Oral Sessions: IC-O2: Normal Aging and Early Detection of Alzheimer’s Disease IC-O2-03
THE EFFECTS OF AGING ON WHOLE-BRAIN FUNCTIONAL CONNECTIVITY
Matthew Brier1, Jewell Thomas1, Liang Wang1, Tammie Benzinger2, John Morris1, Beau Ances2, 1Washington University, St. Louis, St. Louis, Missouri, United States; 2Washington University School of Medicine, St. Louis, Missouri, United States. Contact e-mail:
[email protected] Background: Alzheimer’s disease (AD) causes widespread disruptions of large-scale neural communication as measured by resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). However, healthy aging is also associated with altered rs-fcMRI, particularly in the default-mode network (DMN), but the extent of these reductions is unknown. Previous studies of healthy aging have primarily focused on a limited number of brain regions and have been cross-sectional in design Therefore it often remains difficult to differentiate early AD-related rs-fcMRI changes from healthy aging. Methods: This study investigates changes in functional connectivity in cognitively normal participants both cross-sectionally (N¼356) and longitudinally (mean follow up time ¼ 3 years, N¼95). Each participant was clinically evaluated using the clinical dementia rating scale (CDR) and determined to be cognitively normal at baseline and follow-up. rs-fcMRI was acquired and standard pre-processing procedures were used. Functional connectivity was calculated by measuring the temporal correlation between the blood oxygen level dependent time-series in two regions. We then calculated mean correlation strength within 5 networks (DMN, Dorsal Attention, Control, Salience, and Sensorimotor) and between pairs of networks. Results: Increasing age lead to decreased correlations within the DMN and salience network, as well as reduced anti-correlations between the DMN and dorsal attention network. We also noted a significant interaction of age and the presence of an APOE e4 allele in the connection between posterior cingulate cortex and medial prefrontal regions where there was a more dramatic effect of age in those with an e4 allele. Notably, the effects described in the cross-sectional cohort were replicated in the longitudinal cohort. Finally, the rate of change with respect to age was found to be comparable in both samples. Conclusions: These results demonstrate that cognitively normal aging is associated with decreases in functional connectivity in specific networks compared to a more general loss in AD. These results also demonstrate that APOE has a focal effect on changes in connectivity with age. The results are critical to the interpretation of AD studies because they will allow for the discrimination of changes due to AD compared to those simply due to advancing age. IC-O2-04
DEVELOPMENT OF WHITE MATTER LESIONS IS PRECEDED BY CHANGES IN NORMALAPPEARING WHITE MATTER
Marius de Groot, Benjamin Verhaaren, Renske de Boer, Stefan Klein, Albert Hofman, Aad van der Lugt, Mohammad Ikram, Wiro Niessen, Meike Vernooij, Erasmus University Medical Center, Rotterdam, Netherlands. Contact e-mail:
[email protected] Background: White matter lesions (WML) are considered to reflect subclinical vascular brain disease and are associated with an increased risk of dementia. It is unknown whether WML develop abruptly in previously normal brain areas, or whether tissue changes are already present before WML become apparent on MRI. We therefore investigated whether development of WML is preceded by quantifiable changes in normal-appearing white matter (NAWM). Methods: In 689 participants from the general population (mean age 67 years) we performed two MRI scans on the same 1.5T scanner (including diffusion tensor imaging (DTI) and fluid attenuation inversion recovery (FLAIR) sequences) on average 3.5 years apart. Using automated tissue segmentation, we identified NAWM at baseline. We assessed which NAWM-regions converted into WML during follow-up, and differentiated new WML into regions of WML growth and de novo WML. Fractional anisotropy (FA), mean diffusivity (MD) and FLAIR-intensity of regions converting to WML and regions of persistent NAWM were compared using a regionally matched approach. Results: Low FA, high MD and high FLAIR-intensity at baseline were associated with WML development during follow-up. Compared to persistent NAWM-regions, NAWM-regions
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converting to WML had significantly lower FA (-0.03, p
