The Latest Articles on Cognitive Ageing

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Cognitive Ageing.

Title: Prediction of cognitive performance differences in older age from multimodal neuroimaging data
Authors: Camilla Krämer, Johanna Stumme, Lucas da Costa Campos, Paulo Dellani, Christian Rubbert, Julian Caspers, Svenja Caspers, Christiane Jockwitz
Type: Original Article
Abstract:
Differences in brain structure and functional and structural network architecture have been found to partly explain cognitive performance differences in older ages. Thus, they may serve as potential markers for these differences. Initial unimodal studies, however, have reported mixed prediction results of selective cognitive variables based on these brain features using machine learning (ML). Thus, the aim of the current study was to investigate the general validity of cognitive performance prediction from imaging data in healthy older adults. In particular, the focus was with examining whether (1) multimodal information, i.e., region-wise grey matter volume (GMV), resting-state functional connectivity (RSFC), and structural connectivity (SC) estimates, may improve predictability of cognitive targets, (2) predictability differences arise for global cognition and distinct cognitive profiles, and (3) results generalize across different ML approaches in 594 healthy older adults (age range: 55–85 years) from the 1000BRAINS study. Prediction potential was examined for each modality and all multimodal combinations, with and without confound (i.e., age, education, and sex) regression across different analytic options, i.e., variations in algorithms, feature sets, and multimodal approaches (i.e., concatenation vs. stacking). Results showed that prediction performance differed considerably between deconfounding strategies. In the absence of demographic confounder control, successful prediction of cognitive performance could be observed across analytic choices. Combination of different modalities tended to marginally improve predictability of cognitive performance compared to single modalities. Importantly, all previously described effects vanished in the strict confounder control condition. Despite a small trend for a multimodal benefit, developing a biomarker for cognitive aging remains challenging.
Access this article: https://doi.org/10.1007/s11357-023-00831-4

Title: Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age
Authors: Aron S. Buchman, Tianhao Wang, Shahram Oveisgharan, Andrea R. Zammit, Sonal Agrawal, Lei Yu, David A. Bennett
Type: Research Article
Abstract:

Introduction: Examining motor and cognitive decline in separate models may underestimate their associations.

Methods: In a single trivariate model, we examined the levels and rates of decline of three phenotypes, sensor-derived total daily physical activity, motor abilities, and cognition in 1007 older adults during 6 years of follow-up. In 477 decedents, we repeated the model adding fixed terms for indices of nine brain pathologies.

Results: Simultaneous rates of decline of all three phenotypes showed the strongest correlations with shared variance of up to 50%. Brain pathologies explained about 3% of the variance of declining daily physical activity, 9% of declining motor abilities, and 42% of cognitive decline.

Discussion: The rates of declining cognitive and motor phenotypes are strongly correlated and measures of brain pathologies account for only a small minority of their decline. Further work is needed to elucidate the biology underlying correlated cognitive and motor decline in aging adults.

Access this article: https://doi.org/10.1002/alz.13347

Title: The role of acute changes in mBDNF, cortisol and pro-BDNF in predicting cognitive performance in old age
Authors: Jonna Nilsson, Maria Ekblom, Marcus Moberg & Martin Lövdén
Type: Research Article
Abstract:
The interplay between biomarkers of relevance to neuroplasticity and its association with learning and cognitive ability in old age remains poorly understood. The present study investigated acute changes in plasma concentrations of mature brain-derived neurotrophic factor (mBDNF), its precursor protein (pro-BDNF), and cortisol, in response to acute physical exercise and cognitive training interventions, their covariation and role in predicting cognitive performance. Confirmatory results provided no support for mBDNF, pro-BDNF and cortisol co-varying over time, as the acute interventions unfolded, but did confirm a positive association between mBDNF and pro-BDNF at rest. The confirmatory results did not support the hypothesis that mBDNF change following physical exercise were counteracted by temporally coupled changes in cortisol or pro-BDNF, or by cortisol at rest, in its previously demonstrated faciliatory effect on cognitive training outcome. Exploratory results instead provided indications of a general and trait-like cognitive benefit of exhibiting greater mBDNF responsiveness to acute interventions when coupled with lesser cortisol responsiveness, greater pro-BDNF responsiveness, and lower cortisol at rest. As such, the results call for future work to test whether certain biomarker profiles are associated with preserved cognition in old age.
Access this article: https://doi.org/10.1038/s41598-023-35847-5

Title: Effect of situation similarity on younger and older adults' episodic simulation of helping behaviours
Authors: A. Dawn Ryan, Ronald Smitko & Karen L. Campbell
Type: Research Article
Abstract:
Similar cognitive processes enable us to remember the past (i.e., episodic memory) and simulate future events (i.e., episodic simulation). In the current study, we demonstrate an important role for previous experience when younger and older adults simulate future behaviours. Participants read short descriptions of a person in need of help in scenarios that were more familiar to either younger or older adults (e.g., dealing with dating apps vs writing a cheque). Participants either imagined helping the person or thought about the style of the story (control task), and then rated their willingness to help, scene vividness, emotional concern, and subjective use of theory of mind. Hierarchical mixed effect modelling revealed that both episodic simulation and one’s previous experience increased willingness to help, in that participants were more willing to help if they imagined helping and the situation was more familiar to them. Further, in simulated scenarios the relationship between previous experience and willingness to help was mediated by scene vividness and perspective-taking in younger adults, but only by perspective-taking in older adults. Taken together, these findings suggest that situation similarity and episodic simulation increase willingness to help, possibly via different mechanisms in younger and older adults.
Access this article: https://doi.org/10.1038/s41598-023-36189-y

Title: Neural cell state shifts and fate loss in ageing and age-related diseases
Authors: Larissa Traxler, Raffaella Lucciola, Joseph R. Herdy, Jeffrey R. Jones, Jerome Mertens & Fred H. Gage
Type: Review
Abstract:
Most age-related neurodegenerative diseases remain incurable owing to an incomplete understanding of the disease mechanisms. Several environmental and genetic factors contribute to disease onset, with human biological ageing being the primary risk factor. In response to acute cellular damage and external stimuli, somatic cells undergo state shifts characterized by temporal changes in their structure and function that increase their resilience, repair cellular damage, and lead to their mobilization to counteract the pathology. This basic cell biological principle also applies to human brain cells, including mature neurons that upregulate developmental features such as cell cycle markers or glycolytic reprogramming in response to stress. Although such temporary state shifts are required to sustain the function and resilience of the young human brain, excessive state shifts in the aged brain might result in terminal fate loss of neurons and glia, characterized by a permanent change in cell identity. Here, we offer a new perspective on the roles of cell states in sustaining health and counteracting disease, and we examine how cellular ageing might set the stage for pathological fate loss and neurodegeneration. A better understanding of neuronal state and fate shifts might provide the means for a controlled manipulation of cell fate to promote brain resilience and repair.
Access this article: https://doi.org/10.1038/s41582-023-00815-0