A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment.

INTRODUCTION: White matter (WM) energy supply is crucial for axonal function and myelin maintenance. An exogenous source of ketones, the brain's alternative fuel to glucose, bypasses the brain's glucose-specific energy deficit and improves cognitive outcomes in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in specific WM fascicles in MCI has not previously been reported. METHODS: This 6-month interventional study included MCI participants randomized to a placebo (n = 16) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre- and post-intervention. WM fascicle uptake of ketone and glucose and structural properties were assessed using positron emission tomography and diffusion imaging, respectively. RESULTS: Ketone uptake was increased in the kMCT group by 2.5- to 3.2-fold in all nine WM fascicles of interest (P < .001), an effect seen both in deep WM and in fascicle cortical endpoints. Improvement in processing speed was positively associated with WM ketone uptake globally and in individual fascicles, most importantly the fornix (r = +0.61; P = .014). DISCUSSION: A 6-month kMCT supplement improved WM energy supply in MCI by increasing ketone uptake in WM fascicles. The significant positive association with processing speed suggests that ketones may have a role in myelin integrity in MCI.

Statin use moderates the beneficial effects of aerobic exercise on older adults' performances on the Stroop test: A subanalysis.

Aerobic training can lead to improved cognition in older adults and this effect can be explained by enhanced cardiorespiratory fitness. However, statins could limit the physical benefits of aerobic training by altering the mechanisms through which exercise improves cognition. Whether statins could have an effect on the cognitive benefits associated with aerobic training remains to be elucidated. The objective of this study was to determine whether the cognitive benefits of aerobic training were comparable in statin users and non-users. A total of 144 sedentary participants (>60 y.o.; 106 non-users, 38 statin users) were included. Participants were either part of an aerobic training group (n = 75) or a control group (n = 69). Cognition was assessed using the Stroop test. Analyses were performed on z-score changes from pre to post-intervention of Stroop reaction time (RT) and number of errors, using Two-factor ANCOVAs, while controlling for potential confounding factors (age, education, BMI, Charlson Comorbidity Index, sex, protocol and handgrip strength). The moderating effect of statins on the cognitive changes associated with aerobic training was determined through moderation analyses. An interaction effect on the Stroop switching condition was detected between intervention and statin intake (F [1, 140] = 5.659, P < 0.01). The intervention effect on switching RT was moderated by statin intake, where intervention improved switching RT only in non-users (Effect = 0.1678; P < 0.01). Statins could limit the cognitive benefits of aerobic training on switching capacities in some patients. Future randomized studies including a larger number of participants and looking at different types of statins should be conducted to confirm these results.

A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT.

INTRODUCTION: Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI). METHODS: Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44). RESULTS: Free and cued recall (Trial 1; P = .047), verbal fluency (categories; P = .024), Boston Naming Test (total correct answers; P = .033), and the Trail-Making Test (total errors; P = .017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre-intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged. CONCLUSIONS: This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease.

Physical Exercise Training Effect and Mediation Through Cardiorespiratory Fitness on Dual-Task Performances Differ in Younger-Old and Older-Old Adults.

OBJECTIVE: It has often been reported that dual-task (DT) performance declines with age. Physical exercise can help improve cognition, but these improvements could depend on cognitive functions and age groups. Moreover, the mechanisms supporting this enhancement are not fully elucidated. This study investigated the impacts of physical exercise on single- and dual-task performance in younger-old (<70) and older-old (70+) adults. The study also assessed whether the training effect on cognition was mediated by improvement in cardiorespiratory fitness. METHODS: One hundred forty-three participants (65-89 years) took part in a physical exercise intervention for 3 months or were assigned to a control group. All participants completed a DT paradigm and an estimated measure of cardiorespiratory fitness. Regression models were used to test the training effect on these outcomes, and mediation analyses were used to determine whether the training-related cognitive changes were mediated by changes in cardiorespiratory fitness. RESULTS: In 70+, training predicted improved processing speed (ßc = -.33) and cardiorespiratory fitness (ßa = .26) and the effect of training on processing speed was fully mediated by change in cardiorespiratory fitness (ßab = -.12). In <70, training predicted improvement in task-set cost (ßc = -.26) and change in cardiorespiratory fitness (ßa = .30) but improvement in task-set cost was not entirely mediated by change in cardiorespiratory fitness. DISCUSSION: Results are discussed in terms of the mechanisms supporting DT performance improvement following physical exercise training in older adults.

