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. 2021 Oct 11;13(1):172.
doi: 10.1186/s13195-021-00844-1.

Protocols for cognitive enhancement. A user manual for Brain Health Services-part 5 of 6

Andrea Brioschi Guevara #  1 , Melanie Bieler #  2 , Daniele Altomare  3   4 , Marcelo Berthier  5   6 , Chantal Csajka  7   8   9 , Sophie Dautricourt  10 , Jean-François Démonet  2 , Alessandra Dodich  11 , Giovanni B Frisoni  3   4 , Carlo Miniussi  11 , José Luis Molinuevo  12 , Federica Ribaldi  3   4   13   14 , Philip Scheltens  15 , Gael Chételat  10
Affiliations

Protocols for cognitive enhancement. A user manual for Brain Health Services-part 5 of 6

Andrea Brioschi Guevara et al. Alzheimers Res Ther. .

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.

Keywords: Brain Health Service; Cognitive enhancement; Cognitive intervention; Drugs; Mindfulness meditation; Non-invasive brain stimulation; Physical training; Subjective cognitive decline.

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Conflict of interest statement

JLM is currently a full-time employee of Lundbeck and has previously served as a consultant or an advisory boards for the following for-profit companies, or has given lectures in symposia sponsored by the following for-profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, ProMIS Neurosciences.

PS has received consultancy fees (paid to the institution) from AC Immune, Alkermes, Alnylam, Anavex, Biogen, Brainstorm Cell, Cortexyme, Denali, EIP, ImmunoBrain Checkpoint, GemVax, Genentech, Green Valley, Novartis, Novo Noridisk, PeopleBio, Renew LLC, Roche. He is PI of studies with AC Immune, CogRx, FUJI-film/Toyama, IONIS, UCB, Vivoryon. He serves on the board of the Brain Research Center.

JFD has received consultancy fees from Biogen and OM Pharma; unrestricted grants from OM Pharma; and has collaboration agreements with Siemens and MindMaze.

GBF reports grants from Alzheimer Forum Suisse, Académie Suisse des Sciences Médicales, Avid Radiopharmaceuticals, Biogen, GE International, Guerbert, Association Suisse pour la Recherche sur l’Alzheimer, IXICO, Merz Pharma, Nestlé, Novartis, Piramal, Roche, Siemens, Teva Pharmaceutical Industries, Vifor Pharma, and Alzheimer’s Association; he has received personal fees from AstraZeneca, Avid Radiopharmaceuticals, Elan Pharmaceuticals, GE International, Lundbeck, Pfizer, and TauRx Therapeutics.

The other co-authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
NIBS methods. a TMS. b tDCS. a TMS is able to generate a brief electric field in the targeted brain surface that causes a rapid depolarization of neurons above threshold. The repeated application of TMS (rTMS) induces effects that are defined as neuromodulation: low-frequency rTMS (< 1 Hz) mainly induces a reduction in the excitability, while high-frequency rTMS (between 5 and 25 Hz) induces facilitating effects in terms of excitability of the stimulated area (see [24]). b tDCS involves the application of weak electrical currents directly to the scalp, through a pair of electrodes, for a few minutes (~ 5–20). These currents generate an electric field that modulates neuronal activity. Several studies showed that anodal tDCS increases the frequency of neurons spontaneous discharge in the stimulated area, while cathodal tDCS has the opposite effect (see [25, 26])
Fig. 2
Fig. 2
a Dose of CMPT intervention for experimental groups. b Duration of CMPT intervention for experimental groups. Legend: a Minimum (dark green) and maximum (light green) experimental interventions’ dose for each elicited GRADE outcome. Squares indicate the mean dose and mustaches the standard deviation. b Idem for duration
See this image and copyright information in PMC

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