Lifestyle and Brain Health PDF

Estils de vida i salut cerebral Tema 6: Intervenció sobre estils de vida Dr. Kilian Abellaneda Pérez [email protected] Unitat de Psicologia Mèdica, Departament de Medicina Facultat de Medicina i Ciències de la Salut Universitat de Barcelona Estructura de la clase 1. 2. 3. 4. Introducció...

Estils de vida i salut cerebral Tema 6: Intervenció sobre estils de vida Dr. Kilian Abellaneda Pérez [email protected] Unitat de Psicologia Mèdica, Departament de Medicina Facultat de Medicina i Ciències de la Salut Universitat de Barcelona Estructura de la clase 1. 2. 3. 4. Introducció Aspectes bàsics en recerca biomèdica Intervencions en salut cerebral Intervencions en salut mental 2 Introduction Hippocrates of Kos (460 – 370 BC) is considered one of the most outstanding figures in the history of medicine. He is often referred to as the "Father of Medicine". • Importància EDVs • Personalització EDVs Què et crida l’atenció d’aquesta frase? A què es refereix Hipòcrates? 3 Introduction: Lifestyle components We are still identifying and defining all the components of a healthy lifestyle Which are they? There is a consensus? 4 Types of study in biomedical research Quins tipus d’estudis en recerca biomèdica coneixes? Què és, el teu article dels seminaris? Altres classificacions: Quins tipus d’estudis hem vist, sobretot, en aquesta assignatura? Causality? Recerca primària vs. Recerca secundària ... 5 “Engage Your Brain: GCBH Recommendations on Cognitively Stimulating Activities.” Available at: www.GlobalCouncilOnBrainHealth.org Observational vs. RCTs. The example of meditation 6 Observational vs. RCTs. The example of meditation 7 Biomedical research: experimental variables Quines son les variables que necessitem en un estudi controlat? The two main variables in an experiment are the independent and dependent variable. • An independent variable is the variable that is changed or controlled in a scientific experiment to test the effects on the dependent variable. à Ex: Dosi d’un fàrmac. • A dependent variable is the variable being tested and measured in a scientific experiment. à Ex: Simptomatologia clínica. Carlson, Robert. A concrete introduction to real analysis. CRC Press, 2006. p.183. Dodge, Y. (2003) The Oxford Dictionary of Statistical Terms, OUP. Everitt, B. S. (2002). The Cambridge Dictionary of Statistics (2nd ed.). Cambridge UP. 8 Quan parlem d’estudis en neurociència... El cervell i la conducta ... son VI o VD? WM neural paterns in young adults Both brain and behavior can be dependent or independent variables depending on the design: Focal perinatal parietal lesion Language skills assessed at age 6 - Evaluation of the effects of brain lesions in a specific region (independent variable) on a given behavior (dependent) - Evaluation of the effects of a memory task (independent variable) on brain activation (dependent variable) Depèn del disseny! 9 Biomedical research: experimental control Què és el control experimental? • In an experiment, data from an experimental group is compared with data from a control group. • The only difference between the two groups is that the independent variable is changed in the experimental group. • Experiments involving human subjects can be much more complex. Algun exemple fora de la biomedicina...? Bailey, R. A. (2008). Design of Comparative Experiments. Cambridge University Press. Chaplin, S. (2006). "The placebo response: an important part of treatment". Prescriber: 16–22. Hinkelmann, Klaus; Kempthorne, Oscar (2008). Design and Analysis of Experiments, Volume I: Introduction to Experimental Design (2nd ed.). Wiley. 10 Introduction: Experimental control - Placebo • In humans, if we're testing whether a drug is effective or not, for example, members of a control group may expect they will not be unaffected. • In this case, a placebo may be used. • A placebo is a substance or similar that doesn't contain an active therapeutic agent. • If a control group takes a placebo, participants don't know whether they are being treated or not, so they have the SAME EXPECTATIONS as members of the experimental group. The active control (AC) intervention was developed to control for nonspecific effects inherent to supervised CCT. Participants viewed seven short National Geographic videos per session on a computer and answered multiple-choice questions immediately after each presentation. 11 The training intervention included practicing the mnemonic technique MoL The active control group program involved popular scientific lectures once a week. Young and old adults De Lange et al. 2017. Human Brain Mapping El placebo sempre es controla amb una “sugar pill” o amb un grup control més o menys “actiu”? 13 Quina és una de les principals limitacions dels estudis RCT? 14 An issue in lifestyle interventions: Adherence • Lifesyle interventions report disappointing outcomes and reduced effectiveness due to poor adherence rates. • Adherence has been defined as "the extent to which a person's behaviour corresponds with agreed recommendations from a healthcare provider”. • A better understanding of the determinants of adherence is key for successful programmes. WHY? • Expectatives a curt termini poc realistes? • Manca d’interès intrínsec en el canvi? 