Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia.

BACKGROUND: Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia. METHODS: Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3-4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. RESULTS: Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively). CONCLUSIONS: High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03056508 .

Vitamin K status and inflammation are associated with cognition in older Irish adults.

Studies have shown associations between reduced vitamin K status and poor cognitive function. However, despite this apparent link, direct studies measuring cognitive function, vitamin K status and inflammation are lacking. In the current study, The ELDERMET cohort was investigated to identify associations between cognition, vitamin K status and inflammation. The primary aim of the ELDERMET study was to investigate the relationship between gut bacteria, diet, lifestyle and health in 500 older Irish adults. Significant differences in serum phylloquinone, dietary phylloquinone and inflammatory markers were found across varying levels of cognitive function, after controlling for sex, age, body mass index (BMI), triglycerides and blood pressure. In addition, significantly higher levels of dietary phylloquinone were found in those with better cognition compared to those with the poorest function. Higher levels of inflammatory were also associated with poor cognition. Furthermore, both dietary and serum phylloquinone were significant independent predictors of good cognitive function, after controlling for confounders. This study highlights the importance of dietary vitamin K as a potentially protective cognitive factor; it also provides evidence for the correlation between cognition and inflammation. Strategies should be devised by which elderly populations can access rich dietary sources of phylloquinone to maintain cognition.

Production of photoionized plasmas in the laboratory with x-ray line radiation.

In this paper we report the experimental implementation of a theoretically proposed technique for creating a photoionized plasma in the laboratory using x-ray line radiation. Using a Sn laser plasma to irradiate an Ar gas target, the photoionization parameter, ξ=4πF/N_{e}, reached values of order 50ergcms^{-1}, where F is the radiation flux in ergcm^{-2}s^{-1}. The significance of this is that this technique allows us to mimic effective spectral radiation temperatures in excess of 1 keV. We show that our plasma starts to be collisionally dominated before the peak of the x-ray drive. However, the technique is extendable to higher-energy laser systems to create plasmas with parameters relevant to benchmarking codes used to model astrophysical objects.

Chronic perfusion of angiotensin II causes cognitive dysfunctions and anxiety in mice.

High blood pressure is a major risk factor in the onset of cerebrovascular diseases and cognitive impairment. However, mechanisms by which these occur remain unclear and treatments are, therefore, ineffective to prevent cognitive decline related to cardiovascular diseases. Angiotensin II is a peptide involved in the onset and maintenance of hypertension and its effect on cognition was studied acutely but never chronically. Hence, the aim of this study is to evaluate whether chronic hypertensive levels of angiotensin II infusion alter cognitive functions in C57BL6 mice. In this study we used subcutaneous mini-pumps containing a concentration of angiotensin II (1900 ng/kg/min) that induces malignant hypertension or a saline solution for 14 and 21 days. Blood pressure was carefully monitored by a non-invasive tail-cuff method every week throughout the experiment. Spatial memory was assessed using the Morris water maze test and anxiety was measured by the elevated plus maze and the open field tests. The results indicate learning and spatial memory deficit as well as an anxious behavior induced by angiotensin II, in comparison to the vehicle group, starting at the 3rd week of perfusion. The motricity and visual acuity were equivalent in angiotensin II perfused mice compared to their respective control. These results suggest a strong relationship between angiotensin II and the development of cognitive dysfunctions and anxiety along with sustained high blood pressure.

Neurovascular deconvolution of optical signals as a proxy for the true neuronal inputs.

UNLABELLED: Since the Kalman filter and Monte Carlo techniques, much theoretical work has been put into the development of signal deconvolution tools. Among recent developments taking place in neuroscience are Dynamic Expectation Maximization, Generalized Filtering and the Cubature Kalman Filter. While there are exciting prospects to use these tools for Dynamic Causal Modeling and other analyses of networks, there has been comparatively little work to validate the algorithms on controlled experimental data. In this work, the latest evolution of these tools, the square-root cubature Kalman smoother (SCKS), is tested for its effectiveness on multimodal neurovascular data. Multispectral intrinsic optical imaging and electrophysiological measurements of Wistar rats are used in combination with somatosensory stimulation. The Buxton-Friston (B-F) balloon model is then deconvolved with the SCKS algorithm to obtain the estimated neuronal inputs u(t) from the hemodynamic measurements (flow, oxy- and deoxygenated hemoglobin). RESULTS: The estimated neuronal inputs are compared to the stimulation protocol and a sensitivity and specificity analysis is carried out. SCKS succeeds in recovering most of the stimulations. Next, the estimated inputs are compared to actual measures of neuronal activity: local field potentials (LFPs) and multiunit activity (MUA). Good sensitivity of the technique is obtained with both LFPs and MUA over the whole recordings, with the area of the ROC curves favoring LFPs. A weak correlation between SCKS estimated inputs and LFPs is found outside stimulation periods, significant at one standard deviation. Finally, the accuracy of state reconstructions is studied and SCKS reconstructed states are highly concordant with measured states.

