Greater Microstructural Integrity Research Articles

IMG-04. ASSOCIATION BETWEEN MICROSTRUCTURAL INTEGRITY OF BRAIN SUBSTRUCTURES AND NEUROCOGNITIVE OUTCOMES: A MULTI-TRAJECTORY ANALYSIS IN CHILDHOOD BRAIN TUMOR SURVIVORS

Abstract BACKGROUND The relationship between the brain’s microstructural integrity and neurocognitive outcomes is not well characterized in childhood brain tumor survivors. In healthy children, mean diffusivity (MD) generally decreases and fractional anisotropy (FA) increases with age as the brain progressively myelinates and develops. Increasing MD and decreasing FA is suggestive of microstructural injury. We investigate the association between longitudinal neurocognitive outcomes and change in MD and FA in childhood brain tumor survivors. METHODS Patients diagnosed with a brain tumor at < 20 years of age with ≥ 2 neurocognitive assessments and paired DTI at each neurocognitive timepoint were retrospectively identified and eligible for inclusion. Multi-trajectory modeling was applied to cluster patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed and working memory. Linear mixed models were used to determine whether the clusters were associated with change in MD and FA over time. RESULTS A total of 61 patients were eligible with 151 neurocognitive assessments paired with DTI. Mean follow-up was 4.8 years. Multi-trajectory modeling identified two clusters of patients with distinct neurocognitive trajectories. Compared to the low-performance group, the high-performance group (45.5%) had higher baseline neurocognitive scores with less decline in all neurocognitive outcomes. The high-performance group was also associated with a greater decrease in MD and greater increase in FA of the hippocampus and several white matter tracts such as the corpus callosum, pontine crossing tract, anterior limb of the internal capsule and inferior cerebellar peduncle, after adjusting for age and sex (all p<0.05). Additionally, the high-performance group was associated with a greater increase in FA in the superior, middle and inferior frontal gyri (all p<0.05). CONCLUSIONS The high-performance neurocognitive group was associated with greater microstructural integrity over time in multiple brain substructures compared to the low-performance group, as measured by change in fractional anisotropy and mean diffusivity.

White Matter Integrity Is Associated With Intraindividual Variability in Neuropsychological Test Performance in Healthy Older Adults.

Inconsistency of performance across neuropsychological testing instruments (dispersion) shows sensitivity to acquired injury and neurodegenerative pathology in older adults. The underlying neural correlates have remained speculative however, in spite of known white matter degradation seen in conjunction with elevated inconsistency in related operationalizations of intraindividual variability. Consistently, these operationalizations have controlled for artifactual age-related variance to increase measurement sensitivity of CNS dysfunction. In this study, dispersion was examined alongside composite scores of memory and executive functioning from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Forty-four healthy older adults (M = 72.0, SD = 6.4) underwent Diffusion Tensor Imaging (DTI) and neuropsychological testing spanning a range of cognitive domains. The results replicated previous findings, demonstrating reduced microstructural integrity with advanced age and increased integrity in high memory and executive functioning performers, across all major white matter tracts. With age first regressed from the composite scores, significant associations remained between greater executive functioning scores and greater microstructural integrity in the genu of the corpus callosum, right anterior corona radiata, anterior, posterior and rentrolenticular parts of right internal capsule, as well as right posterior thalamic radiation. With age regressed from the dispersion scores, greater values were primarily associated with decreased white matter integrity in the body and genu of corpus callosum, anterior corona radiata bilaterally and left superior longitudinal fasciculus. Dispersion is easily computed across speeded and accuracy-based measures and shows promise in detecting white matter damage, beyond that seen in the typical aging process. This appears to be the first investigation of neural correlates associated with increased dispersion.

Physical Activity Predicts Microstructural Integrity in Memory-Related Networks in Very Old Adults

Although the beneficial effects of physical activity (PA) on memory and executive function are well established in older adults, little is known about the relationship between PA and brain microstructure and the contributions of physical functional limitations and chronic diseases. This study examined whether higher PA would be longitudinally associated with greater microstructural integrity in memory- and executive function-related networks and whether these associations would be independent of physical function and chronic diseases. Diffusion tensor imaging was obtained in 2006-2008 in 276 participants (mean age = 83.0 years, 58.7% female, 41.3% black) with PA (sedentary, lifestyle active, and exercise active) measured in 1997-1998. Gait speed, cognition, depressive symptoms, cardiovascular and pulmonary diseases, hypertension, stroke, and diabetes were measured at both time points. Mean diffusivity and fractional anisotropy were computed from normal-appearing gray and white matter in frontoparietal and subcortical networks. Moderating effects of physical function and chronic diseases were tested using hierarchical regression models. Compared with the sedentary, the exercise active group had lower mean diffusivity in the medial temporal lobe and the cingulate cortex (β, p values: -.405, .023 and -.497, .006, respectively), independent of age, sex, and race. Associations remained independent of other variables, although they were attenuated after adjustment for diabetes. Associations between PA and other neuroimaging markers were not significant. Being exercise active predicts greater memory-related microstructural integrity in older adults. Future studies in older adults with diabetes are warranted to examine the neuroprotective effect of PA in these networks.