15 An issue in lifestyle interventions: Adherence • Motivation, also described as willpower or determination, is reportedly high in the initial stages of a lifestyle intervention programme; however, maintaining that motivation is challenging. • Barriers to behavior change need to be addressed early in the intervention. • If adherence were improved, treatment effectiveness, health outcomes and the ultimate burden of chronic disease could be improved. Pràctica de l’assignatura: Ex: Apps esportives 16 Lifestyle interventions for distinct conditions Salut cerebral: Envelliment i demències Salut mental: Depressió i ansietat 17 Per quin motiu els estils de vida son tant rellevants en l’envelliment i la demència? AGING AND DEMENTIA • Increased life expectancy represents one of the biggest transformations of age structure among contemporary societies (United Nations, 2017; 2020). • Age is a principal risk factor for many highly prevalent and disabling disorders, including Alzheimer’s disease (AD). • Disease-modifying agents to counteract cognitive impairment in older age remain elusive. • Identifying modifiable factors promoting reserve and resilience is paramount (Arenaza-Urquijo et al., 2015; Cattaneo et al., 2018). United Nations, Population Division, 2017 Aging and dementia Advanced age encompasses most disabilityadjusted life-years (DALYs) due to neurological conditions, such as: - cerebrovascular disorders - neurodegenerative disorders GBD 2015 Neurological Disorders Collaborator Group, 2017 19 Aging and dementia INTER-INDIVIDUAL VARIABILITY IN COGNITION COGNITIVE CHANGES IN AGING Nyberg et al., 2012. Cereb. Cortex. Park and Reuter-Lorenz, 2009. Annu. Rev. Psychol. Yaffe et al., 2009. Neurology. 20 Aging and dementia 2. Ho podem traslladar aquí? 1. Què podem aprendre d’aquí? 21 Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease Observational studies have identified several potentially modifiable risk factors for dementia, including: 1) diabetes mellitus 2) midlife hypertension 3) midlife obesity 4) physical inactivity 5) depression 6) smoking 7) low education Randomized clinical trials are needed to investigate whether interventions targeting these risk factors can reduce the risk of cognitive decline and dementia in elderly adults. Kivipelto et al. 2018. Nat Rev Neurol 22 • Late-life cognitive impairment, dementia and AD are multifactorial and heterogeneous disorders that are driven by a constellation of genetic and environmental risk and protective factors, including vascular, lifestyle-related and psychosocial factors. • Many of these risk factors and protective factors are potentially modifiable and thus offer opportunities for prevention. • In fact, consistent evidence from observational studies estimates that one-third of AD cases worldwide are attributable to seven common modifiable risk factors (physical inactivity, low education…). Interaccions gent x ambient importants! Ex: APOE & TBI Kivipelto et al. 2018. Nat Rev Neurol 23 ¿Hi ha alguna relació entre els TCEs i la demència? Hi ha algun element genètic compartit en relació als outcomes? Chronic traumatic encephalopathy The best known genetic risk factor for poor outcome after traumatic brain injury (TBI) in adults is the E4 allele of the apolipoprotein E (APOE) gene. Si la demència s’explica per múltiples factors, quin tipus d’intervencions caldria fer? Unimodals, o multimodals? 27 Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease • In contrast to the positive results from observational studies that examined the capacity for diet, physical activities and cognitive activities to prevent cognitive impairment or dementia, evidence from RCTs has been limited. • Many interventions are either conducted in small groups of participants, have a short duration or both, especially in the case of physical activity. Kivipelto et al. 2018. Nat Rev Neurol 28 Intervencions unimodals • Dieta • Exercici • Activitat cognitiva 29 Inclusion criteria - only trials with the following attributes: 1. 2. 3. 4. Randomized allocation to intervention and control conditions Cognitive assessment done both before and after the intervention Study duration of at least 1 year A sample size of at least 500 participants 30 Single-domain lifestyle interventions: Diet Vs. The OPAL study investigated the effect of daily omega-3 supplement compared with olive oil supplement over 2 years Found no difference between the groups (no decline in control nor active) WHY…? Is olive oil a “neutral” control? – Too much active? A 2-yr intervention is too short? 31 Single-domain lifestyle interventions: Exercise LIFE STUDY: DESIGN AND METHODS • Objective To determine whether a 24-month physical activity program results in better cognitive function. • Interventions A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. • Participants: Sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. 32 Single-domain lifestyle interventions: Exercise LIFE STUDY: RESULTS • Intervention reduced incident major mobility disability. • No significant differences between groups in any cognitive outcomes. • Intervention had a beneficial effect among those aged ≥80 years and among those with a low level of physical activity at baseline. SHOULD WE PRESCRIBE EXERCISE PREFERENTLY TO SPECIFIC POPULATIONS? 