The impact of recent advances in laboratory astrophysics on our understanding of the cosmos.

An emerging theme in modern astrophysics is the connection between astronomical observations and the underlying physical phenomena that drive our cosmos. Both the mechanisms responsible for the observed astrophysical phenomena and the tools used to probe such phenomena-the radiation and particle spectra we observe-have their roots in atomic, molecular, condensed matter, plasma, nuclear and particle physics. Chemistry is implicitly included in both molecular and condensed matter physics. This connection is the theme of the present report, which provides a broad, though non-exhaustive, overview of progress in our understanding of the cosmos resulting from recent theoretical and experimental advances in what is commonly called laboratory astrophysics. This work, carried out by a diverse community of laboratory astrophysicists, is increasingly important as astrophysics transitions into an era of precise measurement and high fidelity modeling.

Biophysical model estimation of neurovascular parameters in a rat model of healthy aging.

Neuronal, vascular and metabolic factors result in a deterioration of the cerebral hemodynamic response with age. The interpretation of neuroimaging studies in the context of aging is rendered difficult due to the challenge in untangling the composite effect of these modifications. In this work we integrate multimodal optical imaging in biophysical models to investigate vascular and metabolic changes occurring in aging. Multispectral intrinsic optical imaging of an animal model of healthy aging, the LOU/c rat, is used in combination with somatosensory stimulation to study the modifications of the hemodynamic response with increasing age. Results are fitted with three macroscopic biophysical models to extract parameters, providing a phenomenological description of vascular and metabolic changes. Our results show that 1) biophysical parameters are estimable from multimodal data and 2) parameter estimates in this population change with aging.

Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: a model of healthy aging.

The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

The evolution of nutritional status of geriatric patients without cachexia is associated with food intake in sub-acute care.

OBJECTIVES: To determine if changes in patients' nutritional status during hospitalization are related to daily energy and protein intakes when cachectic/inflammatory conditions are controlled for. DESIGN: Prospective study. SUBJECTS: A total of 32 non-cachectic patients (21 women; 65-92 y). METHODS: Nutritional status was evaluated at admission and discharge using the Protein-Energy Malnutrition Index which includes BMI, %IBW, TS, MAC, albumin, hemoglobin and lymphocyte count. Food intake was assessed 3 meals/day every other day for an average of 46.2 +/- 14.6 meals/participant. RESULTS: In all, 47% of the study sample was malnourished at admission. Nutritional status improved in 73% of patients who had been identified as malnourished and in 30 % of non-malnourished patients at admission. Total energy intake correlated with improvements in BMI, %IBW and total lymphocyte count (all p < 0.04). Improvement in PEMI score for the whole group was associated with functional status (p < 0.05). Controlling for this variable, energy (kj/kg body weight) and protein (g/kg body weight) intakes correlated positively with improvements in BMI, %IBW and MAC (Energy: partial r = 0.644, 0.624, 0.466 respectively; Protein: partial r = 0.582, 0.554, 0.433 respectively; all p < 0.05). CONCLUSIONS: Results from this study offer strong evidence that when cachectic/inflammatory conditions are controlled for, standard nutrition care is compatible with the maintenance or improvement of nutritional status during the hospital stay.

Nutritional implications of patient-provider interactions in hospital settings: evidence from a within-subject assessment of mealtime exchanges and food intake in elderly patients.

