Cognitive Plasticity in Healthy Older Adults: Effects of Nonpharmacological Interventions and Predictors of Intervention Success

Background: Even in the absence of health problems, the ageing process is associated with deficits in cognitive functioning. One way to maintain cognitive abilities in healthy older adults is the participation in cognitive training (CT) interventions or combined cognitive and physical training (CPT) interventions. However, so far it is unclear, which of these non-pharmacological interventions is the most efficient. Furthermore, one question that also has not been properly investigated is: Who benefits most from these non-pharmacological interventions? So far, data is rare and inconsistent regarding which specific characteristics of individuals predict success of CT and CPT. Yet, this knowledge is highly relevant as it would facilitate the design of new, optimally tailored programs for subgroups to ensure individual-centered prevention of cognitive decline in the age of personalized medicine. Aims: The overall aims of this thesis were (i) to investigate whether CT and CPT can help healthy older individuals to maintain or even improve their cognitive functions and (ii) to identify possible factors that determine who benefits most from CT and/or CPT directly after an intervention and at follow-up one year later. Methods: The thesis comprises four studies. Study I was a partly randomized controlled trial comparing the effectiveness of a structured CT (n = 35 healthy older individuals) with an unstructured CT (n = 35) and a passive control group (n = 35) directly after the intervention. This study identifies predictors of CT success. Study II investigates the effectiveness of a CT (n = 23 healthy older individuals) compared to a CPT (n = 28) and a CPT plus counselling (n = 30) one year after the intervention. Furthermore, possible predictors for CPT success one year after the intervention were investigated. Study III focuses on predictors of short- and long-term CT success. Analyses of Study II and Study III were based on the same data. Study IV is a systematic review of studies (n = 28) investigating predictors of memory training success in healthy older individuals. Results: The main results of Study I showed that attending a structured CT was more effective than attending an unstructured CT and no intervention (the control group) to improve verbal short-term memory. Results of Study II showed a significant effect favouring the CPT in comparison to CPT plus counselling in the domains overall cognition and verbal long-term memory. Also, within-group comparisons showed cognitive improvements for all types of training. Regarding predictors of CT and CPT success in healthy older individuals, results of Studies I, II and III show that “more vulnerable” groups (i.e., individuals with less education, at an older age, and with worse performance on neuropsychological tests at training entry) can benefit more from CT as well as from CPT both directly after the training and one year later. The systematic review conducted in Study IV revealed that the statistical analyses and dependent variables used to calculate predictors of memory training success differ greatly and may explain the partly conflicting results regarding predictors of training success in the existing literature. Conclusion: The present thesis contributes to the research into the effectiveness of CT and CPT interventions by showing that both CT and CPT interventions are suitable for maintaining and improving cognitive functions in healthy older adults. Furthermore, substantial contributions were made to the investigation of possible predictors of CT and CPT success, thus taking an important step toward an individualized prevention approach to maintaining cognitive abilities in healthy older ageing. Moreover, the identification of methodological shortcomings in prediction research so far will contribute to the establishment of guidelines and a higher methodological quality of future prediction research

Nothing wrong about change: the adequate choice of the dependent variable and design in prediction of cognitive training success

Background Even though investigating predictors of intervention success (e.g Cognitive Training, CT) is gaining more and more interest in the light of an individualized medicine, results on specific predictors of intervention success in the overall field are mixed and inconsistent due to different and sometimes inappropriate statistical methods used. Therefore, the present paper gives a guidance on the appropriate use of multiple regression analyses to identify predictors of CT and similar non-pharmacological interventions. Methods We simulated data based on a predefined true model and ran a series of different analyses to evaluate their performance in retrieving the true model coefficients. The true model consisted of a 2 (between: experimental vs. control group) x 2 (within: pre- vs. post-treatment) design with two continuous predictors, one of which predicted the success in the intervention group and the other did not. In analyzing the data, we considered four commonly used dependent variables (post-test score, absolute change score, relative change score, residual score), five regression models, eight sample sizes, and four levels of reliability. Results Our results indicated that a regression model including the investigated predictor, Group (experimental vs. control), pre-test score, and the interaction between the investigated predictor and the Group as predictors, and the absolute change score as the dependent variable seemed most convenient for the given experimental design. Although the pre-test score should be included as a predictor in the regression model for reasons of statistical power, its coefficient should not be interpreted because even if there is no true relationship, a negative and statistically significant regression coefficient commonly emerges. Conclusion Employing simulation methods, theoretical reasoning, and mathematical derivations, we were able to derive recommendations regarding the analysis of data in one of the most prevalent experimental designs in research on CT and external predictors of CT success. These insights can contribute to the application of considered data analyses in future studies and facilitate cumulative knowledge gain

