Evidence for protein leverage on total energy intake, but not body mass index, in a large cohort of older adults.

BACKGROUND: Protein leverage (PL) is the phenomenon of consuming food until absolute intake of protein approaches a 'target value', such that total energy intake (TEI) varies passively with the ratio of protein: non-protein energy (fat + carbohydrate) in the diet. The PL hypothesis (PLH) suggests that the dilution of protein in energy-dense foods, particularly those rich in carbohydrates and fats, combines with protein leverage to contribute to the global obesity epidemic. Evidence for PL has been reported in younger adults, children and adolescents. This study aimed to test for PL and the protein leverage hypothesis (PLH) in a cohort of older adults. METHODS: We conducted a retrospective analysis of dietary intake in a cohort of 1699 community-dwelling older adults aged 67-84 years from the NuAge cohort. We computed TEI and the energy contribution (EC) from each macronutrient. The strength of leverage of macronutrients was assessed through power functions ( TEI = µ * EC L ). Body mass index (BMI) was calculated, and mixture models were fitted to predict TEI and BMI from macronutrients' ECs. RESULTS: In this cohort of older adults, 53% of individuals had obesity and 1.5% had severe cases. The mean TEI was 7673 kJ and macronutrients' ECs were 50.4%, 33.2% and 16.4%, respectively for carbohydrates, fat, and protein. There was a strong negative association (L = -0.37; p < 0.001) between the protein EC and TEI. Each percent of energy intake from protein reduced TEI by 77 kJ on average, ceteris paribus. However, BMI was unassociated with TEI in this cohort. CONCLUSIONS: Findings indicate clear evidence for PL on TEI, but not on BMI, likely because of aging, body composition, sarcopenia, or protein wasting.

Associations between circulating cardiovascular disease risk factors and cognitive performance in cognitively healthy older adults from the NuAge study.

Introduction: Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia. Methods: This study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points. Results: HDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males. Discussion: Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.

Multidimensional associations between nutrient intake and healthy ageing in humans.

BACKGROUND: Little is known about how normal variation in dietary patterns in humans affects the ageing process. To date, most analyses of the problem have used a unidimensional paradigm, being concerned with the effects of a single nutrient on a single outcome. Perhaps then, our ability to understand the problem has been complicated by the fact that both nutrition and the physiology of ageing are highly complex and multidimensional, involving a high number of functional interactions. Here we apply the multidimensional geometric framework for nutrition to data on biological ageing from 1560 older adults followed over four years to assess on a large-scale how nutrient intake associates with the ageing process. RESULTS: Ageing and age-related loss of homeostasis (physiological dysregulation) were quantified via the integration of blood biomarkers. The effects of diet were modelled using the geometric framework for nutrition, applied to macronutrients and 19 micronutrients/nutrient subclasses. We observed four broad patterns: (1) The optimal level of nutrient intake was dependent on the ageing metric used. Elevated protein intake improved/depressed some ageing parameters, whereas elevated carbohydrate levels improved/depressed others; (2) There were non-linearities where intermediate levels of nutrients performed well for many outcomes (i.e. arguing against a simple more/less is better perspective); (3) There is broad tolerance for nutrient intake patterns that don't deviate too much from norms ('homeostatic plateaus'). (4) Optimal levels of one nutrient often depend on levels of another (e.g. vitamin E and vitamin C). Simpler linear/univariate analytical approaches are insufficient to capture such associations. We present an interactive tool to explore the results in the high-dimensional nutritional space. CONCLUSION: Using multidimensional modelling techniques to test the effects of nutrient intake on physiological dysregulation in an aged population, we identified key patterns of specific nutrients associated with minimal biological ageing. Our approach presents a roadmap for future studies to explore the full complexity of the nutrition-ageing landscape.

Protein intake, physical activity and grip strength in European and North American community-dwelling older adults: a pooled analysis of individual participant data from four longitudinal ageing cohorts.