OBJECTIVE: To examine the nutritional implications of the interactions taking place between patients and care providers during mealtimes in hospital settings. Specifically, we tested research propositions that the amount and nature of interpersonal behaviours exchanged between patients and providers impact patients' food intake. These propositions were derived from prior evidence of social influences on eating behaviour and a well-established framework that identifies two fundamental modalities of human interaction: striving for mastery and power (agency) and efforts to promote union with others (communion). DESIGN: In a within-subject naturalistic study, participants were observed on multiple meals (n=1477, 46.2 meals/participant on average), during which participants' and providers' agency- and communion-related behaviours and patients' protein and energy intake were recorded. Meal-level frequency and complementarity of patients' and providers' behaviours were computed to test research propositions. SETTING: Dining room of a geriatric rehabilitation unit. SUBJECTS: Thirty-two elderly patients (21 females, mean age:78.8, 95% CI: 76.4, 81.1). RESULTS: Meal-level frequency of patient-provider exchanges (P=0.016) and patients' agency-related behaviours (P=0.029), as well as mutual reciprocation of patients' and providers' communion-related behaviours (P=0.015) on a given meal were positively linked to protein intake. Higher energy intake was found during meals where patients expressed more agency-related behaviours (P=0.029). CONCLUSION: Results present evidence that the amount and nature of patient-provider interpersonal exchanges on a given meal influence the nutritional quality of food intake in hospitalized elderly. They provide insights into how to improve the design and delivery of routine care to this malnutrition-prone population. SPONSORSHIP: This study was supported by the Canadian Institutes of Health Research (Operating grant to Laurette Dubé, Doctoral Fellowship to Catherine Paquet) the Fonds de la Recherche en santé du Québec and by the Danone Institute (Doctoral fellowship to Danielle St-Arnaud McKenzie).

Effects of dietary restriction and metal supplementation on the accumulation of iron-laden glial inclusions in the aging rat hippocampus.

The mechanisms responsible for the pathological deposition of iron and other redox-active metals in the aging and degenerating mammalian CNS remain poorly understood. We previously demonstrated that normal aging and pharmacological (oxidative) stressors promote the transformation of astroglial mitochondria to iron-laden, diaminobenzidine (DAB)-positive cytoplasmic inclusions in sub-cortical regions of the rat brain. In the current study, we demonstrate that (1) numbers of DAB-positive glial granules in the rat dorsal hippocampus, an area implicated in learning and memory, progressively increase between 3, 12 and 22 months of age; (2) dietary restriction (40%), a manipulation that attenuates many mammalian aging processes, has no effect on the age-related accumulation of these gliosomes in the rat hippocampus; and (3) the latter can be accelerated by dietary supplementation of iron and copper. Our data support the view that dietary exposure to iron and/or copper in adult life can impact the sequestration of redox-active metals in aging hippocampal astroglia.

Determinants of diet quality among Quebecers aged 55-74.

OBJECTIVES: Sociodemographic, lifestyle and dietary characteristics were studied to gain insights into determinants of total diet quality and diversity in a weighted sample of 460 participants aged 55-74 (53% female) from the 1990 Enqu te qu b coise sur la nutrition (EQN) dataset. METHODS: Dietary data consisted of an interviewer-administered 24-hour recall and food frequency questionnaire, and a self-administered questionnaire on dietary behaviours, attitudes and perceptions. 24-hour recall data were coded into food groups as described in Canada's Food Guide for Healthy Eating. Diet quality was scored using the categorical Dietary Diversity Score (DDS, range 0-4) and continuous Dietary Adequacy Score (DAS, range 0-18). A second nonconsecutive recall (10% of subjects) permitted correction of food group portions for intraindividual variability and subsequent calculation and validation of usual DDS and DAS. Relationships were examined between the scores and independent variables. Forward leastwise logistic regession (DDS) and stepwise multiple regression (DAS) analyses were conducted with independent variables showing significant bivariate relationships. RESULTS: Among men, breakfast consumption and eating commercially-prepared meals were positively associated with usual DDS, but poor social support and supplement use negatively predicted this score. Eating fewer than 3 meals daily, smoking, and dietary supplement use were negative predictors of usual DAS (r2=0.155). Among women, eating commercial foods was a negative predictor of usual DDS, as was preferring overweight to depriving themselves of favourite foods. Reporting that health concerns influenced food choices and disagreeing with the statement that effort is needed to have a nice body were positive determinants of usual DAS in women. On the other hand, eating fewer than 3 meals daily negatively predicted this dietary index (r2 = 0.162). CONCLUSIONS: Gender differences in predictors of diet quality suggest the need to target nutrition health promotion to the needs of older men and women to encourage optimal eating habits.

Employee reactions to the introduction of a bulk food distribution system in a nursing home.

