Effects of multidomain lifestyle interventions on cognitive decline and Alzheimer's disease prevention: A literature review and future recommendations.

Alzheimer's disease (AD) is a neurodegenerative disorder with an increasing incidence and currently without a cure. It is speculated that targeting multiple modifiable risk factors (MRFs) could be a beneficial strategy for the prevention of cognitive decline and AD. This study provides an overview and discusses the existing literature on multidomain lifestyle interventions in relation to cognitive decline and the prevention of AD. A literature search was performed in PubMed and Scopus, for studies published in English up to 31 May 2021. We identified nine relevant studies on the effect of multidomain lifestyle interventions on cognition (n = 8) and/or AD incidence or risk scores (n = 4). The studies included a combination of the separate intervention components diet (n = 8), physical activity (n = 9), cognitive activity (n = 6), metabolic or cardiovascular risk factor reduction strategies (n = 8), social activity (n = 2), medication (n = 2), and/or supplementation (n = 1). Global cognition was improved significantly in four of the eight studies that had global cognition as the outcome. Moreover, significant improvements were shown for cognitive domains in two of the three studies with specific cognitive domains as an outcome. No effect on AD incidence was observed, although positive results were shown for AD risk scores. The results suggest that multidomain lifestyle intervention studies may be partially effective in preventing cognitive decline. However, studies were heterogeneous and limited in follow-up. Future research on the effect of multidomain lifestyle interventions on cognitive decline and AD incidence must be conducted with a longer follow-up period.

Effect of an exercise intervention on global cognition after transient ischemic attack or minor stroke: the MoveIT randomized controlled trial.

BACKGROUND: Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition. METHODS: The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years. RESULTS: The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, - 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1). CONCLUSIONS: No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients. TRIAL REGISTRATION: http://www.trialregister.nl . Unique identifier: NL3721 . Date first registration: 06-03-2013.

Young people and adolescents have more irregular meals during the COVID-19 pandemic: A nested case-control study on chrono-nutrition before and during the COVID-19 pandemic.

Chrono-nutrition is an emerging field of research that includes three aspects of time: (1) regularity, (2) frequency, and (3) clock time. Due to the COVID-19 pandemic and the implemented lockdown, daily routines were disrupted, which presented a unique opportunity to investigate chrono-nutrition, in particular in adolescents. A nested case-control study was conducted and information on chrono-nutrition was collected via an anonymous online questionnaire including 99 participants aged 13 to 20 years (N = 43 before the COVID-19 pandemic and N = 56 during the COVID-19 pandemic). Differences in chrono-nutrition were tested with chi-square and Mann-Whitney U. During the COVID-19 pandemic, participants consumed their breakfast less regularly (34%) compared with participants before the COVID-19 pandemic (65%) (P = .003). Additionally, during the COVID-19 pandemic, participants consumed snacks in the morning (26% vs. 60%, P = .001), afternoon (19% vs. 81%, P < .000), and evening (22% vs. 84%, P < .001) less regularly. However, the frequency in afternoon (4.9 ± 2.2 times per week vs. 3.8 ± 1.9 times per week, P = .002) and evening snacks (4.4 ± 2.4 times per week vs. 3.4 ± 2.0 times per week, P = .02) was higher for participants during the COVID-19 pandemic. We also observed that participants reported more sleeping problems during the COVID-19 pandemic (34% vs. 14%; P = .07). This study in 99 young people and adolescents suggests that meal regularity declined during the COVID-19 pandemic, while meal frequency, especially snack consumption, increased. This highlights the importance of maintaining a regular daily structure to avoid excessive energy intake via snacks.

TIMELAPSE study-efficacy of low-dose amitriptyline versus cognitive behavioral therapy for chronic insomnia in patients with medical comorbidity: study protocol of a randomized controlled multicenter non-inferiority trial.

BACKGROUND: Insomnia is common in people with long-term medical conditions and is related to increased mortality and morbidity. Cognitive behavioral therapy for insomnia (CBT-I) is first choice treatment and effective for people with insomnia and comorbid long-term medical conditions. However, CBT-I has some limitations as it might not always be available or appeal to patients with medical conditions. Furthermore, a small proportion of patients do not respond to CBT-I. Preliminary evidence and clinical experience suggest that low-dose amitriptyline (AM) might be an effective alternative to treat insomnia in patients with medical comorbidity. In this randomized controlled trial, we will determine whether AM is non-inferior to the first choice treatment for insomnia, CBT-I. METHODS/DESIGN: This study will test if treatment with low-dose amitriptyline for insomnia in patients with medical comorbidity is non-inferior to CBT-I in a multicenter randomized controlled non-inferiority trial. Participants will be 190 adults with a long-term medical condition and insomnia. Participants will be randomly allocated to one of two intervention arms: 12 weeks AM (starting with 10 mg per day, and if ineffective at 3 weeks, doubling this dose) or 12 weeks of CBT-I consisting of 6 weekly sessions and a follow-up session 6 weeks later. The primary outcome is subjective insomnia severity, measured with the Insomnia Severity Index (ISI). The primary endpoint is at 12 weeks. Secondary outcomes include sleep quality (e.g., sleep efficiency), questionnaires on daytime functioning (physical functioning and impairment of functioning), and symptoms (e.g., fatigue, pain, anxiety) at 12 weeks and 12 months post treatment and relapse of insomnia until 12 months after treatment. DISCUSSION: Irrespective of the outcome, this study will be a much-needed contribution to evidence based clinical guidelines on the treatment of insomnia in patients with medical comorbidity. TRIAL REGISTRATION: Dutch Trial Register NTR NL7971 . Registered on 18 August 2019.

