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Task 9. Take action (Effects of cognitive training = see if combined…

- - - - (1) heterogeneity of the intervention programs: Most intervention studies used memory performance as the primary outcome measure, but only few studies used similar tests to measure memory functioning which frustrated a more quantitative meta-analysis on these studies (methological problem= different tests used).
        
        Different intervention programs proved to be effective in improving either objective or subjective memory performance; training of memory strategies, attention, pyscho-educational lessions on memory and lifestyle, computarized training on memory performance and training on metacognition. EF included as a secondary measure.
      - (2) Methodological quality of the studies: differed vastly. Inclusion of active control: looking at the RCTs in the healthy older adults, ten RCTs included an active control condition. These studies did show an effect on measures of cognitive functioning, more specifically executive functioning, speed, attention, and subjective memory functioning.
        
        In MCI populations, when applying this control, not significant effect was found. Evaluating the results of intervention studies with an active control condition, it may be concluded that cognitive interventions can have a positive effect on various aspects of both objective and subjective cognitive functioning in healthy older adults, but not in people with MCI
      - (3) Little evidence for generalization effects to overall cognitive interventions and daily life interventions. (4) training evidence that it could be preserve for a couple of months, but did not show maintenance of effect after 1 years (5) it is still not clear the difference in effect between MCI and healthy older adults: does they benefit from different trainings?
      - Critics of the review: selective terms could have been biased, maybe had very small range of years, publication bias, only included english-papers, selection of the reviews: two persons- assistant & researcher, should find the same ones, if not, discuss it together or find a 3rd rater. only one of them selected papers based on criteria -author bias, review base-
- - - - Phase 1: **systematic review** (pubmed was searched), looked also for novel risk factors. Selected population-based sample, prospective design, with big samples an older than 45 years old participants, with 1 year of follow-up.
      - Phase 2: Delphi study-first round.The Delphi study was conducted among experts in dementia epidemiology and prevention. Online survey and each participant (8) named freely potential risk factors for all-type dementia in subjective order of important (rank score)
      - Phase 3: synthesis of information. Evidence was aggregated by compiling lists with the major modifiable risk factors from both literature review (n° of studies, consistency in direction of association, effect size) and the first Delphi round (risk factor´s total RS). The preliminary risk factor inventory included the highest-ranking factors from both methods.
      - Phase 4: Delphi study- second round. The same experts were provided with the results from systematic review and the aggregated results of the first Delphi round. They were invited to comment on the preliminary risk factor inventory. Experts weighted the risk factors in order of importance for primary prevention of dementia by a general practitioner
    - - Depression: Experts rated depression as the most important risk factor in the second Delphi round. Recent-meta analyses report a 90% higher risk for AD or 85% higher risk for all-type dementia
      - Diabetes: Experts ranked diabetes as the second most important risk factor in both Delphi rounds. Diabetes carried a 47% increased risk dementia. The pathological mechanisms linking diabetes to cognitive decline and dementia are not fully understood but might include metabolic, vascular, and inflammatory processes
      - Cognitive activity: all studies of cognitive activity found a decreased risk. Ranked 3rd by experts. Two large prospective studies suggest a 62% lower risk of AD in older adults who engage in cognitive stimulating leisure activities. Cognitive activity may delay cognitive decline by increasing an individual´s cognitive reserve
      - Physical activity:. Experts rated it 4th. Physical inactivity was found to increased dementia by 49%. The mechanisms of brain activity were shown to be direct or indirect, as a cardioprotective factors.
      - Hypertension: : midlife hypertension is associated with a 61% of increased risk of developing dementia. Possible mechanisms include atherosclerosis, white matter lesions, increased neuritic plaques and tangles, and atrophy
      - Diet:. mediterranean diet - a higher adherence was associated with less cognitive decline and a reduced risk of AD, but not MCI.
      - Other factors: colesterol (10th factor: 54% increase risk influences beta-amyloid metabolism and neurofibrillary tangle formation, , coronary heart disease, renal dysfunction, unsaturated fat intake, inflammation.
      - Risk factors are unlikely to occur in isolation, but might interact in a synergistic or antagonistic way, or form clusters (syndrommes). Crucial identification of midlife modifiable risk factors in order to intervene at an early stage of the disease process.
      - Smoking -associated with 59% risk. associated with inflammatory and vascular risks- (8) and alcohol -36%(9)- low-to-moderate consumption. Chronic abuse leads to a more serious disorder. The damage can be caused by neurotoxicity, nutritional deficiency, neuro-inflammation, and changes in NT systems.
