- Email: [email protected]
AMYLOID BURDEN, CORTICAL THICKNESS, AND COGNITIVE FUNCTION IN THE WISCONSIN REGISTRY FOR ALZHEIMER'S PREVENTION
P66
Poster Presentations: IC-P
greater hippocampal activation. Conclusions: MCI patients with evidence of elevated cortical amyloid-b deposition are more likely to demonstrate hippocampal hyperactivation, faster rate of hippocampal atrophy and clinical progression. Amyloid deposition and hippocampal hyperactivity both contribute to hippocampal atrophy. This is consistent with the hypothesis that amyloid accumulation may contribute to excitotoxicity with initial abnormal increases in neuronal activity and eventual neuronal loss over the course of MCI
is more pronounced in Ab+ individuals. Results: Compared to the Abgroup, the Ab+ group exhibited significant cortical thinning of the entorhinal cortex (p¼.017). Secondary analyses revealed significant negative correlations between co-localized Ab burden and cortical thickness in both the entorhinal cortex (p¼.005) and amygdala (p¼.025). The Ab+ group also tended to have more pronounced age-related cortical thinning in the parahippocampal gyrus (p¼.059). With respect to cognition, compared to the Ab- group, the Ab+ group had lower, but nonsignificant, test scores on all cognitive measures, and significantly greater age-associated cognitive decline on measures of Speed & Flexibility (p¼.034), Verbal Ability (p¼.058), and Visuospatial Ability (p¼.089). Conclusions: Our findings suggest that early Ab aggregation has deleterious effects on brain structure and cognitive function, even in midlife; and that the temporal lag between Ab deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.
IC-P-119
IC-P-118
AMYLOID BURDEN, CORTICAL THICKNESS, AND COGNITIVE FUNCTION IN THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION
MICROSTRUCTURAL WHITE MATTER CHANGES UNDERLYING COGNITIVE IMPAIRMENTS IN AMYOTROPHIC LATERAL SCLEROSIS: AN IN VIVO STUDY USING DTI
Elisabeth Kasper1, Christina Schuster2, Judith Machts3, Daniel Bittner4, Joern Kaufmann5, Stefan Vielhaber6, Reiner Benecke1, Stefan Teipel7, Johannes Prudlo1, 1University of Rostock, Rostock, Germany; 2DZNE
Benjamin Matthew Doherty1, Jennifer M. Oh2, Stephanie A. Schultz1, Rebecca L. Koscik3, N. Maritza Dowling4, Todd E. Barnhart1, Dhanabalan E. Murali1, Catherine L. Gallagher2, Cynthia M. Carlsson1, Barbara B. Bendlin5, Asenath LaRue3, Bruce P. Hermann6, Howard A. Rowley2, Sanjay Asthana7, Mark A. Sager8, Brad T. Christian1, Sterling C. Johnson9, Ozioma C. Okonkwo10, 1University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States; 2 Wisconsin Alzheimer’s Disease Research Center, Madison, Wisconsin, United States; 3University of Wisconsin-Madison, Madison, Wisconsin, United States; 4University of Wisconsin-Madison, Wisconsin, United States; 5 University of Wisconsin-Madison, Madison, Wisconsin, United States; 6 UW, Madison, Wisconsin, United States; 7UW Section of Geriatrics/Gerontology, Madison, Wisconsin, United States; 8University of Wisconsin School of Medicine, Madison, Wisconsin, United States; 9VA GRECC, Madison, Wisconsin, United States; 10University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States. Contact e-mail: [email protected] Background: The preclinical stage of Alzheimer’s disease is characterized by gradual accumulation of amyloid-b (Ab), in the absence of detectable clinical symptoms. Existing investigations on the influence of early Ab accumulation on cognitive function and brain morphometric measures have been primarily conducted in older cognitively-normal (CN) individuals. This study investigated the associations between Ab burden, cortical thickness, and cognition in younger CN individuals. Methods: Participants were 109 cognitively normal (CN) late-middle-aged adults (age range, 46.93-71.26 years) enrolled in the Wisconsin Registry for Alzheimer’s Prevention. All participants underwent PiB-PET (Siemens HR+) and anatomical T1 MR (GE 3.0T) imaging. They also completed a comprehensive cognitive exam within 6.6065.97 months of the PiB-PET scan. The cognitive test scores mapped onto six cognitive factors: Immediate Memory, Verbal Learning & Memory, Working Memory, Speed & Flexibility, Visuospatial Ability, and Verbal Ability. Participants were classified as Ab positive (Ab+) or Ab negative (Ab-) based on visual rating of PiB DVR maps. Cortical thicknesses of AD-vulnerable ROIs were obtained from MR images using FreeSurfer. Analyses of covariance, adjusting for relevant covariates, were used to investigate group differences in cortical thickness and cognitive factor scores. Finally, covariate-adjusted multiple regression models, which included age*Ab rating interactions, were used to investigate whether age-related cortical thinning and cognitive decline
