older patients through dynamic ensemble selection modeling.

Introduction: Age-specific risk factors may delay posttraumatic functional recovery; complex interactions exist between these factors. In this study, we investigated the prediction ability of machine learning models for posttraumatic (6 months) functional recovery in middle-aged and older patients on the basis of their preexisting health conditions. Methods: Data obtained from injured patients aged ≥45 years were divided into training-validation (n = 368) and test (n = 159) data sets. The input features were the sociodemographic characteristics and baseline health conditions of the patients. The output feature was functional status 6 months after injury; this was assessed using the Barthel Index (BI). On the basis of their BI scores, the patients were categorized into functionally independent (BI >60) and functionally dependent (BI ≤60) groups. The permutation feature importance method was used for feature selection. Six algorithms were validated through cross-validation with hyperparameter optimization. The algorithms exhibiting satisfactory performance were subjected to bagging to construct stacking, voting, and dynamic ensemble selection models. The best model was evaluated on the test data set. Partial dependence (PD) and individual conditional expectation (ICE) plots were created. Results: In total, nineteen of twenty-seven features were selected. Logistic regression, linear discrimination analysis, and Gaussian Naive Bayes algorithms exhibited satisfactory performances and were, therefore, used to construct ensemble models. The k-Nearest Oracle Elimination model outperformed the other models when evaluated on the training-validation data set (sensitivity: 0.732, 95% CI: 0.702-0.761; specificity: 0.813, 95% CI: 0.805-0.822); it exhibited compatible performance on the test data set (sensitivity: 0.779, 95% CI: 0.559-0.950; specificity: 0.859, 95% CI: 0.799-0.912). The PD and ICE plots showed consistent patterns with practical tendencies. Conclusion: Preexisting health conditions can predict long-term functional outcomes in injured middle-aged and older patients, thus predicting prognosis and facilitating clinical decision-making.

Long-term dietary protein intake and subjective cognitive decline in US men and women.

BACKGROUND: Diet is one of the modifiable risk factors for cognitive decline. However, studies on dietary protein intake and cognitive decline have remained limited and inconclusive. OBJECTIVES: In this study, we aimed to investigate the associations between long-term dietary protein intake and subsequent subjective cognitive decline (SCD). METHODS: We included 49,493 women from the Nurses' Health Study (NHS) (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (HPFS) (1986-2002). For the NHS, average dietary intake was calculated from 7 repeated semi-quantitative FFQs (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012. Poisson regression was used to examine the associations between dietary protein, amino acids, and various protein food sources with subsequent SCD. RESULTS: Higher protein intake compared with total carbohydrates was associated with lower odds of SCD. When substituting 5% energy from protein for the equivalent percentage of energy from total carbohydrates, the pooled multivariable-adjusted ORs (95% CIs) were 0.89 (0.85, 0.94) for total protein, 0.89 (0.84, 0.94) for animal protein, and 0.74 (0.62, 0.88) for plant protein. When substituting 5% of energy from animal protein with plant protein, the OR was 0.84 (95% CI: 0.72, 0.97). For protein food sources, higher intakes of beans/legumes, fish, and lean poultry were significantly associated with lower odds of SCD, but higher intake of hotdogs was associated with higher odds of SCD. CONCLUSIONS: Higher protein intake was associated with lower odds of SCD when compared isocalorically with carbohydrate. Plant protein sources were also associated with lower odds when compared with animal protein sources. Our findings suggest that adequate protein intake, and choices of protein sources could play a role in the maintenance of cognition and should be studied further.

