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The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity.
Levakov, G, Kaplan, A, Yaskolka Meir, A, Rinott, E, Tsaban, G, Zelicha, H, Blüher, M, Ceglarek, U, Stumvoll, M, Shelef, I, et al
eLife. 2023;12
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Obesity is linked to premature brain ageing and subsequent development of diseases such as dementia and Alzheimer’s disease. Weight loss through lifestyle modifications may be able to attenuate brain ageing. This sub-study of 102 individuals from a randomised control trial known as the Dietary Intervention Randomised Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), aimed to determine the effect of 18 months lifestyle modifications and weight loss on brain age. The results showed that a decrease in BMI attenuated brain ageing and that 1% body weight loss reduced brain ageing by 8.9 months. Reduced brain age was also associated with decreased waist circumference and fat mass. Interestingly, reduced consumption of processed foods was also associated with reduced brain age. It was concluded that weight loss can be of benefit to brain health. This study could be used by healthcare professionals to understand that people with obesity are at a higher risk of brain related diseases, and that weight loss may be an effective way to prevent their development.
Abstract
BACKGROUND Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention. METHODS In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age. RESULTS To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months' attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age. CONCLUSIONS Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging. FUNDING The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai). Obesity is linked with the brain aging faster than would normally be expected. Researchers are able to capture this process by calculating a person’s ‘brain age’ – how old their brain appears on detailed scans, regardless of chronological age. This approach also helps to monitor how certain factors, such as lifestyle, can influence brain aging over relatively short time scales. It is not clear whether lifestyle interventions that promote weight loss can help to slow obesity-driven brain aging. To answer this question, Levakov et al. studied 102 individuals who met the criteria for obesity and took part in a lifestyle intervention aimed to improve diet and physical activity levels over 18 months. The participants received a brain scan at the beginning and the end of the program; additional tests and measurements were also conducted at these times to capture other biological processes impacted by obesity, such as liver health. Levakov et al. used the brain scans taken at the start and end of the study to examine the impact of the lifestyle intervention on the aging trajectory. The results revealed that a reduction in body weight of 1% led to the participants’ brain age being nearly 9 months younger than the expected brain age after 18 months. This attenuated aging was associated with changes in other biological measures, such as decreased liver fat and liver enzymes. Increases in liver fat and production of specific liver enzymes were previously shown to negatively impact brain health in Alzheimer’s disease. Finally, examining more closely the food consumption reports completed by participants showed that reduced consumption of processed food, sweets and beverages were linked to attenuated brain aging. The findings show that lifestyle interventions which promote weight loss can have a beneficial impact on the aging trajectory of the brain observed with obesity. The next steps will include determining whether slowing down obesity-driven brain aging results in better clinical outcomes for patients. In addition, the work by Levakov et al. demonstrates a potential strategy to evaluate the success of lifestyle changes on brain health. With global rates of obesity rising, identifying interventions that have a positive impact on brain health could have important clinical, educational and social impacts.
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Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
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Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
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Insufficient sleep predicts poor weight loss maintenance after 1 year.
Bogh, AF, Jensen, SBK, Juhl, CR, Janus, C, Sandsdal, RM, Lundgren, JR, Noer, MH, Vu, NQ, Fiorenza, M, Stallknecht, BM, et al
Sleep. 2023;46(5)
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Short sleep duration, defined as less than 6 hours/night, is associated with all-cause mortality, cardiovascular diseases, hypertension, diabetes, and obesity. Sleep restriction causes metabolic and behavioural changes suggesting that short sleep duration may contribute to the development of obesity. The aim of this study was to investigate associations between short sleep duration or poor sleep quality and weight regain after weight loss. This study is based on data from the S-LiTE randomised, controlled trial. Participants followed a low-calorie diet (800 kcal/day) for eight weeks prior to randomisation. Those who lost at least 5% of initial weight were randomised to the control or intervention group. Results showed that participants with objectively measured short sleep duration after a diet-induced weight loss had less success during weight loss maintenance than those with longer sleep duration. Worse sleep quality was associated with less weight loss during a low-calorie diet and subsequent weight maintenance. Authors conclude that insufficient sleep predicts weight regain during interventional efforts to maintain weight loss. Exercise maintained low-calorie diet-induced improvements in sleep quality during 1 year of weight loss maintenance, and liraglutide transiently increased sleep duration.