Lower cognitive baseline scores predict cognitive training success after 6 months in healthy older adults: Results of an online RCT

Background: Identifying predictors for general cognitive training (GCT) success in healthy older adults has many potential uses, including aiding intervention and improving individual dementia risk prediction, which are of high importance in health care. However, the factors that predict training improvements and the temporal course of predictors (eg, do the same prognostic factors predict training success after a short training period, such as 6 weeks, as well as after a longer training period, such as 6 months?) are largely unknown. Methods: Data (N = 4,184 healthy older individuals) from two arms (GCT vs. control) of a three-arm randomized controlled trial were reanalyzed to investigate predictors of GCT success in five cognitive tasks (grammatical reasoning, spatial working memory, digit vigilance, paired association learning, and verbal learning) at three time points (after 6 weeks, 3 months, and 6 months of training). Possible investigated predictors were sociodemographic variables, depressive symptoms, number of training sessions, cognitive baseline values, and all interaction terms (group*predictor). Results: Being female was predictive for improvement in grammatical reasoning at 6 weeks in the GCT group, and lower cognitive baseline scores were predictive for improvement in spatial working memory and verbal learning at 6 months. Conclusion: Our data indicate that predictors seem to change over time; remarkably, lower baseline performance at study entry is only a significant predictor at 6 months training. Possible reasons for these results are discussed in relation to the compensation hypothesis. J Am Geriatr Soc 68:-, 2020.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Alzheimer's Society UKpublished version, accepted version (12 month embargo), submitted versio

Parallel and serial task processing in the PRP paradigm: a drift–diffusion model approach

Even after a long time of research on dual-tasking, the question whether the two tasks are always processed serially (response selection bottleneck models, RSB) or also in parallel (capacity-sharing models) is still going on. The first models postulate that the central processing stages of two tasks cannot overlap, producing a central processing bottleneck in Task 2. The second class of models posits that cognitive resources are shared between the central processing stages of two tasks, allowing for parallel processing. In a series of three experiments, we aimed at inducing parallel vs. serial processing by manipulating the relative frequency of short vs. long SOAs (Experiments 1 and 2) and including no-go trials in Task 2 (Experiment 3). Beyond the conventional response time (RT) analyses, we employed drift–diffusion model analyses to differentiate between parallel and serial processing. Even though our findings were rather consistent across the three experiments, they neither support unambiguously the assumptions derived from the RSB model nor those derived from capacity-sharing models. SOA frequency might lead to an adaptation to frequent time patterns. Overall, our diffusion model results and mean RTs seem to be better explained by participant’s time expectancies

A systematic review and meta-analysis of social cognition training success across the healthy lifespan

Socio-cognitive abilities and challenges change across the healthy lifespan and are essential for successful human interaction. Identifying effective socio-cognitive training approaches for healthy individuals may prevent development of mental or physical disease and reduced quality of life. A systematic search was conducted in MEDLINE Ovid, Web of Science Core Collection, CENTRAL, and PsycInfo databases. Studies that investigated different socio-cognitive trainings for healthy individuals across the human lifespan assessing effects on theory of mind, emotion recognition, perspective taking, and social decision making were included. A random-effects pairwise meta-analysis was conducted. Risk-of-Bias was assessed using the Cochrane Risk-of-Bias-2-Tool. Twenty-three intervention studies with N = 1835 participants were included in the systematic review; twelve randomized controlled trials in the meta-analysis (N = 875). Socio-cognitive trainings differed regarding duration and content in different age groups, with theory of mind being the domain most frequently trained. Results of the meta-analysis showed that trainings were highly effective for improving theory of mind in children aged 3–5 years (SMD = 2.51 (95%CI: 0.48–4.53)), children aged 7–9 years (SMD = 2.71 (95%CI: − 0.28 to 5.71)), and older adults (SMD = 5.90 (95%CI: 2.77–9.02). Theory of mind training was highly effective in all investigated age-groups for improving theory of mind, yet, more research on transfer effects to other socio-cognitive processes and further investigation of training effects in other socio-cognitive domains (e.g., emotion recognition, visual perspective taking, social decision making) is needed. Identified characteristics of successful socio-cognitive trainings in different age groups may help designing future training studies for other populations