Physical Activity and Characteristics of the Carotid Artery Wall in High-Risk Patients-The SMART (Second Manifestations of Arterial Disease) Study.

BACKGROUND: Physical activity reduces the risk of vascular disease. This benefit is not entirely explained through an effect on vascular risk factors. We examined the relationship of physical activity and characteristics of the carotid artery wall in patients with vascular disease or risk factors. METHODS AND RESULTS: Cross-sectional analyses were performed in 9578 patients from the SMART (Second Manifestations of Arterial Disease) study, a prospective cohort study among patients with vascular disease or risk factors. Physical activity was assessed using questionnaires. Carotid intima-media thickness and carotid artery stenosis of both common carotid arteries was measured. In a subset of 3165 participants carotid diastolic diameter and distension were assessed. Carotid stiffness was expressed as the distensibility coefficient and Young's elastic modulus. Regression analyses adjusted for vascular risk factors showed that physical activity was inversely associated with diastolic diameter (fifth versus first quintile B=-0.13 mm; 95% CI, -0.21 to -0.05) and decreased risk of carotid artery stenosis (relative risk, 0.58; 95% CI, 0.48-0.69). A light level of physical activity was associated with less carotid stiffness (second versus first quintile; Young's elastic modulus B=-0.11 kPa-1×10-3; 95% CI, -0.16 to -0.06; distensibility coefficient B=0.93 kPa×103; 95% CI, 0.34-1.51), but there was no additional benefit with increasing levels of physical activity. In patients with vascular disease, physical activity was inversely associated with common carotid intima-media thickness, but not in patients with vascular risk factors. CONCLUSIONS: In patients with vascular disease or risk factors, increased physical activity was associated with smaller carotid diastolic diameter, decreased risk of carotid artery stenosis, and less carotid stiffness, but it only showed benefits on carotid intima-media thickness in patients with vascular disease.

Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

Cardiorespiratory Fitness after Transient Ischemic Attack and Minor Ischemic Stroke: Baseline Data of the MoveIT Study.

BACKGROUND: Cardiorespiratory fitness (CRF) is reduced in patients with stroke. It is unclear whether it is also reduced in patients with a transient ischemic attack (TIA) or minor stroke. We investigated the CRF in patients with a recent TIA or minor stroke and explored which determinants are associated with a lower fitness. METHODS: In 113 patients with a recent TIA or minor ischemic stroke (64 (SD = 10) years of age; 49 (IQR 27-86) days post TIA or stroke), the peak oxygen consumption (VO2peak) was determined in a symptom-limited ramp exercise test. Physical activity level, vascular risk factors, history of vascular or pulmonary disease, and stroke characteristics were recorded at inclusion and related to the VO2peak. RESULTS: Mean VO2peak was 22 mL/kg/min (SD = 6), which is the fifth percentile of age- and sex-related normative values. Increasing age and female sex were associated with a lower VO2peak (B (95% CI): per 10 years -2.57 mL/kg/min (-3.75; -1.40) and female sex -5.84 mL/kg/min (-8.06; -3.62)). Age- and sex-adjusted linear regression analyses showed that a history of cardiovascular disease and pulmonary disease was associated with a lower VO2peak. In addition, a lower level of physical activity, hypertension, smoking, and overweight were associated with a lower VO2peak. History of stroke and stroke characteristics were not related to VO2peak. CONCLUSION: The majority of patients with a recent TIA or minor ischemic stroke have a poor CRF. Our findings suggest that premorbid cardiovascular and pulmonary disease and vascular risk factors, but not TIA- or stroke-related factors, contribute to a reduced CRF.

Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome.

We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy.

Physical Activity and Vascular Events and Mortality in Patients with Vascular Disease.

INTRODUCTION: In patients with CAD, moderate levels of leisure time physical activity are associated with lower risk of mortality. However, less is known about the effects in patients with vascular disease other than CAD. In this study, we examined the association between physical activity and risk of future vascular events and all-cause mortality in patients with vascular disease or risk factors and investigated whether these associations were similar across the different manifestations of vascular disease. METHODS: A total of 9942 consecutive patients with various manifestations of vascular disease or risk factors enroled in the Second Manifestations of ARTerial disease study were included. The amount of physical activity was assessed at baseline in MET-hours per week. RESULTS: The study population (mean age, 56.7 yr; male, 67%) had a median level of physical activity of 17.4 MET·h·wk(-1). During a median follow-up of 6.7 yr, 1224 vascular events and 1353 cases of all-cause mortality were recorded. Cox regression analyses adjusted for age, sex, smoking, and current alcohol consumption showed that higher levels of physical activity were associated with reduced risk of vascular events (quartile 4 vs quartile 1; hazard ratio, 0.68 (95% confidence interval, 0.58-0.79)) and all-cause mortality (hazard ratio, 0.61 (95% confidence interval, 0.53-0.71)). This reduced risk was observed both in patients with vascular disease and in patients with risk factors. The associations were similar across the different manifestations of vascular disease. CONCLUSIONS: Higher levels of leisure time physical activity were associated with reduced risk of vascular events and all-cause mortality in patients with CAD and other manifestations of vascular disease, suggesting that physical exercise programs should also be investigated in these other manifestations.