Abstract
STUDY OBJECTIVES Insufficient sleep may attenuate weight loss, but the role of sleep in weight loss maintenance is unknown. Since weight regain after weight loss remains a major obstacle in obesity treatment, we investigated whether insufficient sleep predicts weight regain during weight loss maintenance. METHODS In a randomized, controlled, two-by-two factorial study, 195 adults with obesity completed an 8-week low-calorie diet and were randomly assigned to 1-year weight loss maintenance with or without exercise and liraglutide 3.0 mg/day or placebo. Sleep duration and quality were measured before and after the low-calorie diet and during weight maintenance using wrist-worn accelerometers (GENEActiv) and Pittsburgh Sleep Quality Index (PSQI). To test associations between insufficient sleep and weight regain, participants were stratified at randomization into subgroups according to sleep duration (≥6 h/night) or sleep quality (PSQI score ≤/>5). RESULTS After a diet-induced 13.1 kg weight loss, participants with short sleep duration at randomization regained 5.3 kg body weight (p = .0008) and had less reduction in body fat percentage compared with participants with normal sleep duration (p = .007) during the 1-year weight maintenance phase. Participants with poor sleep quality before the weight loss regained 3.5 kg body weight compared with good quality sleepers (p = .010). During the weight maintenance phase, participants undergoing liraglutide treatment displayed increased sleep duration compared with placebo after 26 weeks (5 vs. -15 min/night) but not after 1 year. Participants undergoing exercise treatment preserved the sleep quality improvements attained from the initial weight loss. CONCLUSIONS Short sleep duration or poor sleep quality was associated with weight regain after weight loss in adults with obesity.
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Effects of Two Physical Activity Interventions on Sleep and Sedentary Time in Pregnant Women.
Alomairah, SA, Knudsen, SP, Roland, CB, Molsted, S, Clausen, TD, Bendix, JM, Løkkegaard, E, Jensen, AK, Larsen, JE, Jennum, P, et al
International journal of environmental research and public health. 2023;20(7)
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Pregnant women benefit from physical activity (PA) during pregnancy. The aim of this study was to assess the effect of the FitMum PA interventions on sleep quantity and quality and sedentary time (SED). This study was a secondary analysis of the FitMum study which included 220 healthy pregnant women. Participants were randomised to one of three groups. Results showed that pregnant women are prone to low sleep quality and high SED, which worsens as pregnancy progresses. Pregnant women who received structured supervised exercise training had better sleep quality and less SED than pregnant women receiving standard prenatal care when self-reported. Furthermore, when measured by a consumer activity tracker, no differences were observed between groups. Authors conclude that interventions that increase PA levels might improve sleep quality and decrease SED in pregnant women. Future behavioural interventions targeting pregnant women should include evidence-based content to improve sleep quality and reduce SED.
Abstract
Pregnancy is often associated with poor sleep and high sedentary time (SED). We investigated the effect of physical activity (PA) interventions on sleep and SED in pregnant women. A secondary analysis of a randomized controlled trial (n = 219) explored the effect of structured supervised exercise training (EXE) or motivational counseling on PA (MOT) compared to standard prenatal care (CON) on sleep and SED during pregnancy. Three times during pregnancy, sleep was determined by the Pittsburgh Sleep Quality Index (PSQI) and SED by the Pregnancy Physical Activity Questionnaire (PPAQ). Also, a wrist-worn consumer activity tracker measured sleep and SED continuously. Data from the activity tracker confirmed that sleep time decreases, and SED increases by approx. 30 and 24 min/day, respectively, from baseline (maximum gestational age (GA) week 15) to delivery. Compared to CON, the global PSQI score was better for EXE in GA week 28 (-0.8 [-1.5; -0.1], p = 0.031) and for both EXE and MOT in GA week 34 (-1 [-2; -0.5], p = 0.002; -1 [-2; -0.1], p = 0.026). In GA week 28, SED (h/day) from PPAQ was lower in EXE compared to both CON and MOT (-0.69 [-1; -0.0], p = 0.049; -0.6 [-1.0; -0.02], p = 0.042). In conclusion, PA interventions during pregnancy improved sleep quality and reduced SED.
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Effects of a 2-year exercise training on neuromuscular system health in older individuals with low muscle function.