INTRODUCTION: Higher dietary protein, alone or in combination with physical activity (PA), may slow the loss of age-related muscle strength in older adults. We investigated the longitudinal relationship between protein intake and grip strength, and the interaction between protein intake and PA, using four longitudinal ageing cohorts. METHODS: Individual participant data from 5584 older adults (52% women; median: 75, IQR: 71.6, 79.0 years) with up to 8.5 years (mean: 4.9, SD: 2.3 years) of follow-up from the Health ABC, NuAge, LASA and Newcastle 85+ cohorts were pooled. Baseline protein intake was assessed with food frequency questionnaires and 24h recalls and categorized into <0.8, 0.8-<1.0, 1.0-<1.2 and ≥1.2 g/kg adjusted body weight (aBW)/d. The prospective association between protein intake, its interaction with PA, and grip strength (sex- and cohort-specific) was determined using joint models (hierarchical linear mixed effects and a link function for Cox proportional hazards models). RESULTS: Grip strength declined on average by 0.018 SD (95%CI: -0.026, -0.006) every year. No associations were found between protein intake, measured at baseline, and grip strength, measured prospectively, or rate of decline of grip strength in models adjusted for sociodemographic, anthropometric, lifestyle and health variables (e.g., protein intake ≥1.2 vs <0.8 g/kg aBW/d: ß= -0.003, 95%CI: -0.014,0.005 SD per year). There also was no evidence of an interaction between protein intake and PA. CONCLUSIONS: We failed to find evidence in this study to support the hypothesis that higher protein intake, alone or in combination with higher PA, slowed the rate of grip strength decline in older adults.

Methylmalonic acid analysis using urine filter paper samples to screen for metabolic vitamin B12 deficiency in older adults.

Aim: Methylmalonic acid (MMA) analysis in urine represents a noninvasive approach to screening for vitamin B12 deficiency in older adults. A method allowing the analysis of MMA/creatinine in fasting urine collected on filter paper was developed/validated. Method: Dry urine specimens were eluted using a solution containing internal standards, filtrated and analyzed by ultra-performance LC-MS/MS. Results: The method allowed the chromatographic separation of MMA from succinic acid. Dried urine samples were stable for 86 days at room temperature. The MMA/creatinine ratios measured in urine collected on filter paper were highly correlated with values derived from the corresponding liquid specimens. Conclusion: This robust filter paper method might greatly improve the accessibility and cost-effectiveness of vitamin B12 deficiency screening in older adults.

Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex.

BACKGROUND: Omega-3 (n-3) PUFAs are suggested to play a role in the prevention of cognitive decline. The evidence may be inconsistent due to methodologic issues, including interrelations with other long-chain (14 or more carbons) fatty acids (LCFAs) and use of sex as a confounding factor rather than an effect modifier. OBJECTIVES: This study evaluated the association between serum n-3 PUFAs and performance across 4 cognitive domains, overall and by sex, while controlling for other LCFAs. METHODS: In total, 386 healthy older adults (aged 77.4 ± 3.8 y; 53% females) from the Quebec Longitudinal Study on Nutrition and Successful Aging underwent a cognitive evaluation and blood sampling. Verbal and nonverbal episodic memory, executive functioning, and processing speed were evaluated. Serum LCFA concentrations were measured by gas chromatography. LCFAs were grouped according to standard fatty acid classes and factor analysis using principal component analysis (FA-PCA). Multivariate linear regression models were performed, including unadjusted and adjusted models for other LCFAs. RESULTS: Higher n-3 PUFA concentrations were associated with better nonverbal memory and processing speed in fully adjusted models not including other LCFAs (ßs of 0.21 and 0.19, respectively). The magnitude of these associations varied when other LCFAs were entered in the model (ßs of 0.27 and 0.32, respectively) or when FA-PCA factors were considered (ßs of 0.27 and 0.21, respectively). Associations with verbal episodic memory were limited to higher concentrations of EPA, whereas there was no association between n-3 PUFAs and executive functioning. Higher n-3 PUFAs were associated with better verbal and nonverbal episodic memory in females and with better executive functioning and processing speed in males. CONCLUSIONS: These results suggest that other LCFAs should be considered when evaluating the association between n-3 PUFAs and cognitive performance in healthy older adults. Sex differences across cognitive domains warrant further investigation.

Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial.

OBJECTIVE: To investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation improve cognitive performance and if apolipoprotein E (APOE) genotype or age were effect modifiers. METHODS: Healthy adults of 20 to 80 years old (n = 193) were completed a 6-month double-blind randomized controlled trial with two groups: 2.5 g/day of n-3 PUFA or a placebo. Primary outcomes were visuospatial ability and working memory and secondary outcomes were episodic memory and executive function, measured at baseline and 6 months. RESULTS: Cognitive performances did not significantly differ between groups on primary or secondary outcomes after 6 months of treatment. APOE carriers and age were not effect modifiers for any outcomes. Those with low episodic memory scores and taking the n-3 PUFA supplement, significantly improved their scores (p = 0.043). CONCLUSIONS: A 6-month n-3 PUFA supplementation did not improve cognitive performance in cognitively healthy adults and APOE status or age were not effect modifiers.

Vitamin B-12 Intake from Dairy but Not Meat Is Associated with Decreased Risk of Low Vitamin B-12 Status and Deficiency in Older Adults from Quebec, Canada.

BACKGROUND: Vitamin B-12 deficiency can result in irreversible neurologic damages. It is most prevalent among older adults (∼5%-15%), mainly due to impaired absorption. Vitamin B-12 bioavailability varies between food sources, so their importance in preventing deficiency may also vary. OBJECTIVES: Using the NuAge Database and Biobank, we examined the associations between vitamin B-12 intake (total and by specific food groups) and low vitamin B-12 status and deficiency in older adults. METHODS: NuAge-the Quebec Longitudinal Study on Nutrition and Successful Aging-included 1753 adults aged 67-84 y who were followed 4 y. Analytic samples comprised 1230-1463 individuals. Dietary vitamin B-12 intake was assessed annually using three 24-h dietary recalls. Vitamin B-12 status was assessed annually as low serum vitamin B-12 (<221 pmol/L), elevated urinary methylmalonic acid (MMA)/creatinine ratio (>2 µmol/mmol), and a combination of both (deficiency). Vitamin B-12 supplement users were excluded. Multilevel logistic regressions, adjusted for relevant confounders, were used. RESULTS: Across all study years, 21.8%-32.5% of participants had low serum vitamin B-12, 12.5%-17.0% had elevated urine MMA/creatinine, and 10.1%-12.7% had deficiency. Median (IQR) total vitamin B-12 intake was 3.19 µg/d (2.31-4.37). Main sources were "dairy" and "meat, poultry, and organ meats." The ORs (95% CIs) in the fifth quintile compared with the first of total vitamin B-12 intake were as follows: for low serum vitamin B-12, 0.52 (0.37, 0.75; P-trend < 0.0001); for elevated urine MMA/creatinine, 0.63 (0.37, 1.08; P-trend = 0.091); and for vitamin B-12 deficiency, 0.38 (0.18, 0.79; P-trend = 0.006). Similarly, ORs (95% CIs) in the fourth quartile compared with the first of dairy-derived vitamin B-12 intake were 0.46 (0.32, 0.66; P-trend < 0.0001), 0.51 (0.30, 0.87; P-trend = 0.006), and 0.35 (0.17, 0.73; P-trend = 0.003), respectively. No associations were observed with vitamin B-12 from "meat, poultry, and organ meats." CONCLUSIONS: Higher dietary vitamin B-12 intake, especially from dairy, was associated with decreased risk of low vitamin B-12 status and deficiency in older adults. Food groups might contribute differently at reducing risk of deficiency in older populations.

Milk, Yogurt, and Cheese Intake Is Positively Associated With Cognitive Executive Functions in Older Adults of the Canadian Longitudinal Study on Aging.