A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment.

INTRODUCTION: Unlike for glucose, uptake of the brain's main alternative fuel, ketones, remains normal in mild cognitive impairment (MCI). Ketogenic medium chain triglycerides (kMCTs) could improve cognition in MCI by providing the brain with more fuel. METHODS: Fifty-two subjects with MCI were blindly randomized to 30 g/day of kMCT or matching placebo. Brain ketone and glucose metabolism (quantified by positron emission tomography; primary outcome) and cognitive performance (secondary outcome) were assessed at baseline and 6 months later. RESULTS: Brain ketone metabolism increased by 230% for subjects on the kMCT (P < .001) whereas brain glucose uptake remained unchanged. Measures of episodic memory, language, executive function, and processing speed improved on the kMCT versus baseline. Increased brain ketone uptake was positively related to several cognitive measures. Seventy-five percent of participants completed the intervention. DISCUSSION: A dose of 30 g/day of kMCT taken for 6 months bypasses a significant part of the brain glucose deficit and improves several cognitive outcomes in MCI.

Investigating dose-response effects of multimodal exercise programs on health-related quality of life in older adults.

BACKGROUND: Older adults are at risk of multiple chronic diseases, most of which could be prevented by engaging in regular physical activity. Frailty is a state of increased vulnerability to diseases. Worsening symptoms of frailty, such as decrease in physical functionality, can compromise health-related quality of life (HR-QOL). Previous findings suggest that frailty moderates the relationship between physical activity and HR-QOL, yet intervention findings are limited, particularly in dose-response analyses. Hence, this study was conducted to test if lower-dose physical activity (120 minutes/week) would provide the same benefits in health outcomes (physical functionality and HR-QOL) as higher-dose physical activity (180 minutes/week). METHODS: Participants (n=110) were older adults comprising higher-dose, lower-dose, and control groups who were combined from recent randomized controlled trials. Experimental groups participated in a multimodal exercise program in a supervised laboratory setting for 12 weeks. RESULTS: The higher-dose group showed a significant improvement in physical functionality (ß=0.23, P=0.03) and in overall HR-QOL (ß=0.44, P=0.001) including its subcategories over the control group. A group × frailty interaction revealed that frail individuals significantly improved in capacity HR-QOL when they exercised at a higher dose (F (1, 49)=4.57, P=0.038). CONCLUSION: This study identifies a positive, predictive relationship between exercise duration and health outcomes (HR-QOL dimensions and frailty) among older adults. Frail individuals in the higher-dose group demonstrated significant recovery of capacity HR-QOL, thus reflecting improvement in their daily activities.

Smart Home Technology: A New Approach for Performance Measurements of Activities of Daily Living and Prediction of Mild Cognitive Impairment in Older Adults.

BACKGROUND: Functional assessment is of paramount importance when mild cognitive impairment is suspected, but common assessment tools such as questionnaires lack sensitivity. An alternative and innovative approach consists in using sensor technology in smart apartments during scenario-based assessments of instrumental activities of daily living (IADL). However, studies that investigate this approach are scarce and the technology used is not always transposable in healthcare settings. OBJECTIVE: To explore whether simple and wireless technology used in two different smart environments could add value to performance and rater-based measures of IADL when it comes to predicting mild cognitive impairment (MCI) in older adults. METHODS: Twenty-six (26) cognitively healthy older adults (CH) and 22 older adults with MCI were recruited. Functional performance in a set of five scripted tasks was evaluated with sensor-based observations (motion, contact, and electric sensors) and performance-based measures (rated with videotapes). The five tasks could be performed in any order and were detailed on an instruction sheet given to participants. RESULTS: Sensor-based observations showed that participants with MCI spent more time in the kitchen and looking into the fridge and kitchen cabinets than CH participants. Moreover, these measures were negatively associated with memory and executive performances of participants and significantly contributed to the prediction of MCI. CONCLUSION: Simple, wireless, and sensor-based technology holds potential for the detection of MCI in older adults as they perform daily tasks. However, some limits are discussed and we offer recommendations to improve the usefulness of this innovative approach.