Monti, E, Tagliaferri, S, Zampieri, S, Sarto, F, Sirago, G, Franchi, MV, Ticinesi, A, Longobucco, Y, Adorni, E, Lauretani, F, et al
Journal of cachexia, sarcopenia and muscle. 2023;14(2):794-804
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Ageing is accompanied by a progressive decline in muscle mass and functionality, associated with an increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality, possibly leading to a clinical syndrome known as sarcopenia. Among the causes of sarcopenia, motoneuron and neuromuscular junction (NMJ) degeneration have been proposed as key determinants. The aim of this study was to investigate the effects of a 2-year multimodal training intervention involving aerobic, strength and balance exercises on muscle mass and function, motoneuronal and NMJ health in a population of older individuals classified as sarcopenic. This study was a randomised controlled trial which enrolled 45 sarcopenic participants (34 females and 11 males) who were randomly assigned to one of the two groups: intervention or control group. Results show that the 2-year multimodal training intervention seemingly preserved NMJ stability, preventing serum C-terminal agrin fragment (CAF) [a biomarker of muscle wasting and weakness] concentration rise in the intervention group, although this biomarker increased significantly only in the control group. Conversely, neurofilament light chain (NfL) [clinical biomarker of many neurodegenerative diseases] concentration did not change in either group. Finally, improvements of physical performance were correlated with changes of serum biomarkers of NMJ stability. Authors conclude that a 2-year multimodal training intervention including aerobic, strength and balance exercises is effective for preventing CAF concentration increments, suggesting a positive effect on NMJ stability.
Abstract
BACKGROUND Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. METHODS Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. RESULTS At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. CONCLUSIONS The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.
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Neck-specific strengthening exercise compared with placebo sham ultrasound in patients with migraine: a randomized controlled trial.
Benatto, MT, Florencio, LL, Bragatto, MM, Dach, F, Fernández-de-Las-Peñas, C, Bevilaqua-Grossi, D
BMC neurology. 2022;22(1):126
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Patients with migraine may experience neck pain, worsened performance of cervical muscles, reduced cervical spine range of motion, and increased muscle sensitivity in the craniocervical region. Physiotherapy is an important nonpharmacological treatment option for reducing the duration and frequency of migraine attacks and may include manual therapy, soft-tissue techniques, and strength and endurance training. The aim of this study was to verify the effectiveness of craniocervical muscle-strengthening exercise (CMSE) in reducing the frequency and intensity of headache in migraine patients. This study is a two-armed, parallel-group randomized controlled trial. Men and women aged between 18 and 55 years, diagnosed only with migraine and at least three days of pain per month were included. Participants were randomly assigned to one of the two groups; intervention (n=21) or placebo (n=21) group. Results show that CMSE neither reduced the frequency and intensity of headache nor improved the performance and sensitivity of the cervical muscles, cervical range of motion, and migraine and neck pain-related disabilities. However, a significant improvement for pressure pain threshold was noticed in the sensitivity of the frontal muscle in favour of the intervention group. Authors conclude that performing CMSE is not enough to reduce the frequency and intensity of headache or improve the performance of the cervical muscles and reduce migraine and neck pain related disabilities.
Abstract
BACKGROUND Migraine patients have musculoskeletal disorders and pain in the cervical. And, despite the pathophysiology demonstrating the relationship between migraine and the cervical spine, the effectiveness of craniocervical exercises in these patients has not been verified. So, the aimed of this study was verify the effectiveness of craniocervical muscle-strengthening exercise (CMSE) in reducing the frequency and intensity of headache in migraine patients. METHODS A two-armed, parallel-group randomized controlled trial with a 3-month follow-up was performed. For eight weeks, the volunteers in the intervention group (n = 21) performed a protocol of CMSE, while those in the sham ultrasound group (n = 21) received the application of disconnected therapeutic ultrasound in the upper trapezius and guideline for home-stretching. The primary outcomes were the frequency and intensity of the headache. The secondary outcomes were questionnaires about migraine and neck disability, and satisfaction with the treatment, cervical range of motion, the pressure pain threshold, craniocervical flexion test (CCFT), cervical muscle strength and endurance test, and the cervical muscle activity during the physical tests. RESULTS No differences were observed for the changes observed in primary outcomes after eight weeks and at the 3-months follow up (p > 0.05). For the secondary outcomes, craniocervical exercises improved the sensitivity of the frontal muscle (p = 0.040) and promoted a reduced amplitude of muscle activity of the anterior scalene and upper trapezius in the last stages of CCFT (p ≤ 0.010). There was also reduced muscle activity of the anterior scalene and splenius capitis in the endurance test (p ≤ 0.045), as evaluated by surface electromyography. CONCLUSION CMSE were insufficient in reducing the frequency and intensity of headache, improving the performance of the cervical muscles, or reducing migraine and neck pain-related disabilities. This was found despite a decreased electromyographic activity of the cervical muscles during the last stages of CCFT and increased median frequency during the endurance test. TRIAL REGISTRATION Accession code RBR-8gfv5j , registered 28/11/2016 in the Registro Brasileiro de Ensaios Clínicos (ReBEC).