BACKGROUND: Dairy products provide essential nutrients such as calcium and vitamins B12 and D, and include bioactive peptides and fermented products, which may be beneficial for cognition, especially in older adults. Yet, few studies of large contemporary cohorts have investigated this relationship using sensitive domain-specific cognitive tests. METHOD: In community-dwelling older adults of the Canadian Longitudinal Study on Aging (2011-2015), we examined cross-sectional associations between total and specific dairy product intake and performance in 3 cognitive domains (executive functions, memory, and psychomotor speed). Cheese, milk, yogurt, regular-fat, low-fat, and fermented dairy product intake frequencies were estimated using a food frequency questionnaire; participants were classified into quartiles. Multivariate analyses of covariance models were applied to estimate differences. RESULTS: In 7 945 participants (65-86 years, 49% women, 97% Caucasian), the mean dairy product intake was 1.9 (1.1) times/d. Total dairy product, cheese, and low-fat dairy product intakes were positively associated with the executive function domain and yogurt intake with the memory domain (all p < .05), independently of important covariates including age, gender, education, and diet quality. Intakes of total dairy product, cheese, and low-fat dairy product were associated with verbal fluency specifically (all p < .05). Participants with a dairy product intake >2.5 times/d had a higher score compared to those consuming less. No associations were found with psychomotor speed. CONCLUSIONS: This large cohort study suggests a specific role for dairy components in executive function phonemic verbal fluency and memory. Dairy product intake, a modifiable factor, may be targeted in cognitive health-promoting interventions.

Low protein intake, physical activity, and physical function in European and North American community-dwelling older adults: a pooled analysis of four longitudinal aging cohorts.

BACKGROUND: Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking. OBJECTIVES: We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA. METHODS: We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models. RESULTS: Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g., protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: ß = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed. CONCLUSIONS: Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function.

Prospective associations of protein intake parameters with muscle strength and physical performance in community-dwelling older men and women from the Quebec NuAge cohort.

BACKGROUND: Dietary protein has been related to muscle function in aging. Beyond total intake, parameters such as protein distribution across meals might also be important. OBJECTIVES: We aimed to examine prospective associations of different protein intake parameters with muscle strength and physical performance in community-dwelling older men and women. METHODS: In total, 524 men and 574 women aged 67-84 y at baseline (T1) were followed annually for 3 y (T2, T3, T4). Outcomes included handgrip strength (kPa), knee extensor strength (kg), and physical performance (Timed Up and Go, s) at T4, and their 3-y changes (T4 minus T1). Protein intake parameters were assessed using nine 24-h recalls collected over 3 y (T1, T2, T3) and included daily total intake (g/d), number of protein-providing meals and snacks, and protein distribution across meals (expressed as CV). Associations were examined by multivariable linear regression models including all protein intake parameters simultaneously. Also, the optimal protein dose (g) per meal for the maximum effect size of total daily intake was determined. RESULTS: Higher daily protein intake was associated with better knee extensor strength and physical performance at T4 in both sexes and less physical performance decline in women. Optimal protein doses per meal were 30-35 g in men and 35-50 g in women for these outcomes. In men, more uneven protein distribution was associated with better physical performance at T4 and less handgrip strength decline. In women, a higher number of protein-providing snacks was associated with better handgrip strength and knee extensor strength at T4 and less handgrip strength decline. In neither sex was number of protein-providing meals associated with outcomes. CONCLUSIONS: Higher daily protein intake, up to 30-50 g protein/meal, may contribute to better knee extensor strength and physical performance in generally well-functioning older men and women. More aspects of protein intake may contribute to muscle strength and physical performance than solely the daily quantity, notably the protein dose per meal.

Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems.

Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with-but not definitive proof of-frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.

Sex differences in the relationship between dietary pattern adherence and cognitive function among older adults: findings from the NuAge study.