Intake of Flavonoids and Flavonoid-Rich Foods and Mortality Risk Among Individuals With Parkinson Disease: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Although flavonoids have the potential to exert neuroprotective benefits, evidence of their role in improving survival rates among individuals with Parkinson disease (PD) remains lacking. We aimed to prospectively study the association between prediagnosis and postdiagnosis flavonoid intakes and risk of mortality among individuals with PD identified from 2 large ongoing cohorts of US men and women. METHODS: Included in the current analysis were 599 women from the Nurses' Health Study and 652 men from the Health Professionals Follow-Up Study who were newly diagnosed with PD during follow-up. Dietary intakes of total flavonoid and its subclasses, together with major flavonoid-rich foods (tea, apples, berries, orange and orange juice, and red wine), were repeatedly assessed with a validated food frequency questionnaire every 4 years. Mortality was ascertained via the National Death Index and state vital statistics records. RESULTS: We documented 944 deaths during 32 to 34 years of follow-up. A higher total flavonoid intake before PD diagnosis was associated with a lower future risk for all-cause mortality in men (hazard ratio [HR] comparing 2 extreme quartiles 0.53, 95% confidence interval [CI] 0.39, 0.71; p for trend < 0.001) but not in women (HR 0.93, 95% CI 0.68, 1.28; p for trend = 0.69) after adjustment for age, smoking status, total energy intake, and other covariates. The pooled HR comparing the extreme quartiles was 0.70 (95% CI 0.40, 1.22; p for trend = 0.25) with significant heterogeneity (p = 0.01). For flavonoid subclasses, the highest quartile of anthocyanins, flavones, and flavan-3-ols intakes before diagnosis had a lower mortality risk compared to the lowest quartile (pooled HR 0.66, 0.78, and 0.69, respectively; p < 0.05 for all); for berries and red wine, participants consuming ≥3 servings per week had a lower risk (pooled HR 0.77, 95% CI 0.58, 1.02; and pooled HR 0.68, 95% CI 0.51, 0.91, respectively) compared to <1 serving per month. After PD diagnosis, greater consumptions of total flavonoid, subclasses including flavonols, anthocyanins, flavan-3-ols, and polymers, and berries and red wine were associated with lower mortality risk (p < 0.05 for all). DISCUSSION: Among individuals with PD, higher consumption of flavonoids, especially anthocyanins and flavan-3-ols, and flavonoid-rich food such as berries and red wine was likely to be associated with a lower risk of mortality.

Pulsed wave Doppler ultrasonography for the assessment of peripheral vasomotor response in an elderly population.

PURPOSE: To assess sympathetic vasomotor activity and its changes with age, using pulsed wave Doppler ultrasound. METHODS: We recruited 20 young adults (24-37 years old) and 20 older individuals (60-81 years old). Pulsed wave Doppler ultrasound was applied over the right radial artery to measure blood flow at rest and after a voluntary inspiratory cough eliciting sympathetic activation. The maximal (Vmax), minimal (Vmin), time-averaged (TAMaxV) blood flow velocity, and the pulsatility index (PI) were calculated and compared between groups. RESULTS: At rest, PI was similar in both groups but Vmax and TAMaxV were higher in the older group (p < 0.05). Vmax, Vmin, and TAMaxV decreased, and PI increased after inspiratory cough in both groups (p ≤ 0.001), but this increase was lower in the older group (p < 0.001). TAMaxV after coughing was higher in the older group (p < 0.05). Heart rate did not differ significantly within or between groups. CONCLUSIONS: The older group exhibited reduced vasomotor reactivity of the radial artery after sympathetic stimulus. Peripheral vasomotor response should be interpreted with caution in elderly populations.

Application of pulsed-wave Doppler ultrasound to exploration of the peripheral vasomotor response by gender and hand dominance.

PURPOSE: Laser Doppler flowmetry measures peripheral vasomotor response but fails to detect changes in vascular diameters, resistance, and heart rates. Because this response contributes to assessing sympathetic disorders and relies on the above variables to be correctly interpreted, we used pulsed-wave Doppler (PWD) ultrasound to evaluate the response and to determine whether it was affected by gender or hand dominance. METHODS: PWD was applied to bilateral deep palmar branches of the radial arteries of 22 men and 22 women, using post-inspiratory cough as the sympathetic stimulus. Pulsatility index (PI), arterial diameters, heart rates, flow velocity, and blood flow before and after sympathetic stimuli were analyzed for both groups. RESULTS: Women had a higher PI value of the radial arteries at rest; in contrast, that of men was higher after sympathetic stimuli. Blood flow velocity (V max, V max mean, and V mean) at rest was higher for men than for women. A significant difference was observed in V min after stimulus. Arterial diameters and blood flow before and after stimuli were higher for men than for women. Post-inspiratory cough caused significant diameter reduction in women but heart rate elevation in men. Hand dominance had no effect. CONCLUSIONS: This study demonstrated the suitability of PWD for detailing peripheral vasomotor response, which was affected by gender but not hand dominance. Our results suggest application of PWD to diseases with unilateral sympathetic impairment, but responses for different sexes should be treated with caution.

Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women.