33 Single-domain lifestyle interventions: Cognitive training Participants: healthy older adults who underwent three 1-h weekly sessions of either multidomain CCT program (n = 7) or an active control intervention (n = 5) over 12 weeks . PILOT DATA 34 Single-domain lifestyle interventions: Cognitive training ACTIVE STUDY: DESIGN AND METHODS • Objective To evaluate whether 3 cognitive training interventions improve 1) mental abilities and 2) daily functioning in older adults aged 65 to 94 years. • Interventions Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory, reasoning, or speed of processing or a no-contact control group. 35 Single-domain lifestyle interventions: Cognitive training ACTIVE STUDY: RESULTS • Each intervention improved targeted cognitive ability compared with baseline durable to 2 to 10 years. • Cognitive training did not affect rates of incident dementia. • No training effects on everyday functioning were detected. I LA VALIDESA ECOLÒGICA…? 36 Single-domain lifestyle interventions: Cognitive training IHAMS STUDY Computerized visual speed of processing training: a) 10 hours on-site b) 10 hours + 4-hour booster on-site c) 10 hours at home d) attention training (control) All intervention groups had small to medium improvements in the primary outcome: the Useful Field of View (UFOV) test, a measure cognitive processing speed. Converted to years of protection against age-related cognitive decline, these effects reflect 3.0 to 4.1 years on UFOV. 37 MAKE ANY SENSE TRAINING SPEED OF PROCESSING? ENS CALEN MODELS SÒLIDS PER FER INTERVENCIONS (i.e., LLENG / MEM PROC?) 38 Single-domain lifestyle interventions: Cognitive training nonverbal memory • CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains: + memory, working memory, processing speed, and visuospatial skills - executive functions and attention. • Weak evidence for sessions less than 30 min • Unsupervised at-home training was not effective. verbal memory Quins inputs tenim fins aquí? • • • • Efectes modestos a nivell d’exercici i cognitiu, no dieta. Efectes cognitius dependents del domini. Efectes notables en subjectes específics (i.e., exercici). La interacció de factors (i.e.,socialització) pot ser rellevant? Què necessitem per fer-ho millor...? 40 Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease • Given the multifactorial aetiology of dementia, multidomain interventions that target several risk factors and mechanisms simultaneously might be necessary for an optimal preventive effect. • In the past few years, three large multidomain trials have been completed: 1) FINGER (Finland) 2) MAPT (France) 3) PreDIVA (The Netherlands) Multidomain lifestyle interventions: (1) FINGER • The first large multidomain RCT, the FINGER tested the efficacy of a multidomain lifestyle intervention to prevent cognitive decline. • FINGER enrolled 1260 elderly adults (60-77) who were at risk of cognitive decline (CAIDE>6) from the general population • The study tested the efficacy of a 2-year multidomain intervention comprising: 1) nutritional guidance (i.e., 25–35 g/day of dietary fibre, less than 5 g/day of salt) 2) Exercise (i.e., dose responses to exercise training protocol) 3) cognitive training (i.e., group and individual sessions) 4) social activity (stimulated through the numerous group meetings) 5) intensive monitoring and management of metabolic and vascular risk factors The control group received general health advice. Ngandu et al., 2015. Lancet 43 The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score enables the prediction of the later risk of dementia on the basis of the risk factor profile present in midlife (age 40–65 years). 44 Hi ha alguna cosa sorprenent en el grup placebo? Practice effects of repeated cognitive testing might partly account for improvements in both groups. Improvement was significantly greater in the intervention group suggesting cognitive benefits beyond practice Multidomain lifestyle interventions: (1) FINGER • The study showed a beneficial effect of the intervention on the primary outcome, which was the change in cognition as measured by a comprehensive neuropsychological test battery (NTB) score. • Significant intervention effects for the secondary cognitive outcomes of executive functioning (p=0·039) and processing speed (p=0·029. • The intervention was not associated with significant change in the memory domain. • This intervention might be generalizable to most of the elderly population who have risk of dementia. Ngandu et al., 2015. Lancet 45 Multidomain lifestyle interventions:(2) MAPT • The study enrolled 1680 people aged 70 years or older frail individuals. • Four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. • The main result on the primary outcome was negative (composite cognitive measure). • Post hoc analyses that pooled together both groups receiving the multidomain intervention showed beneficial cognitive effects. • Furthermore, the multidomain+omega-3 intervention was