BACKGROUND: Consumption of a prudent dietary pattern rich in healthy nutrients is associated with enhanced cognitive performance in older adulthood, while a Western dietary pattern low in healthy nutrients is associated with poor age-related cognitive function. Sex differences exist in dietary intake among older adults; however, there is a paucity of research examining the relationship between sex-specific dietary patterns and cognitive function in later life. METHODS: The current study aimed to investigate sex differences in the relationship between sex-specific dietary pattern adherence and global cognitive function at baseline and over a 3-year follow-up in 1268 community-dwelling older adults (Mage = 74 years, n = 664 women, n = 612 men) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). A 78-item Food Frequency Questionnaire was used to estimate dietary intake over the previous year. Sex-specific dietary pattern scores were derived using principal component analysis. Global cognition was assessed using the Modified Mini-Mental State Examination (3MS). RESULTS: Adjusted linear mixed effects models indicated that a healthy, prudent dietary pattern was not associated with baseline cognitive performance in men or women. No relationship was found between Western dietary pattern adherence and baseline cognitive function in women. Among men, adherence to an unhealthy, Western dietary pattern was associated with poorer baseline cognitive function (ß = - 0.652, p = 0.02, 95% CI [- 1.22, - 0.65]). No association was found between prudent or Western dietary patterns and cognitive change over time in men or women. CONCLUSIONS: These findings highlight the importance of conducting sex-based analyses in aging research and suggest that the relationship between dietary pattern adherence and cognitive function in late life may be sex-dependent.

Mass spectrometry analysis of urinary methylmalonic acid to screen for metabolic vitamin B12 deficiency in older adults.

Aim: Vitamin B12 deficiency is characterized metabolically by increased serum and urine methylmalonic acid (MMA). Urinary MMA/creatinine ratio is suggested for screening for metabolic vitamin B12 deficiency in older populations. Results: A UPLC-MS/MS method for the analysis of urinary MMA and creatinine was developed/validated. A good separation of MMA from succinic acid, its structural isomer, was achieved. Intra- and interday accuracy biases and precision coefficients were all ≤6.3% for MMA and creatinine. Urine and serum samples of 34 individuals of the NuAge Biobank were analyzed for technical comparisons showing that urinary MMA/creatinine ratios by UPLC-MS/MS strongly correlated with GC-MS values, and with serum MMA values. Conclusion: The UPLC-MS/MS method developed is rapid/reliable for the analysis of urinary MMA/creatinine ratios.

Prevalence of protein intake below recommended in community-dwelling older adults: a meta-analysis across cohorts from the PROMISS consortium.

BACKGROUND: Lower protein intake in older adults is associated with loss of muscle mass and strength. The present study aimed to provide a pooled estimate of the overall prevalence of protein intake below recommended (according to different cut-off values) among community-dwelling older adults, both within the general older population and within specific subgroups. METHODS: As part of the PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) project, a meta-analysis was performed using data from four cohorts (from the Netherlands, UK, Canada, and USA) and four national surveys [from the Netherlands, Finland (two), and Italy]. Within those studies, data on protein and energy intake of community-dwelling men and women aged ≥55 years were obtained by either a food frequency questionnaire, 24 h recalls administered on 2 or 3 days, or food diaries administered on 3 days. Protein intake below recommended was based on the recommended dietary allowance of 0.8 g/kg body weight (BW)/d, by using adjusted BW (aBW) instead of actual BW. Cut-off values of 1.0 and 1.2 were applied in additional analyses. Prevalences were also examined for subgroups according to sex, age, body mass index (BMI), education level, appetite, living status, and recent weight loss. RESULTS: The study sample comprised 8107 older persons. Mean ± standard deviation protein intake ranged from 64.3 ± 22.3 (UK) to 80.6 ± 23.7 g/d [the Netherlands (cohort)] or from 0.94 ± 0.38 (USA) to 1.17z ± 0.30 g/kg aBW/d (Italy) when related to BW. The overall pooled prevalence of protein intake below recommended was 21.5% (95% confidence interval: 14.0-30.1), 46.7% (38.3-55.3), and 70.8% (65.1-76.3) using the 0.8, 1.0, and 1.2 cut-off value, respectively. A higher prevalence was observed among women, individuals with higher BMI, and individuals with poor appetite. The prevalence differed only marginally by age, education level, living status, and recent weight loss. CONCLUSIONS: In community-dwelling older adults, the prevalence of protein intake below the current recommendation of 0.8 g/kg aBW/d is substantial (14-30%) and increases to 65-76% according to a cut-off value of 1.2 g/kg aBW/d. To what extent the protein intakes are below the requirements of these older people warrants further investigation.

