The main themes in the current studies in the Cognitive Neuroscience of Aging Laboratory are:
Differential Aging of Brain Structure
The emphasis is on longitudinal approach to study of change and variability in the rates of change in regional brain volumes as well as regional integrity of the cerebite matter. The results of our previous studies (cross sectional comparisons and longitudinal follow-up) indicate that not all brain components age at the same rate. Association cortices, the caudate nucleus, the hippocampus and the cerebellum show steeper declines than the visual cortex, the entorhinal cortex and the pons. We are trying to identify the antecedents of change and the morifiers of the age trajectories of structural brain declines. To do so, we collect several MRI images including MPRAGE, diffusion-tensor (DTI), susceptibility-weighted (SWI), high-resolution imaging targeting the hippocampus and its sub-regions, and fluid attenuated inversion recovery (FLAIR).
Cognitive Consequences of Structural Brain Aging
Although structural changes may be separated by cognitive declines by a long time period, some links between smaller regional volumes or faster longitudinal declines of brain regions and poorer performance on cognitive tasks have been noted. For example, we found that smaller prefrontal volumes are associated with greater difficulty to abandon previously reinforced but currently maladaptive cognitive strategy (Raz et al., 1998; Gunning-Dixon & Raz, 2003). Smaller putamen and cerebellar hemispheres are linked to poorer performance on perceptual-motor task (Raz et al., 2000), and the rate of shrinkage in usually stable entorhinal cortex is associated with reduced memory performance (Rodrigue & Raz, 2006).
Modifiers of Brain Aging
- Negative Modifiers
Hypertension, even when treated and reasonably well controlled, may still exert negative influence on the brain. We observed, however, that those negative effects are limited to the executive functions and the regions of their brain substrate - the anterior part of the frontal lobes (Raz et al, 2003). Sometimes, removal of mildly hypertensive subjects from a sample reduces age-related differences. We are currently attempting to replicate these findings and to examine possible mediators of the effects of mild hypertension on brain and cognition
- Positive Modifiers
Exercise is known to alleviate some of the effects of cardiovascular risk factors on many organs and systems, including the brain.
- Genetic Modifiers
Multiple genes control complex cognitive fuinctions and their brain substrates. Naturally occuring variants of specific genes affect production and expression of neurochemical compounds that modify neuroanatomy and behavior. Although those variants account for a small percentage of individual variation in brain and cognition, they are nonetheless important contributors to the emrging pattern of individual differences in human aging. For example, COMT Val158Met polymorphism was found to affect executive functions, and in our sample, Met allele homozygotes performed better than Val allele carriers on several executive tests as well as more complex tests of fluid abilities. Selective executive functions are also affected by epsilon4 allele of ApoE polymorphisms known to increase the risk for Alzheimer's disease. We are currently examining the effects of polymorphisms associated with vascular risk and inflammatory processes as candidates for explaining age-related differences in brain and cognition. For instance, a variant in the gene that controls expression of Brain-Derived Neurotrophic Factor (BDNF) modifies memory performance in healthy adults. Notably, that variant (a met allele of the BDNF val66met polymorphism) may be more harmful to memory performance when it is combined with a modifiable vascular risk factor such as elevated (though nominally normal) blood glucose (Raz et al., 2008 Front Human Neurosci). Recently, we observed that genetic variants related to inflammation response (IL-1β and CRP) significantly increase the burden of white-matter abnormalities beyond the known effects of age and hypertension (Raz et al., 2011, Biophysica et Biochimica Acta). Hence our interest in combined or synergistic influence of genetic and physiological vascular risk factors on brain and cognition in the context of aging.
Spatial Navigation and Spatial Memory
Using standardized cognitive recall and virtual environment navigation indices, we measure age-related differences in spatial navigation and related recall with cardiovascular risk and changing neural volumetry. In addition to cross-sectional analysis, longitudinal comparisons consider change in performance and differences in re-acquisition of the navigation task and potential modifiers.
Subcortical Non-Heme Iron Accumulation
Non-heme iron has been suggested to drive intracellular reactive-oxygen species production, a factor in aging suggested by oxidative stress theories. Regional non-heme iron is estimated in vivo from single echo high resolution SWI with mathematical thresholding and multi-echo T2*. We consider the differences in non-heme iron quantities in the brain across the lifespan, potential modifiers, and cognitive outcomes.
Age-related White Matter Hyperintensities (WMH)
White matter hyperintensities (WMH) refer to signal hyperintensity on T2-weighted or fluid attenuated inversion recovery (FLAIR) MRI. WMH reflect multiple age-related pathological processes and have been implicated in declines in age-sensitive cognitive skills. We investigate the cross-sectional difference and longitudinal change of WMH, the role of vascular risk factors, and cognitive consequences.
Neural Correlates and Modifiers of Episodic Memory
Although age-related declines to memory function across the adult lifespan are well-documented, other factors such as genes, vascular risk, brain volumes, and strategy use can explain individual differences in memory beyond age alone. Additionally, older age is associated with disproportionate declines in memory for associations between items (e.g., pairs of words) in memory for items alone. Much of our recent episodic memory and aging research is focused on investigating this phenomenon.