Early Detection of Mild Cognitive Impairment With In-Home Monitoring Sensor Technologies Using Functional Measures: A Systematic Review.

The aging of the world population is accompanied by a substantial increase in neurodegenerative disorders, such as dementia. Early detection of mild cognitive impairment (MCI), a clinical diagnostic that comes with an increased chance to develop dementias, could be an essential condition for promoting quality of life and independent living, as it would provide a critical window for the implementation of early pharmacological and nonpharmacological interventions. This systematic review aims to investigate the current state of knowledge on the effectiveness of smart home sensors technologies for the early detection of MCI through the monitoring of everyday life activities. This approach offers many advantages, including the continuous measurement of functional abilities in ecological environments. A systematic search of publications in MEDLINE, EMBASE, and CINAHL, before November 2017, was conducted. Seventeen studies were included in this review. Thirteen studies were based on real-life monitoring, with several sensors installed in participants' actual homes, and four studies included scenario-based assessments, in which participants had to complete various tasks in a research lab apartment. In real-life monitoring, the most used indicators of MCI were walking speed and activity/motion in the house. In scenario-based assessment, time of completion, quality of activity completion, number of errors, amount of assistance needed, and task-irrelevant behaviors during the performance of everyday activities predicted MCI in participants. Despite technological limitations and the novelty of the field, smart home technologies represent a promising potential for the early screening of MCI and could support clinicians in geriatric care.

The Effects of Multi-Component Exercise Training on Cognitive Functioning and Health-Related Quality of Life in Older Adults.

PURPOSE: Exercise has been shown to have various proximal and distal benefits among older adults such as improving physical fitness, cognitive functioning, and health-related quality of life (HR-QOL). Despite this evidence, limited research has investigated pathway change of these outcomes. The primary purpose of this study was to test if older adults who improved in physical fitness measures from engaging in multicomponent exercise training for 12 weeks predicted change in proximal (cognitive functioning) and distal (HR-QOL) outcomes, respectively. METHODS: Participants (n = 110) were healthy, older adults (M = 72, SD = 7.24) that comprised an exercise-intervention and control group. The intervention consisted of exercising in a supervised laboratory setting for 12 weeks. RESULTS: Structural equation modeling revealed group type to predict change in physical performance and the maximum walking test with comparable effect sizes. Physical performance in turn predicted improvement in processing speed (ß = 0.23, p = 0.013) executive functioning (ß = 0.26, p = 0.006), and HR-QOL (ß = 0.13, p = 0.031). However, only executive functioning was found to significantly predict HR-QOL (ß = 0.49, p < 0.001) over processing speed (p > 0.05). CONCLUSIONS: Between two fitness measures, the physical performance test demonstrated better predictive validity in proximal and distal health outcomes. In addition to physical fitness, older adults who engage in multi-component exercise sessions regularly can improve their executive functioning, which in turn enhances their HR-QOL.

Can people with Alzheimer's disease improve their day-to-day functioning with a tablet computer?