What do we really know about the role of caffeine on urinary tract symptoms? A scoping review on caffeine consumption and lower urinary tract symptoms in adults.

AIMS: The purpose of this scoping review was to map out the existing literature on caffeine intake and lower urinary tract symptoms (LUTS) in adults. METHODS: In this scoping review, we searched for all studies available until June 2019 in MEDLINE, Embase, CINAHL, Cochrane Central Register, PsycINFO, LILACS, LiSSa, Web of Science, and Joanna Briggs Institute electronic databases, in addition to a hand search of the bibliographies of all relevant articles and a gray literature search. Both intervention studies on the effects of caffeine reduction in adults with LUTS and observational studies on the association between caffeine intake and LUTS-related outcomes in adults were included and assessed for methodological quality by two independent reviewers. RESULTS: Fourteen intervention and 12 observational studies were included. Overall, there was a decrease in urgency episodes (level of evidence 2, grade of recommendation B) and nocturnal enuresis episodes (4, C) with caffeine reduction. Observational studies reported an unclear association between caffeine intake and LUTS-related outcomes. Most importantly, this present review highlighted high heterogeneity in the studied populations, caffeine measures, and reported outcomes. There was also unknown or high risk of bias in most identified studies. CONCLUSIONS: Caffeine reduction appears to reduce LUTS. Future studies on caffeine reduction interventions should target populations with urgency and urge urinary incontinence, which show the most promising results, and include valid and reliable measures of caffeine intake and LUTS. Finally, future studies should also use reporting guidelines to ensure lower risk of bias.

The Lost Years: Delay Between the Onset of Cognitive Symptoms and Clinical Assessment at a Memory Clinic.

BACKGROUND: Early assessment of cognitive symptoms is an issue in geriatrics. This study investigated the delay from the onset of cognitive symptoms to initial clinical assessment and its associations with patients' sociodemographic and clinical characteristics. METHODS: This is a cross-sectional retrospective study using medical chart review of 316 patients referred for assessment to a university-affiliated memory clinic. Symptom duration was self-reported by patients/carers. Severity of symptoms assessed by the MoCA and FAST instruments was compared according to delay duration (≥3 years vs. <3 years) using chi-squared tests. Logistic regression was used to determine the association between patients' characteristics and long symptom duration (≥3 years). RESULTS: At the initial assessment, 29.4% of patients reported experiencing cognitive symptoms for ≥3 years. They were more likely to have MoCA scores ≤17 (47.8 vs. 34.1%; p=.023) and FAST scores ≥5 (21.5 vs. 10.8%; p=.012). They were also significantly older than 75 years (75-84 yr: OR=2.22 [95%CI: 1.11-4.41]; ≥85 yr: 4.36 [2.08-9.11]), presented more depressive symptoms (2.37 [1.40-4.02]), and were less likely to live alone (0.55 [0.31-0.96]). CONCLUSIONS: A significant proportion of patients had cognitive symptoms for years when initially assessed, which delayed diagnosis and management. Stigma, depression, and compensatory help from carers may contribute to this delay.

Food avoidance in patients with inflammatory bowel disease: What, when and who?

BACKGROUND & AIMS: Patients with inflammatory bowel diseases avoid a variety of foods. However, it remains unclear how this behavior varies across patients. This cross-sectional study investigated how the food avoidance pattern in inflammatory bowel disease varies according to disease's activity, disease's subtype, Crohn's location, and prior history of bowel resection, strictures, and fistulae. METHODS: Outpatients with Crohn's disease (n = 173) and ulcerative colitis (n = 72) reported which food they avoid when they perceive they are in remission or in active disease using a list of 82 food items classified in 10 categories. Medical charts were reviewed for patients' characteristics. Linear regression analyses were used to compare food exclusion rates between patients' subgroups and food categories. RESULTS: During remission, food exclusion rates varied from 1 to 39%. Most avoided foods were those with capsaicin, meat alternatives, and raw vegetables. Overall, food exclusion rates were 38% higher in Crohn's disease than ulcerative colitis (P < 0.001), and 50% higher in stricturing than non-stricturing Crohn's disease (P < 0.001). During active disease, food exclusion rates were 69% higher than in remission (P < 0.001). Similar differences between subgroups were again observed during active disease though less noticeable than in remission. No association was found with other disease characteristics. Avoided foods were very similar across patients except for alcoholic beverages and foods rich in dietary fibers/residue, which were avoided more specifically during active disease and in Crohn's disease, respectively. CONCLUSIONS: Food avoidance is common among patients with inflammatory bowel diseases, and most particularly in those with stricturing Crohn's disease. Specificities in avoidance pattern suggest that the clinical response to dietary restrictions may differ according to the disease's characteristics.