Decentralized bulk food distribution was implemented in a nursing home. Employees working with elderly residents with dementia were asked their opinion of the impact of the new system on residents and workload. A convenience sample of 24 employees (57% of the staff) completed a 31-item, self-administered Likert-scale questionnaire that allowed open-ended comments. Responses were subjected to descriptive quantitative analysis, and a qualitative approach was used to explore themes that emerged in comments. Qualitative analysis indicated that 52% of responses were negative in tone, 30% were positive, and 18% were neutral. Initially, three categories of comments emerged, with specific multiple themes related to the residents (41%), the employees (37%), or the food-service system (22%). Most comments in the employee category were negative, and suggested that the decentralized food-service system caused hardship for the staff. This problem was resolved by adding one staff-hour at the midday meal. One year later, an abbreviated repeat survey of 29 employees revealed adaptation and general acceptance of the system. Because a motivated patient care staff is essential to the successful feeding of nursing home residents with dementia, employees' concerns must be considered when operational changes are planned.

Absence of nutritional or clinical consequences of decentralized bulk food portioning in elderly nursing home residents with dementia in Montreal.

OBJECTIVES: To evaluate the nutritional and clinical consequences of changing from a centralized food delivery system to decentralized bulk food portioning; a system in which meal portioning occurs on residents' floors of a nursing home. DESIGN: A pilot study with a pre-post design SUBJECTS/SETTING: The study took place on one floor of a home for elderly persons with dementia. Of the 34 residents, 22 (1 man) participated in this study. Average age was 82 years (range = 55 to 94 years). Nutritional status was verified before introduction of the bulk food portioning system by 3 nonconsecutive days of observed food intakes, anthropometric measurements (height, weight, triceps skinfold thickness, mid-upper-arm circumference), and biochemical parameters (albumin, lymphocytes, glucose, sodium, potassium, transferrin, vitamin B-12, folate, hemoglobin). Trained dietitians collected the dietary and anthropometric data and validated the food intake estimates and anthropometric measurements. Data were also collected 10 weeks after implementation of the new food distribution system. STATISTICAL ANALYSES PERFORMED: Paired t tests adjusted by a Bonferroni correction assessed differences between values measured before and after introduction of the new food distribution system. RESULTS: Average food consumption increased substantially and significantly after introduction of the bulk food portioning system. Mean energy intakes rose from 1,555 to 1,924 kcal/day and most other nutrients also increased, many significantly, but there were no changes in anthropometric values or biochemical parameters, except for albumin level which decreased to the lower normal limit. APPLICATIONS: Portioning of food in the residents' dining room simulates a homelike atmosphere thereby encouraging increased food consumption. With well-trained and enthusiastic staff, this system could contribute to improved nutritional status in the very elderly, even those who have dementia. Dietitians have a key role to play in overseeing residents' nutritional needs and in training, supervising, and motivating foodservice personnel.

Relationship of plasma carotenoids, retinol and tocopherols in mothers and newborn infants.

OBJECTIVE: We studied the relationship between maternal and cord plasma concentrations of carotenoids, retinol, and tocopherols in normal mother-baby pairs. METHODS: Healthy pregnant women (n = 10) were recruited at a Montréal hospital. Venous blood samples were collected from the mothers at delivery and cord blood was obtained immediately post partum from the umbilical vein after clamping of the cord. All deliveries were full term deliveries and all babies had normal birth weights. Maternal and umbilical cord blood samples were handled identically. Plasma was digested with lipase and plasma carotenoids were extracted and measured using HPLC. RESULTS: Cord plasma concentration of carotenoids were significantly lower than that of maternal plasma (p < 0.001). There was a high correlation of lutein (r = 0.889, p = 0.006) and cryptoxanthin (r = 0.912, p = 0.0002) between maternal plasma concentrations and cord plasma concentrations. The concentrations of the hydrocarbon carotenoids, alpha-carotene and beta-carotene, were also correlated (r = 0.779, p = 0.0133, & r = 0.782, p = 0.0076, respectively) between maternal plasma and cord plasma. Whereas the plasma concentration of the acyclic carotenoid, lycopene, showed no correlation between the two groups, after adjustment for plasma triglycerides, the lycopene correlation between maternal and cord plasma was the highest (r = 0.975, p = 0.0001) of all the carotenoids tested. Cord plasma retinol concentration, which was 50% of that of maternal plasma, was also found to have no correlation with that of maternal plasma. Plasma concentration of alpha-tocopherol showed no correlation between two groups, whereas there was high correlation between cord and maternal gamma-tocopherol concentrations (r = 0.808, p = 0.0047). CONCLUSION: The nutritional status of mothers affects the nutritional status of their babies for certain fat soluble nutrients.

The vitamin K-dependent proteins: an update.

Historically known for its role in blood coagulation, vitamin K also has been shown to be required for the physiologic activation of numerous proteins that are not involved in hemostasis. Over the last 20 years, vitamin K-dependent proteins have been isolated in bone, cartilage, kidney, atheromatous plaque, and numerous soft tissues. Although the precise mechanism of action of many of these proteins remains to be determined, their discovery has proven important from a physiologic point of view.

