Cognition

Heterogeneity in cognitive aging: Mapping intra-individual changes in episodic memory over 20 years

-Lars Nyberg
Departments of Radiation Sciences and Integrative Medical Biology, Umeå University, Sweden; Umeå Centre for Functional Brain Imaging

Episodic memory performance declines with the passage of time. Little is known about inter-individual differences in rate of change. Here we used a novel statistical approach, which took into consideration influences of attrition, to identify 15-20 years changes in memory. The initial performance level relative to an individual’s age group was factored into the analysis. Of about 1500 examined participants, who participated in 2-4 longitudinal sessions, a sub-sample was found to have an initial level that fell in the highest quartile and showed minimal decline over time. This pattern deviated from a pattern of more normative age-related decline as well as from a sub-group showing rapidly declining memory performance. In a second step, the different patterns of memory change were characterized with regard to demographic, genetic, and lifestyle factors. A subset of participants took part in structural and functional brain imaging, which will allow examination of brain traits in relation to stable cognition over time.
 

Spatial navigation experience shapes adult development of brain structure in interaction with the Brain-Derived Neurotrophic Factor (BDNF) gene. 

-Martin Lövdén
Max Planck Institute for Human Development, Germany

Individual development and aging is about the interactions between genes and environment and brain and behavior, but these interactions, and the individual differences in how these interaction play our, are poorly understood. Intervention studies carry the potential to provide information beyond the descriptive truism of development as an interaction between nature and nurture. I will report a series of studies of healthy younger and older men performing a spatial navigation task every other day over four months. These navigators display navigation-related gains in performance and stable hippocampal volumes that were maintained four months after termination of training. Control groups displayed volume decrements consistent with longitudinal estimates of age-related decline. Cortical thickness of the medial parietal lobe display navigation-related increases in younger adults. Younger navigators also displayed increases in hippocampal N-acetylaspartate (NAA) as measured with magnetic resonance spectroscopy. Unlike measures of brain volume, changes in NAA are sensitive to metabolic and functional aspects of neural and glia tissue and are unlikely to reflect changes in microvasculature. Training-induced changes in NAA were absent in carriers of the Met substitution in the Brain-Derived Neurotrophic Factor (BDNF) gene, which is known to reduce activity-dependent secretion of BDNF. Among BDNF Val homozygotes, increases in NAA were strongly related to the degree of practice-related improvement in navigation performance, and normalized to pretraining levels four months after the last training session. I conclude that changes in demands on spatial navigation can alter the individual path of changes in cortical thickness, hippocampal volume, and hippocampal NAA concentrations, confirming epidemiological studies suggesting that mental experience may have direct effects on neural integrity and cognitive performance. BDNF genotype moderates some of these plastic changes, in line with the contention that gene-environment interactions shape the ontogeny of complex phenotypes.
 

New neurons for aging brains: activity-dependent regulation and functional relevance of adult hippocampal neurogenesis

-Gerd Kempermann
CRTD – Center for Regenerattive Therapies Dresden, Germany

As an intriguing exception to the rule that the brain cannot generate new neurons, there is lifelong adult neurogenesis in the hippocampus, the “gateway to memory”. Adult neurogenesis produces low numbers of new granule cells that add to the mossy fiber connection between the dentate gyrus and CA3, a particular bottleneck in the network of the hippocampus. Our hypothesis is that new neurons are critical to the function of the dentate gyrus by allowing an activity-dependent optimization of the converging mossy fiber tract in order to cope with situations of novelty and complexity. The precursor cells that are stimulated by activity and training might build up a “neurogenic reserve” that allows flexible response to cognitive challenges in the course of life. We thus can ask how “regulation” by activity and “function” of the new neurons are connected.

Many studies have investigated the function of the hippocampus after adult neurogenesis had been suppressed or ablated. Physical exercise and environmental enrichment both increase adult neurogenesis and are additive in their effect. Despite similar net consequence on adult neurogenesis they seem to exert their effects by different mechanisms and on different target cells in the course of neuronal development. Are such differences also found in behavioral tasks that assess neurogenesis-specific functions? We use a modification of the classical Morris water maze that allows the analysis of the strategies used by the mice to navigate to the hidden platform. Thereby we can ask how new neurons might increase cognitive flexibility during the acquisition and reversal period of the task. The results of the two gain-of-function paradigms were complementary to the loss-of-function experiments. New neurons appear to be important for situations in which new information has to be incorporated into existing representations and “activity” might be the feedback stimulus that alerts the hippocampus that such situation might arise.