  - - - Low education contributed to the largest proportion of AD cases worldwide. It is believed that education and mental stimulation throughout life may lower risk of dementia by helping to build a cognitive reserve, that enables individuals to keep functioning at a "normal " levels despite experiencing neurodegenerative changes. Biomarkers = less predictive of development of AD in those with high-cognitive reserve. => interventions to enhance educational opportunities throughout the lifecourse could potentially prevent millions of AD cases from becoming symptomatic.
      - Smoking: second-largest number of AD cases globally. The most likely mechanism underlying the association between smoking and AD is vascular disease. Smoking contributes to a variety of subclinical and clinical vascular disorders including atherosclerosis and cerebrovascular disease (increase risk of AD): Related also to neurotoxins and inflammatory processes.
      - physical inactivity: third-factor globally. Influences both directly and indirectly (physical inactivity is
        associated with increased risk of several cardiovascular risk factors—such as diabetes,
        hypertension and obesity)
      - Depression: forth largest contributor globally (pro-dromal or risk factor?- rf most likely). Vascular disease has been hypothesized as one of the potential mechanisms by which depression could increase risk of dementia and cognitive impairment -reciprocal relation- also associated with alterations in stress-related hormones, lower levels of neuronal growth factors and reduced hippocampal volume.
      - Mid-life obesity, mid-life hypertension and diabetes- peripheral hyperinsulemia
        could potentially inhibit brain insulin production, which could in turn result in impaired
        amyloid clearance in the brain.90
- - - - Participants from 60-77 years old, followed for two years in a double blind randomised study. Inclusion criteria was dementia risk and cognition at normal level. The multidomain intervention was the experimental group, in the control group only general health advise was given. Primary outcome: change in cognition (neuropsych testing).
      - Controlled for demographic variables, vascular factors, lifestyle factos and self-reported medical disorders.
    - - More improvement in intervention group. More detailed, executive function and processing speed (but not memory) increased significantly more in the intervention group
      - Instead of healing the disease, focus has shifted to pre-symptomatic and predementia disease stages and at-risk states when intervention might not be too late.A modest delay in onset would have a huge effect on individual and societal levels. I
      - FINGER was the first large longer-term and robust trial showing that a multidomain intervention can improve or maintain cognitive functioning and reduce the risk of cognitive decline among older at-risk individuals, and thus lowers the risk factors/form a protective factor for cognitive decline
      - Intensity of intervention, type of intervention (eg. multidomain), long duration and choice of target group (at-risk individuals) might account the observed beneficial effects on cognition.
- - - - PREDIMED: (prevención con dieta mediterránea) randomized clinical trial reported that, compared with a control diet consisting of advice to reduce dietary fat, a mediterrenean diet supplemented with extra virgin olive oil or mixed nuts for nearly 5 years reduced the incidence of cardiovascular diseases by 30% in older individuals at high risk. The diet had anti-inflamattory and antioxidant components.
      - Participants underwent neuropsychological test to assess cognition at 2-time points. Baseline and follow-up (study termination). Tests used: fluency test, digit span, working memory, and the color trail test, measure attention, visomotor speed, and cognitive flexibility. Participants were selected based on having diabetes or cardiovascular risk factors.
      - 3 intervention groups: (1) mediterranean diet supplemented with extra-virgin olive oil (2) mediterranean diet supplemented with mix nuts (3) control diet. Collected dietary data via inteerviews and taught them how to use it.
      - Results: cognitive functions
        
        Results revealed cognitive improvement in participants allocated in the Mediterranean diet and cognitive decline in those allocated in the control diet
        
        This benefit was independent of sex, age, energy intake, and cognition-related variables, including education level, APOE 4 genotype, and vascular risk.
        
        Difference in the diets (scientific evidence?)
        
        Participants in the Mediterranean diet plus olive oil group had improved frontal functional and global cognition composites (composite refer to clustering tests in each domain = calculate z scores of all memory tests.) Difference in each test and also frontal fucntion.
        
        The beneficial effect is probably related to the abundance of antioxidants and anti-inflammatory agents that they provide. May counteract oxidative processes in the brain, leading to neurodegeneration. Polyphenols can ameliorate neurologic health by additional mechanisms, including improved cerebrovascular blood low, modulation of neuronal signalling, enhanced synthesis of neurotrophic factors and stimulation of neurogenesis. Also, vascular improvement. Other risk factors of AD are diabetes and blood pressure, which the diet also helped with. Clearence of b-amylodi and increasing of brain protection mechanisms.
        
        Participants allocated to the Mediterranean diet plus nuts had improvement in the memory composite compared with those ascribed the control diet
        
        Decline in the control group
        
        can´t generalize to population = risk population (diabetes and cardiovascular diseases)