Long-term calorie restriction protects rat pituitary growth hormone-releasing hormone binding sites from age-related alterations.

In mammals, middle age and late adulthood is characterized by a decrease of growth hormone (GH) secretion and insulin-like growth factor 1 (IGF-1) serum levels, contributing to tissue and organ atrophy. This condition is related, at least in part, to alterations of pituitary GH-releasing hormone (GHRH) receptor-binding sites. Prevention of age-related deterioration of tissues and organs, retardation of the onset or progression of a wide range of age-related diseases and extension of both mean and maximum life span can be achieved through life-long moderate calorie restriction (CR). Because CR has been reported to positively modulate the somatotropic axis resulting in the maintenance of a youthful GH secretory pattern in aged rats, we investigated whether or not benefits of a long-term (10 months) 40% CR, started in 8-month-old male Sprague-Dawley rats, was accomplished by preventing age-related alterations of pituitary GHRH receptor binding sites. We also studied whether or not a short-term (50 days) 40% CR, started in 16-month-old rats, could revert them. Potential hormonal and metabolic modulators of the GHRH receptors were investigated as well. GHRH binding parameters were derived from saturation studies performed in pituitary homogenates with [125I-Tyr10]hGHRH (1-44)NH2. As previously reported, the high affinity GHRH receptor-binding sites were blunted in 18-month-old ad libitum-fed rats and the apparent concentration of total binding sites was reduced. Short-term CR neither restored high affinity GHRH binding sites nor increased the apparent concentration of total binding sites. On the contrary, long-term calorie-restricted 18-month-old rats exhibited high and low affinity GHRH binding sites (Kd1: 1.73 +/- 0.35 nM; Kd2: 310 +/- 41 nM; Bmax1: 183 +/- 55 fmol/mg protein; Bmax2: 30 +/- 3 pmol/mg protein) as found in 2-month-old rats (Kd1: 0.68 +/- 0.15 nM; Kd2: 350 +/- 47 nM; Bmax1: 219 +/- 53 fmol/mg protein; Bmax2: 84 +/- 9 pmol/mg protein). Our results imply that CR must be implemented before age-related alterations of GHRH receptor-binding sites become too severe or that CR has to be carried out for a long period of time, independently from the age at which it begins. Protection of pituitary GHRH binding sites from age-related alterations could not be attributed to changes in circulating levels of total or free T4 or free fatty acids. Finally, the anti-aging effect of a long-term CR observed at the level of pituitary GHRH receptors does not result in a significant increase of total IGF-1 circulating levels. Identification of molecular and cellular mechanisms responsible for these actions will deserve attention in order to identify centrally and/or peripherally active classes of molecules that could preserve, in aging mammals, the functionality of the somatotropic axis through selective regulation of pituitary GHRH receptors.

Lymphatic absorption of retinol in young, mature, and old rats: influence of dietary restriction.

Earlier studies have shown that hepatic vitamin A stores increase with age and that rats subjected to life-long dietary restriction (DR) have greater hepatic retinoid concentrations than ad libitum-fed rats. It was suggested that these changes may be attributed to altered intestinal absorption, and so we measured retinol absorption in 3, 12, and 22 month-old female Sprague-Dawley rats fed ad libitum (AL) or a restricted diet (40%) enriched (DR+) or not (DR) with vitamins and minerals. An in vivo model was used and lymph collected from the mesenteric duct while rats were infused a micellar solution containing [3H]retinol into the proximal duodenum. Aging significantly decreased lymph flow, and at all ages DR and DR+ rats exhibited a higher flow than age-matched AL rats. Absorption of retinol was not significantly modified by age in AL and DR+ rats. However, in the DR group, there was a marked decrease in absorption between 3 and 12 months of age. Retinol absorption was significantly higher in 12 and 22 month-old DR+ rats than in age-matched AL rats, a finding that may be explained by both higher lymph flow rate and higher long-term vitamin A intake per body weight. In conclusion, the increased content of vitamin A in the livers of older AL rats is not associated with changes in intestinal absorption. In DR rats, however, retinoid accumulation in the liver may be explained by increased intestinal absorption of the vitamin, though other mechanisms may be involved. A possible explanation may be a decreased output of retinol from the liver as a result of lower metabolic needs. The lower serum vitamin A concentrations observed in DR rats would tend to support this hypothesis.