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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
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Aerobic Exercise Alters Brain Function and Structure in Parkinson's Disease: A Randomized Controlled Trial.
Johansson, ME, Cameron, IGM, Van der Kolk, NM, de Vries, NM, Klimars, E, Toni, I, Bloem, BR, Helmich, RC
Annals of neurology. 2022;91(2):203-216
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An increasing number of studies suggest that motor symptoms associated with Parkinson’s disease (PD) can be improved through physical exercise. The aim of this study was to investigate the effect of aerobic exercise on cerebral changes (PD symptoms, brain function, and eye movements). This study is a single-centre, prospective double-blind, randomised, placebo-controlled trial. Participants (n=56) were randomly assigned to one of two intervention groups (1:1 ratio) - two home-based exercise programs: aerobic exercise (n=25) or stretching (n=31). Results show that aerobic exercise stabilises motor progression and enhances cognitive performance in individuals with PD by stimulating functional and structural plasticity in corticostriatal sensorimotor and cognitive control networks. Authors conclude aerobic exercise stimulates functional and structural neuroplasticity in both motor and cognitive brain networks in PD.
Abstract
OBJECTIVE Randomized clinical trials have shown that aerobic exercise attenuates motor symptom progression in Parkinson's disease, but the underlying neural mechanisms are unclear. Here, we investigated how aerobic exercise influences disease-related functional and structural changes in the corticostriatal sensorimotor network, which is involved in the emergence of motor deficits in Parkinson's disease. Additionally, we explored effects of aerobic exercise on tissue integrity of the substantia nigra, and on behavioral and cerebral indices of cognitive control. METHODS The Park-in-Shape trial is a single-center, double-blind randomized controlled trial in 130 Parkinson's disease patients who were randomly assigned (1:1 ratio) to aerobic exercise (stationary home trainer) or stretching (active control) interventions (duration = 6 months). An unselected subset from this trial (exercise, n = 25; stretching, n = 31) underwent resting-state functional and structural magnetic resonance imaging (MRI), and an oculomotor cognitive control task (pro- and antisaccades), at baseline and at 6-month follow-up. RESULTS Aerobic exercise, but not stretching, led to increased functional connectivity of the anterior putamen with the sensorimotor cortex relative to the posterior putamen. Behaviorally, aerobic exercise also improved cognitive control. Furthermore, aerobic exercise increased functional connectivity in the right frontoparietal network, proportionally to fitness improvements, and it reduced global brain atrophy. INTERPRETATION MRI, clinical, and behavioral results converge toward the conclusion that aerobic exercise stabilizes disease progression in the corticostriatal sensorimotor network and enhances cognitive performance. ANN NEUROL 2022;91:203-216.
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The consequences of exercise-induced weight loss on food reinforcement. A randomized controlled trial.
Flack, KD, Hays, HM, Moreland, J
PloS one. 2020;15(6):e0234692
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Exercise is a long-standing remedy for nearly all of obesity’s comorbidities and often recommended as an economical and health-promoting option for weight loss and weight loss maintenance. The aim of this study was to investigate the effect of exercise on food reinforcement (reward-driven feeding), and to examine whether changes in body composition would be correlated with changes in food reinforcement. This study is randomized controlled trial with a total of 52 participants aged 18 to 40 years. Participants were randomly assigned to one of the three groups (six exercise sessions per week, two sessions per week, and sedentary control). Results indicate that there is great variability in individuals’ change in food reinforcement after a 12-week aerobic exercise intervention. Furthermore, those who did increase their food reinforcement were also those who lost the greatest amount of fat-free mass post-intervention. Authors conclude that preventing the loss of fat-free mass may be a valuable piece to a weight loss programme (with resistance training or dietary protein intake as adjunct therapy).