New technologies, such as tablet computers, present great potential to support the day-to-day living of persons with Alzheimer's disease (AD). However, whether people with AD can learn how to use a tablet properly in daily life remains to be demonstrated. A single case study was conducted with a 65-year-old woman with AD. A specific and structured intervention tailored to her needs was conceptualised for the use of a calendar application on a tablet computer according to the following learning stages: Acquisition, Application and Adaptation. In spite of her severe episodic memory deficit, she showed progressive learning of the tablet application during the intervention phase. Furthermore, data compiled over 12 months post-use show that she used the tablet successfully in her day-to-day life. She was even able to transfer her newly acquired ability to other available applications designed to monitor regular purchases, consult various recipes and play games. Tablet computers thereby offer a promising avenue for cognitive rehabilitation for persons with AD. This success was mainly achieved through a one-on-one individual programme tailored to this person. The limits and constraints of utilising tablet computers for persons with AD are discussed.

Categories, diversity, and relevance of memory strategies reported by community-dwelling seniors.

BACKGROUND: Memory strategies help seniors remember information that is essential for the performance of their daily activities and contribute to their independence in the context of declining memory skills. This study aimed to analyze the categories, the diversity, and relevance of memory strategies known by seniors, and to identify individual characteristics that correlated with these variables. METHODS: The sample consisted of 294 participants aged 60 and over who decided to take part in a cognitive vitality promotion program. An adapted version of the memory situation questionnaire (Troyer, 2001) was administered to identify the memory strategies that seniors would use in five daily life situations. A scoring grid, also adapted from the questionnaire's original version (Troyer, 2001), was used to quantify the relevance of the strategies that were reported by participants. RESULTS: All participants mentioned at least once that they would use a strategy from the physical category of memory strategies. Out of a possible range of 26 strategies, participants answered an average of 6.14 (SD = 1.7) different answers across the five situations. Based on expert consensus, 67.7% of the mentioned memory strategies were relevant. Diversity and relevance were significantly higher when trying to remember appointments, things to bring or phone numbers (p ≤ 0.05). The level of education, cognitive skills, and participation in leisure activities were related to diversity and relevance of reported strategies. CONCLUSIONS: Seniors know various and relevant memory strategies to perform daily activities. The advantages of integrating strategies that they already know in cognitive health promotion programs should be considered in further studies.

Orthostatic hypotension associated with executive dysfunction in mild cognitive impairment.

INTRODUCTION: Midlife hypertension is associated with dementia in longitudinal studies while chronic hypotension in the elderly is associated with dementia onset. Orthostatic hypotension could influence cognitive performance in the elderly. The objective of this study was to assess the relationship between orthostatic hypotension and cognitive functions. METHODS: Consecutive participants with complete neuropsychological evaluation from a Memory Clinic were included. Orthostatic hypotension (OH) was defined by a fall≥20/10mmHg systolic/diastolic pressure. Participants were classified into one of 3 groups: 1) subjective cognitive impairment (SCI), 2) mild cognitive impairment (MCI), and 3) dementia. Neuropsychological tests were analyzed for patients with and without OH. RESULTS: One hundred and twenty participants were included, of which 16 (13%) were classified as SCI, 42 (35%) as MCI, and 63 (52%) with dementia. Prevalence of OH was 0% for the SCI group, 26% (n=11) for the MCI group, and 38% (n=24) for the dementia group. Age, sex, education, and brief cognitive test scores (MMSE & MoCA) were not different between groups with or without OH. In the MCI group, OH was associated with lower cognitive performance in several executive functions tests: visual working memory (p<0.001), processing speed (p=0.006), Stroop flexibility (p=0.030) and Trail-Making Test part B (p=0.024). There was no difference in episodic memory performance. OH was associated with a diagnosis of hypertension and the use of antihypertensive medication. No differences were observed in vascular brain injury between groups with and without OH. CONCLUSIONS: This study found that orthostatic hypotension prevalence is correlated to severity of cognitive deficits in a Memory Clinic. In MCI, OH is associated with lower performance in executive functions. OH could represent an under-recognized correlate of cognitive performance.

A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer's Disease: Preliminary Results from a Neuroimaging Study.