effective among frail individuals with risk of dementia. Fragilitat (Fried et al. 2001): Si en avaluar un pacient gran podeu identificar tres dels cinc indicadors següents com a presents, podeu caracteritzar el pacient com a fràgil: pèrdua de pes involuntària; sensació d’esgotament; debilitat; velocitat de marxa lenta i baixos nivells d'activitat física. Vellas et al., (2014). J. Prev. Alzheimers. Dis. 46 Multidomain lifestyle interventions:(3) Pre-DIVA The PreDIVA trial tested the efficacy of a 6-year, nurse-led, multidomain cardiovascular intervention compared with control intervention (usual care) for the prevention of dementia. TENS ALGUN ESTUDI EN MENT, OBSERVACIONAL, SOBRE AQUEST ASPECTE? Millor rendiment en memòria verbal i en velocitat psicomotora als 43-55 anys s’associa amb millors aptituds cardiorespiratòries 25 anys abans 47 Multidomain lifestyle interventions:(3) Pre-DIVA • The PreDIVA recruited 3526 participants aged 70–78 years. • The intervention consisted of visits to a practice nurse every 4 months, for a period of 6 years (18 visits). During these visits, the nurse assessed these risk factors: smoking habits, diet, physical activity, weight, and blood pressure. • The intervention did not result in an overall decrease of dementia incidence. • The intervention had a protective effect for non-Alzheimer dementia. • In addition, a reduced occurrence of dementia was found in a subgroup of people with baseline untreated hypertension. QUINS TIPUS DE DEMÈNCIA NO-ALZHEIMER CONEIXES? Moll van Charante et al., 2016. Lancet 48 Fazekas scale Fluid attenuated inversion recovery – FAZEKAS SCALE https://epos.myesr.org/poster/esr/ecr2018/C-0076 Mahammedi A, Wang LL, Williamson BJ, et al. Small Vessel Disease, a Marker of Brain Health: What the Radiologist Needs to Know. AJNR Am J Neuroradiol. 2022;43(5):650660. doi:10.3174/ajnr.A7302 53 Inputs from multimodal interventions? • • • The FINGER trial showed that a multidomain lifestyle intervention can benefit cognition in elderly people with an elevated risk of dementia. Additional analyses from MAPT and Pre-DIVA among participants at risk of dementia or cardiovascular risk showed more beneficial effects from the intervention. Results from these three trials suggest that targeting of preventive interventions to at-risk individuals might be an effective strategy. PERSONALIZED MULTIDOMAIN LIFESTYLE RECCOMENDATIONS!! 54 Mental health: Lifestyle interventions 55 Lifesytle interventions in anxiety disorders: • Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. • Adverse events in the escitalopram group were insomnia or sleep disturbance (41%), nausea (35%), fatigue (26%), headache (18%), somnolence (14%), among others. Lifesytle interventions in depression non-severe depression 57 Lifesytle interventions in depression 58 Lifestyle interventions in aging and mental health Lifestyle interventions in mental health Mental health professionals have significantly underestimated the importance of lifestyle factors (a) as contributors to and treatments for multiple psychopathologies. (b) for boosting individual and social well-being. (c) for preserving and optimizing cognitive function. Walsh, 2011. American Psychologist 60 Lifestyle interventions in mental health ADVANTAGES/DISADVANTAGES OF THERAPEUTIC LIFESTYLE CHANGES? • TLCs can be as effective as psychotherapy or medication for treating some mental health conditions • TLCs can be used alone or adjunctively and are often accessible and affordable; many can be introduced quickly, sometimes even in the first session. • Unlike both psychotherapy and pharmacotherapy, they are free of stigma and can even confer social benefits. • They have fewer side effects and complications than medications. • Many TLCs not only reduce psychopathology symptoms in patients but can also enhance psychological well-being in normal populations. THE BAD? • Parameters selections (dose estimation) • Need for personalization Walsh, 2011. American Psychologist 61 During the COVID-19 pandemic (N=682), we document large disruptions to physical activity, sleep, screen time use, and mental health. At the onset of the pandemic, average steps decline from 10,000 to 4,600 steps per day, sleep increases by 25 to 30 min per night, time spent socializing declines by over half to less than 30 min, and screen time more than doubles to over 5 h per day. Over the course of the pandemic the proportion of participants at risk for clinical depression ranges from 46% to 61%, up to a 90% increase in depression rates compared to the same population prior to the pandemic. 62 In June 2020 we implemented a randomized intervention to further stimulate physical activity among our participants. We randomly assigned participants to receive incentives for walking a minimum of 10,000 steps a day. WHY IS THIS? 1. First, the impact of physical activity may require a more intensive intervention. 2. Second, physical activity may have important interactions with other lifestyle behaviors such as social interactions. 3. Another possibility is that the relationship between physical activity and well-being is driven primarily by mental health rather than lifestyle. 63