Abstract
BACKGROUND Obesity remains a primary threat to the health of most Americans, with over 66% considered overweight or obese with a body mass index (BMI) of 25 kg/m2 or greater. A common treatment option many believe to be effective, and therefore turn to, is exercise. However, the amount of weight loss from exercise training is often disappointingly less than expected with greater amounts of exercise not always promoting greater weight loss. Increases in energy intake have been prescribed as the primary reason for this lack of weight loss success with exercise. Research has mostly focused on alterations in hormonal mediators of appetite (e.g.: ghrelin, peptide YY, GLP-1, pancreatic polypeptide, and leptin) that may increase hunger and/or reduce satiety to promote greater energy intake with exercise training. A less understood mechanism that may be working to increase energy intake with exercise is reward-driven feeding, a strong predictor of energy intake and weight status but rarely analyzed in the context of exercise. DESIGN Sedentary men and women (BMI: 25-35 kg/m2, N = 52) were randomized into parallel aerobic exercise training groups partaking in either two or six exercise sessions/week, or sedentary control for 12 weeks. METHODS The reinforcing value of food was measured by an operant responding progressive ratio schedule task (the behavioral choice task) to determine how much work participants were willing to perform for access to a healthy food option relative to a less healthy food option before and after the exercise intervention. Body composition and resting energy expenditure were assessed via DXA and indirect calorimetry, respectively, at baseline and post testing. RESULTS Changes in fat-free mass predicted the change in total amount of operant responding for food (healthy and unhealthy). There were no correlations between changes in the reinforcing value of one type of food (healthy vs unhealthy) to changes in body composition. CONCLUSION In support of previous work, reductions in fat-free mass resulting from an aerobic exercise intervention aimed at weight loss plays an important role in energy balance regulation by increasing operant responding for food.
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The effects of yoga and quiet rest on subjective levels of anxiety and physiological correlates: a 2-way crossover randomized trial.
Albracht-Schulte, K, Robert-McComb, J
BMC complementary and alternative medicine. 2018;18(1):280
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Increased stress and anxiety levels can lead to elevated cardiovascular responses and reduced capacity for stress recovery. Recent studies have found both an acute period of rest and bout of acute aerobic exercise to be effective in reducing stress, suggesting time away from stressors is what alters anxiety levels. Yoga has been reported to improve both physiological and psychological coping response to stressors, however yoga has not been studied in this context. The aim of this randomised, crossover study was to determine the effects of 30 minutes of yoga and seated rest on anxiety measures, namely heart rate variability (HRV), in forty healthy female university students. Participants were randomised to either begin with seated rest or vinyasa yoga, and after each session were shown 90 emotionally stimulating photos. Post-exposure stress and anxiety responses were measured. This study found both rest and yoga were effective for acutely reducing anxiety levels, however these positive effects did not persist after exposure to emotional stimuli. Based on these results, the authors support the theory that time away from stressors is important for reducing anxiety.
Abstract
BACKGROUND Rest or acute exercise can decrease state anxiety, with some evidence showing exercise to prevent laboratory-induced elevations in anxiety. No study has examined whether yoga provides short-term protection against laboratory-induced anxiety. The aim of this study was to examine the effectiveness of an acute YogaFit session on state anxiety and measures of heart rate variability (HRV) to determine whether yoga provides short-term protection against emotional picture stimuli. METHODS A randomized repeated-measures crossover clinical trial was performed. Forty healthy, female college students completed a 30 min session of YogaFit and a time-matched seated rest condition on separate days. After each condition, participants viewed 30 min of emotional picture stimuli. State anxiety, heart rate and time-domain and frequency-domain measures of HRV were assessed baseline, post- condition, and post-exposure to emotional stimuli. Data were analysed using a condition x time (2 × 3) repeated-measures ANOVA. RESULTS Post-hoc comparisons indicate the following: (1) state anxiety significantly decreased from baseline to post-condition for both yoga and rest (p = 0.001) but returned to baseline values following exposure to emotional stimuli (p < 0.001) for both conditions; (2) heart rate decreased post-condition to post-exposure (p = 0.020) and baseline to post-exposure (p = 0.033) for both conditions; (3) time-domain measure of HRV showed a significant increase in HRV between baseline and post-condition (p = 0 .019), post-condition and post-exposure (p = 0 .007), and between baseline and post-exposure (p < 0.001). CONCLUSIONS Both YogaFit and seated rest were effective at acutely reducing state anxiety post-condition, but not at preventing an induced anxiety response post-exposure. Following exposure to the emotionally stimulating pictures, there was a shift from the high frequency-domain to the low frequency-domain and an increase in the time-domain measure of HRV for both the YogaFit and the quiet rest condition. TRIAL REGISTRATION Retrospectively registered 2/16/2018, clinicaltrials.gov, Identifier: NCT03458702 .