Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones ...derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels.
In general, preparations of coffee, teas, and cocoa containing high levels of polyphenols, L-theanine and other bioactive compounds selectively enhance mood and cognition effects of caffeine. This ...review summarizes the bioactive components of commonly consumed natural caffeine sources (e.g. guayusa, mate and camellia teas, coffee and cocoa) and analyzes the psychopharmacology of constituent phytochemicals: methylxanthines, polyphenols, and L-theanine. Acute and chronic synergistic effects of these compounds on mood and cognition are compared and discussed. Specific sets of constituent compounds such as polyphenols, theobromine and L-theanine appear to enhance mood and cognition effects of caffeine and alleviate negative psychophysiological effects of caffeine. However, more research is needed to identify optimal combinations and ratios of caffeine and phytochemicals for enhancement of cognitive performance.
•Coffee, tea, mate, guayusa, and cocoa contain various beneficial phytochemicals•Methylxanthine + phytochemical interactions often superior to caffeine alone•Numerous positive effects on mood and cognition, both acutely and chronically•L-theanine and polyphenols such as flavonoids and chlorogenic acids most promising•Available research requires replication; longitudinal cohort studies still missing
Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 ...prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as < 45 years (early menopause), 45-49, 50-51 (reference category), 52-53, 54-55, and ≥ 56 years (late age at menopause). We used multinomial logistic regression models to estimate multi variable relative risk ratios (RRRs) and 95% confidence intervals (CI) for the associations between BMI and age at menopause. The mean (standard deviation) age at menopause was 51.4 (3.3) years, with 2.5% of the women having early and 8.1% late menopause. Compared with those with normal BMI (18.5-24.9 kg/m²), underweight women were at a higher risk of early menopause (RRR 2.15, 95% CI 1.50-3.06), while overweight (1.52, 1.31-1.77) and obese women (1.54, 1.18-2.01) were at increased risk of late menopause. Overweight and obesity were also significantly associated with around 20% increased risk of menopause at ages 52-53 and 54-55 years. We observed no association between underweight and late menopause. The risk of early menopause was higher among obese women albeit not significant (1.23, 0.89-1.71). Underweight women had over twice the risk of experiencing early menopause, while overweight and obese women had over 50% higher risk of experiencing late menopause.
Food preferences are often modified in populations during stressful, unanticipated events. We examined how a U.S. population's food choices changed during the beginning of the COVID-19 stay-at-home ...orders, specifically during the spring of 2020.
Daily dietary intake data from a digital behavior change weight loss program, which includes an interface for logging meals, beverages, and snacks, were analyzed to assess self-reported food choices from March 5-March 11, 2020 ("Start-COVID") and during the first week of the COVID-19 lockdown (March 12-March 18, 2020; "during-COVID"). The final sample consisted of 381,564 participants: 318,076 (83.4%) females, the majority who were aged 45–65 years (45.2%). Results indicate that self-reported servings of fresh fruit and vegetable intake decreased from start-to during-COVID, while intake of red meat and starchy vegetables increased. More men than women increased their intake of red meat and processed meat. Less overall change in fruit and vegetable consumption was seen in those 66 and older, compared to aged 18–35. Lean meat and starchy vegetable intake increased in older participants, but the change was negligible in younger subjects. More subjects aged 18–35 years reduced their intake of caffeine, desserts, lean meat, and salads compared to older participants. No changes were observed in snack or alcohol intake logged.
This study revealed that particular food groups were altered according to age and gender during the first weeks of COVID lockdown. Understanding changes in food choices during a crisis may be useful for preparing supply chains and public health responses.
•Growing evidence suggests that food preferences and consumption behaviors are modified in populations during stressful events.•Self-reported servings of fresh fruit and vegetable intake decreased from pre-to during-COVID, while intake of red meat and starchy vegetables increased.•More men than women increased their intake of red meat and processed meat.•Less overall change in fruit and vegetable consumption was seen in those 66 and older, compared to aged 18–35.•More subjects aged 18–35 years reduced their intake of caffeine, desserts, lean meat and salads compared to older participants.
Little is known about the acute precipitants of ischemic stroke, although evidence suggests infections contribute to risk. We hypothesized that acute hospitalization for infection is associated with ...the short-term risk of stroke.