OBJECTIVE: To prospectively examine the associations between long-term dietary flavonoids and subjective cognitive decline (SCD). METHODS: We followed 49,493 women from the Nurses' Health Study (NHS) (1984-2006) and 27,842 men from the Health Professionals Follow-Up Study (HPFS) (1986-2002). Poisson regression was used to evaluate the associations between dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subsequent SCD. For the NHS, long-term average dietary intake was calculated from 7 repeated semiquantitative food frequency questionnaires (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012. RESULTS: Higher intake of total flavonoids was associated with lower odds of SCD after adjustment for age, total energy intake, major nondietary factors, and specific dietary factors. In a comparison of the highest vs the lowest quintiles of total flavonoid intake, the pooled multivariable-adjusted odds ratio (OR) of 3-unit increments in SCD was 0.81 (95% confidence interval [CI] 0.76, 0.89). In the pooled results, the strongest associations were observed for flavones (OR 0.62 [95% CI 0.57, 0.68]), flavanones (0.64 [0.58, 0.68)]), and anthocyanins (0.76 [0.72, 0.84]) (p trend <0.001 for all groups). The dose-response curve was steepest for flavones, followed by anthocyanins. Many flavonoid-rich foods such as strawberries, oranges, grapefruits, citrus juices, apples/pears, celery, peppers, and bananas, were significantly associated with lower odds of SCD. CONCLUSION: Our findings support a benefit of higher flavonoid intakes for maintaining cognitive function in US men and women.

Estimating Life Expectancy and Lifetime Healthcare Costs for Alzheimer's Disease in Taiwan: Does the Age of Disease Onset Matter?

BACKGROUND: People with early onset Alzheimer's disease (EOAD) seem to suffer greater impact. But there is a lack of population-based studies on loss of life expectancy (LE) and lifetime healthcare costs. OBJECTIVES: We conducted this study to estimate LE, expected years of life lost (EYLL), and lifetime healthcare costs for Alzheimer's disease (AD) in Taiwan stratified by onset age and gender, using a method which integrates the product of the survival function and the mean cost function over a lifetime horizon. METHODS: We linked the National Health Insurance datasets with the National Mortality Registry and extrapolated the survival to lifetime to estimate the mean cumulative costs since the date of the first AD diagnosis using medical claims between 2001 and 2012. RESULTS: A total of 21,615 mild to moderate AD patients (including 20,358 late-onset (LOAD) and 1,257 EOAD) were recruited. The average onset age for EOAD was 61 years old, while that of LOAD was 78. Although the LE of EOAD was 4.8 years longer than that of LOAD due to younger age, the EYLL for the former was 8.7 years versus 1.7 years for the latter. EOAD also had higher lifetime healthcare costs than the LOAD group (USD$37,957±2,403 versus 33,809±786). CONCLUSIONS: Since EOAD patients had both higher EYLL and lifetime healthcare costs than LOAD, future studies should pay more attention to the needs of EOAD patients.

Responsiveness of SF-36 and Lower Extremity Functional Scale for assessing outcomes in traumatic injuries of lower extremities.

OBJECTIVE: To assess the responsiveness of one generic questionnaire, Medical Outcomes Study Short Form-36 (SF-36), and one region-specific outcome measure, Lower Extremity Functional Scale (LEFS), in patients with traumatic injuries of lower extremities. DESIGN: A prospective and observational study of patients after traumatic injuries of lower extremities. Assessments were performed at baseline and 3 months later. SETTING: In-patients and out-patients in two university hospitals in Taiwan. PARTICIPANTS: A convenience sample of 109 subjects were evaluated and 94 (86%) were followed. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Assessments of responsiveness with distribution-based approach (effect size, standardized response mean [SRM], minimal detectable change) and anchor-based approach (receiver's operating curve analysis, ROC analysis). RESULTS: LEFS and physical component score (PCS) of SF-36 were all responsive to global improvement, with fair-to-good accuracy in discriminating between participants with and without improvement. The area under curve gained by ROC analysis for LEFS and SF-36 PCS was similar (0.65 vs. 0.70, p=0.26). CONCLUSIONS: Our findings revealed comparable responsiveness of LEFS and PCS of SF-36 in a sample of subjects with traumatic injuries of lower limbs. Either type of functional measure would be suitable for use in clinical trials where improvement in function was an endpoint of interest.