Association Between Metformin Adherence and All-Cause Mortality Among New Users of Metformin: A Nested Case-Control Study.

BACKGROUND: Metformin presents better survival rates than other oral antidiabetics in the treatment of type 2 diabetes. However, these benefits may be dampened by inadequate treatment adherence. OBJECTIVE: We aimed to investigate the relationship between adherence level to metformin therapy and all-cause mortality over 10 years in incident metformin users. METHODS: A nested case-control study was conducted using a large cohort of beneficiaries of the Quebec public drug insurance plan, aged 45 to 85 years, who initiated metformin between 2000 and 2009. Each case of all-cause death during follow-up was matched with up to 10 controls. Adherence to metformin was measured using the medication possession ratio (MPR). Conditional logistic regression models were used to estimate rate ratios (RRs) for mortality between adherent (MPR ≥ 80%) and nonadherent patients (MPR < 80%). Subgroup analyses were conducted according to age (45-64 and 65-85 years) and comedication use (antihypertensive/cardiovascular drugs and statins). RESULTS: The cohort included 82 720 incident metformin users, followed up for 2.4 [0.8-4.4] years (median [interquartile range]) and 4747 cases of all-cause deaths. Analyses revealed decreased mortality risks after long-term adherence to metformin. Specifically, RRs were 0.84 (95% CI = [0.71-0.98]) and 0.69 [0.57-0.85] after 4 to 6 and ≥6 years of adherence to metformin, respectively. Survival benefits of long-term adherence (≥4 years) were also observed across most subgroups and particularly in patients using neither antihypertensive/cardiovascular drugs nor statins (0.57 [0.41-0.77]). CONCLUSIONS: Long-term adherence to metformin is associated with decreased risks of all-cause mortality in incident metformin users. Further research should investigate whether survival benefits vary according to the comorbidity burden of patients.

Increase in Psychoactive Drug Prescriptions in the Years Following Autism Spectrum Diagnosis: A Population-Based Cohort Study.

BACKGROUND: Psychoactive medications are commonly prescribed to autistic individuals, but little is known about how their use changes after diagnosis. OBJECTIVES: This study describes the use of psychoactive drugs in children and young adults newly diagnosed with autism spectrum, between the year before and up to 5 years after diagnosis. METHODS: Multivariable logistic regression was used to examine the relationship between the use psychoactive drugs before the first diagnosis of autism spectrum condition (from 1998 to 2010), and the clinical and demographic characteristics, identified from public health care databases in Quebec. The types of drugs prescribed and psychoactive polypharmacy were evaluated over 5 years of follow-up. Generalized estimating equations (GEE) were used to examine the association of age and time with the use of psychoactive drugs. RESULTS: In our cohort of 2,989 individuals, diagnosis of another psychiatric disorder before autism spectrum strongly predicted psychoactive drug use. We observed that the proportion of users of psychoactive drugs increased from 35.6% the year before, to 53.2% 5 years after the autism spectrum diagnosis. Psychoactive polypharmacy (≥2 psychoactive drug classes) also increased from 9% to 22% in that time. Age and time since diagnosis strongly associated with the types and combinations of psychoactive drugs prescribed. CONCLUSIONS: Psychoactive drug use and polypharmacy increases substantially over time after autism spectrum disorder diagnosis in children.