The case-crossover design was used to compare hospitalization for infection during case periods (90, 30, or 14 days before an incident ischemic stroke) and control periods (equivalent time periods exactly 1 or 2 years before stroke) in the Cardiovascular Health Study, a population-based cohort of 5888 elderly participants from 4 US sites. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. Confirmatory analyses assessed hazard ratios of stroke from Cox regression models, with hospitalization for infection as a time-varying exposure.
During a median follow-up of 12.2 years, 669 incident ischemic strokes were observed in participants without a baseline history of stroke. Hospitalization for infection was more likely during case than control time periods; for 90 days before stroke, OR=3.4 (95% CI, 1.8 to 6.5). The point estimates of risks were higher when we examined shorter intervals: for 30 days, OR=7.3 (95% CI, 1.9 to 40.9), and for 14 days, OR=8.0 (95% CI, 1.7 to 77.3). In survival analyses, risk of stroke was associated with hospitalization for infection in the preceding 90 days, adjusted hazard ratio=2.4 (95% CI, 1.6 to 3.4).
Hospitalization for infection is associated with a short-term increased risk of stroke, with higher risks observed for shorter intervals preceding stroke.
Frequent and severe vasomotor symptoms during menopause are linked with adverse health outcomes. Understanding modifiable lifestyle factors for the risk of vasomotor menopausal symptoms is important ...to guide preventive strategies.
We investigated the associations between body mass index and smoking, their joint effects with the risk of vasomotor symptoms, and whether the associations differed by menopausal stage.
The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events pooled data on 21,460 midlife women from 8 studies (median age, 50 years; interquartile range, 49–51 years) for the cross-sectional analysis. Four studies provided data for the prospective analysis (n=11,986). Multinomial logistic regression models with 4 categories of frequency/severity for the outcome of vasomotor symptoms were used to estimate relative risk ratios and 95% confidence intervals that were adjusted for within-study correlation and covariates.
At baseline, nearly 60% of the women experienced vasomotor symptoms. One-half of them were overweight (30%) or obese (21%), and 17% were current smokers. Cross-sectional analyses showed that a higher body mass index and smoking more cigarettes with longer duration and earlier initiation were all associated with more frequent or severe vasomotor symptoms. Never smokers who were obese had a 1.5-fold (relative risk ratio, 1.52; 95% confidence interval, 1.35–1.73) higher risk of often/severe vasomotor symptoms, compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of often/severe vasomotor symptoms was much greater among smokers who were obese (relative risk ratio, 3.02; 95% confidence interval, 2.41–3.78). However, smokers who quit at <40 years of age were at similar levels of risk as never smokers. Prospective analyses showed a similar pattern, but the association attenuated markedly after adjustment for baseline vasomotor symptoms. Furthermore, we found that the association between body mass index and vasomotor symptoms differed by menopausal status. Higher body mass index was associated with increased risk of vasomotor symptoms in pre- and perimenopause but with reduced risk in postmenopause.
High body mass index (≥25 kg/m2) and cigarette smoking substantially increased women’s risk for experiencing frequent or severe vasomotor symptoms in a dose-response manner, and smoking intensified the effect of obesity. However, the effect of body mass index on the risk of vasomotor symptoms was opposite among postmenopausal women. Maintaining a normal weight before the menopausal transition and quitting smoking at <40 years of age may mitigate the excess risk of vasomotor symptoms in midlife.
Over the past decade, there has been increasing interest in the role of serotonin 6 (5-HT6) receptors in higher cognitive processes such as memory. Polymorphisms of the 5-HT6 receptor have been ...implicated in syndromes that affect cognition, such as schizophrenia and dementia. Manipulation of 5-HT6 receptor activity alters the transmission of several neurotransmitters important in memory: acetylcholine and glutamate, as well as dopamine, ã-aminobutyric acid (GABA), epinephrine (E), and norepinephrine (NE). Several 5-HT6 antagonists have been developed, advancing the understanding of the relationship between 5-HT6 blockade and memory consolidation in diverse learning paradigms. There is also evidence that 5-HT6 receptor activity affects anxiety behaviors and may be involved in the pathophysiology of schizophrenia. Several clinically useful atypical antipsychotics and antidepressants have 5-HT6 affinity, but recently developed selective 5-HT6 receptor antagonists may present attractive, new therapeutic options for several types of disease states.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood ...and the role of sleep difficulties in both directions.
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49-51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
At baseline, the prevalence of VMS (40%, range 13-62%) and depressed mood (26%, 8-41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27-1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47-2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90-1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38-2.34).
