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Protocols for cognitive enhancement. A user manual for Brain Health Services—part 5 of 6
Alzheimer's Research & Therapy volume 13, Article number: 172 (2021)
Abstract
Cognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.
We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.
CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.
We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs (“smart drugs”, acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.
Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.
Background
Forgetfulness is one of the most common worries among the elderly. While in some cases, subjects are satisfied with their cognitive functions and simply concerned about preserving them (worried-well, WW), others perceive a subjective decline in cognition in the absence of objective evidence of cognitive impairment (subjective cognitive decline, SCD). Although not described in DSM-V or ICD-11, the detection of SCD in clinical practice and the knowledge that biomarkers of neurodegenerative disorders appear long before the onset of objective cognitive deficits was a motivation for the SCD-Initiative working group to establish research criteria [1], recently commented and completed by Jessen et al. (2020) [2].
Representing a high percentage of patients seeking help in memory clinics for whom specific instructions are lacking [3], the definition of interventions to reduce the risk of cognitive decline and dementia in these subjects is a clinical need that is unmet. Up to 40 % of dementia cases could in fact be prevented by acting on modifiable factors (e.g., cardiovascular factors, depression, physical inactivity, social isolation, education) [4], thus interventions should target cognitively unimpaired individuals [5], especially those who have SCD. In order to address this need, we envision the creation of Brain Health Services, i.e. new services with specific missions, namely dementia risk profiling [6], dementia risk communication [7], dementia risk reduction [8], and cognitive enhancement [9], and with specific societal challenges [10].
This review focuses on randomized control trials (RCT) assessing techniques expected to improve cognition, thus targeting interventions that generally improve the performance in a short-term period (weeks, months), including cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, and nutrients.
The goal is to make “actionable” clinical recommendations based, whenever possible, on the Grading of recommendations assessment, development, and evaluation (GRADE) methodology.
Cognitive, mental, or physical training (CMPT)
Here we considered as a CMPT intervention any training that had a potential impact on cognition, including cognitive intervention, physical activity and mental training e.g., mindfulness meditation.
Two recent papers, a systematic review and a meta-analysis, addressed the topic of cognitive enhancement with various interventions on the SCD population [11, 12]. Both of them found encouraging results in favor of a positive effect, not only on cognition, but also on well-being and quality of life. Smart et al. (2017) reviewed 9 studies (mainly RCT) addressing the effect of various non-pharmacological interventions on SCD older than 55 years [11]. Despite a large heterogeneity of designs and study quality, the interventions had a positive impact on the outcomes, with a small global effect size (effect size = 0.22, highest density intervals (HDI) = 0.01 to 0.51), which increased when taking into consideration only cognitive interventions (including mindfulness meditation) (effect size = 0.37, HDI: 0.06 to 0.71). Bhome et al. (2018) included 20 studies with both non-pharmacologic and pharmacologic interventions [12]. Cognitive training improved slightly, but significantly, objective cognitive performance. In contrast, psychological interventions (e.g., psycho-education, mindfulness meditation) significantly improved well-being but failed to improve metacognitive abilities or other cognitive performances.
Cognitive interventions and physical training
Cognitive intervention is a powerful mean to stimulate brain plasticity, as it showed not only an impact on behavior but also on the brain [13,14,15]. There are two main kinds of cognitive interventions: restorative (repeated practice) and compensation programs (strategic learning) (see Table 2); they both imply to train a specific cognitive function. However, a restorative program targets a dysfunctional cognitive function and aims to improve it with repeated practice. A compensatory program aims at supporting the impaired function, relying on unimpaired functions, and using strategies or metacognitive skills to compensate via alternative pathways [16].
Physical training intervention is a structured and repetitive program of physical exercise among which aerobic is usually an important part. It can be associated with some cognitive training or not. Studies showed that exercise leads to an increase in brain tissue, notably in the hippocampus, and an increased level of brain-derived neurotrophic factor [17].
Mindfulness meditation
Meditation refers to a set of emotional and attentional regulatory training exercises [18, 19], encompassing different practices, such as focused attention, open monitoring, and loving-kindness meditations [19]. Several mindfulness-based therapy programs have been developed for health care, the first one being the mindfulness-Based Stress Reduction program by Dr. Jon Kabat-Zinn [20]. Meditation-based intervention programs usually combine weekly sessions with an instructor and daily home practice, sometimes associated with one day of more intense practice. A typical meditation practice session would consist in sitting down in quiet environment and bringing your attention on your breath, without effort, gently refocusing on your breath each time your mind wanders, without judgment. Each session can combine different types of meditative practice, which relate to different targets, such as increasing skills in regulation of attention, skills in meta-cognition, and skills in compassion and loving-kindness [19, 21]. Most of the studies currently rely on 8-weeks mindfulness-based intervention, while longer interventions have recently been developed [21, 22].
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