BACKGROUND: Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disease (AD). Little is known about the implication of the brain's two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. OBJECTIVE: To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. METHODS: In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. RESULTS: Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 µmol/100 g/min; p = 0.01). Plasma acetoacetate concentration and the blood-to-brain acetoacetate influx rate constant were also increased by 2-3-fold (all p≤0.03). CMRglu was unchanged after Walking (28.0±0.1 µmol/100 g/min; p = 0.96). There was a tendency toward improvement in the Stroop-color naming test (-10% completion time, p = 0.06). Performance on the Trail Making A&B tests was also directly related to plasma acetoacetate and CMRacac (all p≤0.01). CONCLUSION: In mild AD, aerobic training improved brain energy metabolism by increasing ketone uptake and utilization while maintaining brain glucose uptake, and could potentially be associated with some cognitive improvement.

Depressive symptoms are independently associated with recurrent falls in community-dwelling older adults.

ABSTRACT Background: Falls and depression are two major public health problems that affect millions of older people each year. Several factors associated with falls are also related to depressive symptoms such as medical conditions, sleep quality, use of medications, cognitive functioning, and physical capacities. To date, studies that investigated the association between falls and depressive symptoms did not control for all these shared factors. The current study addresses this issue by examining the relationship between falls and depression symptoms after controlling for several confounders. Methods: Eighty-two community-dwelling older adults were enrolled in this study. The Geriatric Depression Scale (GDS-30) was used to evaluate the presence of depressive symptoms, and the following question was used to assess falls: "Did you fall in the last 12 months, and if so, how many times?" Results: Univariate analyses indicated that the number of falls was significantly correlated with gender (women), fractures, asthma, physical inactivity, presence of depressive symptoms, complaints about quality of sleep, use of antidepressant drugs, and low functional capacities. Multivariate analyses revealed that depressive symptoms were significantly and independently linked to recurrent falls after controlling for confounders. Conclusions: Results of the present study highlight the importance of assessing depressive symptoms during a fall risk assessment.

Benefits of physical exercise training on cognition and quality of life in frail older adults.

OBJECTIVES: Frailty is a state of vulnerability associated with increased risks of fall, hospitalization, cognitive deficits, and psychological distress. Studies with healthy senior suggest that physical exercise can help improve cognition and quality of life. Whether frail older adults can show such benefits remains to be documented. METHOD: A total of 83 participants aged 61-89 years were assigned to an exercise-training group (3 times a week for 12 weeks) or a control group (waiting list). Frailty was determined by a complete geriatric examination using specific criteria. Pre- and post-test measures assessed physical capacity, cognitive performance, and quality of life. RESULTS: Compared with controls, the intervention group showed significant improvement in physical capacity (functional capacities and physical endurance), cognitive performance (executive functions, processing speed, and working memory), and quality of life (global quality of life, leisure activities, physical capacity, social/family relationships, and physical health). Benefits were overall equivalent between frail and nonfrail participants. DISCUSSION: Physical exercise training leads to improved cognitive functioning and psychological well-being in frail older adults.

The multiple dimensions of frailty: physical capacity, cognition, and quality of life.

BACKGROUND: Frailty is a complex health state of increased vulnerability associated with adverse outcomes such as disability, falls, hospitalization, and death. Along with physical impairments, cognition and quality of life may be affected in frail older adults. Yet, evidence is still lacking. The aim of this study was to compare frail and non-frail older adults on physical, cognitive, and psychological dimensions. METHODS: Thirty-nine frail and 44 non-frail elders were compared on several measures of physical capacity, cognition, and quality of life. Frailty status was based on a geriatric examination and scored using the Modified Physical Performance Test. RESULTS: After controlling for demographic and medical characteristics, physical capacity measures (i.e. functional capacities, physical endurance, gait speed, and mobility) were significantly lower in frail participants. Frail participants showed reduced performances in specific cognitive measures of executive functions and processing speed. On the quality of life dimension, frail elders reported poor self-perceptions of physical capacity, cognition, affectivity, housekeeping efficacy, and physical health. CONCLUSION: In addition to the reduced physical capacity, frailty might affect selective components of cognition and quality of life. These dimensions should be investigated in intervention programs designed for frail older adults.