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
Little is known about nutritional factors during weight loss on digital commercial weight loss programs. We examined how nutritional factors relate to weight loss for individuals after 4 and 18 ...months on a mobile commercial program with a food categorization system based on energy density (Noom). This is a two-part (retrospective and cross-sectional) cohort study. Two time points were used for analysis: 4 months and 18 months. For 4-month analyses, current Noom users who met inclusion criteria (n = 9880) were split into 5% or more body weight loss and stable weight loss (0 ± 1%) groups. Individuals who fell into one of these groups were analyzed at 4 months (n = 3261). For 18-month analyses, individuals from 4-month analyses who were still on Noom 18 months later were invited to take a one-time survey (n = 803). At 18 months 148 participants were analyzed. Noom has a system categorizing foods as low-, medium-, and high-energy-dense. Measures were self-reported proportions of low-, medium-, and high-energy-dense foods, and self-reported nutritional factors (fruit and vegetable intake, dietary quality, nutrition knowledge, and food choice). Nutritional factors were derived from validated survey measures, and food choice from a novel validated computerized task in which participants chose a food they would want to eat right now. ANOVAs compared participants with 5% or more body weight loss and participants with stable weight (0 ± 1%) at 4 months on energy density proportions. Analyses at 18 months compared nutritional factors across participants with >10% (high weight loss), 5–10% (moderate weight loss), and less than 5% body weight loss (low weight loss), and then assessed associations between nutritional factors and weight loss. Individuals with greater weight loss reported consuming higher proportions of low-energy-dense foods and lower proportions of high-energy-dense foods than individuals with less weight loss at 4 months and 18 months (all ps < 0.02). Individuals with greater weight loss had higher fruit and vegetable intake (p = 0.03), dietary quality (p = 0.02), nutrition knowledge (p < 0.001), and healthier food choice (p = 0.003) at 18 months. Only nutrition knowledge and food choice were associated with weight loss at 18 months (B = −19.44, 95% CI: −33.19 to −5.69, p = 0.006; B = −5.49, 95% CI: −8.87 to −2.11, p = 0.002, respectively). Our results highlight the potential influence of nutrition knowledge and food choice in weight loss on a self-managed commercial program. We also found for the first time that in-the-moment inclination towards food even when just depicted is associated with long-term weight loss.
The contribution of 100% fruit juice (FJ) to the total daily intakes of energy, sugars, and select vitamins and minerals and to the recommended dietary allowances (RDAs) or adequate intake (AI) of ...these micronutrients was assessed in individuals reporting the consumption of 100% FJ in the national dietary intake surveys of the United States (U.S.;
= 8661), the United Kingdom (UK;
= 2546) and Brazil (
= 34,003). Associations of 100% FJ intake with the odds of being overweight or obese also were assessed. Data from the U.S. National Health and Nutrition Examination Survey (2013-2014), the UK National Diet and Nutrition Survey (2012-2014), and Brazil's Pesquisa de Orçamentos Familiares (2008-2009) were used, and all analyses were limited to individuals reporting consumption of 100% FJ on at least one day of the dietary intake survey. Approximately 34%, 37%, and 42% of individuals surveyed reported the consumption of 100% FJ on at least one day of the dietary intake survey in the U.S., UK, and Brazil, respectively, and the average daily intakes of 100% FJ were 184 g, 130 g, and 249 g, respectively. Across the 3 countries, 100% FJ contributed to 3-6% of total energy intakes, 12-31% of total sugar intakes, 21-54% of total vitamin C intakes, 1-12% of total vitamin A intakes, 4-15% of total folate intakes, 7-17% of total potassium intakes, 2-7% of total calcium intakes, and 4-12% of total magnesium intakes. In a multivariate logistic regression model, juice intake was associated with a significant reduction in the odds of being overweight or obese in UK adults (OR = 0.79; 0.63, 0.99), and significant increases in the odds of being overweight or obese in UK children (OR = 1.16; 1.01, 1.33) and Brazilian adults (OR = 1.04; 1.00, 1.09). Nutrient contributions of 100% FJ vary according to regional intake levels. In all three countries studied, 100% FJ contributed to more than 5% of the RDAs for vitamin C and folate. In the U.S. and Brazil, 100% FJ contributed to more than 5% of the RDA for magnesium and more than 5% of the AI for potassium.