Progression of socio-cognitive impairment from healthy aging to Alzheimer’s dementia: A systematic review and meta-analysis

Background: Trajectories of decline across different socio-cognitive domains in healthy older adults and in pathological aging conditions have not been investigated. This was addressed in the present systematic review and meta-analysis. Methods: MEDLINE, Web of Science Core Collection, CENTRAL, and PsycInfo were searched for studies investigating social cognition across four domains (Theory of Mind, ToM; emotion recognition, ER; Social-decision making, SD; visual perspective taking, VPT) in healthy older individuals, individuals with subjective and mild cognitive impairment (SCD, MCI) and Alzheimer’s disease (AD). Random-effects meta-analyses were conducted. Results: Of 8137 screened studies, 132 studies were included in the review. ToM and ER showed a clear progression of impairment from normal aging to AD. Differential patterns of decline were identified for different types of ToM and ER. Conclusion: This systematic review identified progression of impairment of specific socio-cognitive abilities, which is the necessary pre-requisite for developing targeted interventions. We identified a lack of research on socio-cognitive decline in different populations (e.g., middle age, SCD and MCI-subtypes) and domains (SDM, VPT)

Task-based profiles of language impairment and their relationship to cognitive dysfunction in Parkinson’s disease

Objective: Parkinson's Disease (PD) is associated with both motor and non-motor problems, such as cognitive impairment. Particular focus in this area has been on the relationship between language impairment and decline in other cognitive functions, with the literature currently inconclusive on how the nature and degree of language impairment relate to cognition or other measures of disease severity. In addition, little information is available on how language problems identified in experimental task set-ups relate to competency in self-generated language paradigms such as picture description, monologues or conversations. This study aimed to inform clinical management of language impairment in PD by exploring (1) language performance across a range of experimental as well as self-generated language tasks, (2) how the relationship between these two aspects might be affected by the nature of the cognitive and language assessment; and (3) to what degree performance can be predicted across the language tasks. Methods: 22 non-demented people with PD (PwPD) and 22 healthy control participants performed a range of cognitive and language tasks. Cognitive tasks included a screening assessment in addition to tests for set shifting, short term memory, attention, as well as letter and category fluency. Language was investigated in highly controlled grammar tasks as well as a Sentence Generation and a Narrative. Results: The study highlighted impaired ability in set-shifting and letter fluency in the executive function tasks, and a higher rate of grammatical and lexical errors across all language tasks in the PD group. The performance in the grammar task was linked to set shifting ability, but error rates in Sentence Generation and Narrative were independent of this. There was no relevant relationship between performances across the three language tasks. Conclusions: Our results suggest that there is a link between executive function and language performance, but that this is task dependent in non-demented PwPD. This has implications for the management of language impairment in PD, both for assessment and for designing effective interventions

Effects of a Cognitive Training With and Without Additional Physical Activity in Healthy Older Adults: A Follow-Up 1 Year After a Randomized Controlled Trial

Background: Combining cognitive training (CT) with physical activity (CPT) has been suggested to be most effective in maintaining cognition in healthy older adults, but data are scarce and inconsistent regarding long-term effects (follow-up; FU) and predictors of success.Objective: To investigate the 1-year FU effects of CPT versus CT and CPT plus counseling (CPT+C), and to identify predictors for CPT success at FU.Setting and Participants: We included 55 healthy older participants in the data analyses; 18 participants (CPT group) were used for the predictor analysis.Interventions: In a randomized controlled trial, participants conducted a CT, CPT, or CPT+C for 7 weeks.Outcome Measures: Overall cognition, verbal, figural, and working memory, verbal fluency, attention, planning, and visuo-construction.Results: While within-group comparisons showed cognitive improvements for all types of training, only one significant interaction Group × Time favoring CPT in comparison to CPT+C was found for overall cognition and verbal long-term memory. The most consistent predictor for CPT success (in verbal short-term memory, verbal fluency, attention) was an initial low baseline performance. Lower education predicted working memory gains. Higher levels of insulin-like growth factor 1 (IGF-1) and lower levels of brain-derived neurotrophic factor at baseline (BDNF) predicted alternating letter verbal fluency gains.Discussion: Within-group comparisons indicate that all used training types are helpful to maintain cognition. The fact that cognitive and sociodemographic data as well as nerve growth factors predict long-term benefits of CPT contributes to the understanding of the mechanisms underlying training success and may ultimately help to adapt training to individual profiles.Clinical Trial Registration: WHO ICTRP (http://apps.who.int/trialsearch/), identifier DRKS00005194