Figure 1. Group comparisons of diffusivity values. Red ¼ comparison between cognitively impaired ALS-patients to healthy controls; blue: comparison between cognitively intact ALS-patients to healthy controls; FA ¼ fractional anisotropy; MD ¼ mean diffusivity; RD ¼ radial diffusivity
Poster Presentations: IC-P
greater hippocampal activation. Conclusions: MCI patients with evidence of elevated cortical amyloid-b deposition are more likely to demonstrate hippocampal hyperactivation, faster rate of hippocampal atrophy and clinical progression. Amyloid deposition and hippocampal hyperactivity both contribute to hippocampal atrophy. This is consistent with the hypothesis that amyloid accumulation may contribute to excitotoxicity with initial abnormal increases in neuronal activity and eventual neuronal loss over the course of MCI
is more pronounced in Ab+ individuals. Results: Compared to the Abgroup, the Ab+ group exhibited significant cortical thinning of the entorhinal cortex (p¼.017). Secondary analyses revealed significant negative correlations between co-localized Ab burden and cortical thickness in both the entorhinal cortex (p¼.005) and amygdala (p¼.025). The Ab+ group also tended to have more pronounced age-related cortical thinning in the parahippocampal gyrus (p¼.059). With respect to cognition, compared to the Ab- group, the Ab+ group had lower, but nonsignificant, test scores on all cognitive measures, and significantly greater age-associated cognitive decline on measures of Speed & Flexibility (p¼.034), Verbal Ability (p¼.058), and Visuospatial Ability (p¼.089). Conclusions: Our findings suggest that early Ab aggregation has deleterious effects on brain structure and cognitive function, even in midlife; and that the temporal lag between Ab deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.
IC-P-119
IC-P-118
AMYLOID BURDEN, CORTICAL THICKNESS, AND COGNITIVE FUNCTION IN THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION
MICROSTRUCTURAL WHITE MATTER CHANGES UNDERLYING COGNITIVE IMPAIRMENTS IN AMYOTROPHIC LATERAL SCLEROSIS: AN IN VIVO STUDY USING DTI
Elisabeth Kasper1, Christina Schuster2, Judith Machts3, Daniel Bittner4, Joern Kaufmann5, Stefan Vielhaber6, Reiner Benecke1, Stefan Teipel7, Johannes Prudlo1, 1University of Rostock, Rostock, Germany; 2DZNE
Benjamin Matthew Doherty1, Jennifer M. Oh2, Stephanie A. Schultz1, Rebecca L. Koscik3, N. Maritza Dowling4, Todd E. Barnhart1, Dhanabalan E. Murali1, Catherine L. Gallagher2, Cynthia M. Carlsson1, Barbara B. Bendlin5, Asenath LaRue3, Bruce P. Hermann6, Howard A. Rowley2, Sanjay Asthana7, Mark A. Sager8, Brad T. Christian1, Sterling C. Johnson9, Ozioma C. Okonkwo10, 1University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States; 2 Wisconsin Alzheimer’s Disease Research Center, Madison, Wisconsin, United States; 3University of Wisconsin-Madison, Madison, Wisconsin, United States; 4University of Wisconsin-Madison, Wisconsin, United States; 5 University of Wisconsin-Madison, Madison, Wisconsin, United States; 6 UW, Madison, Wisconsin, United States; 7UW Section of Geriatrics/Gerontology, Madison, Wisconsin, United States; 8University of Wisconsin School of Medicine, Madison, Wisconsin, United States; 9VA GRECC, Madison, Wisconsin, United States; 10University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States. Contact e-mail: [email protected] Background: The preclinical stage of Alzheimer’s disease is characterized by gradual accumulation of amyloid-b (Ab), in the absence of detectable clinical symptoms. Existing investigations on the influence of early Ab accumulation on cognitive function and brain morphometric measures have been primarily conducted in older cognitively-normal (CN) individuals. This study investigated the associations between Ab burden, cortical thickness, and cognition in younger CN individuals. Methods: Participants were 109 cognitively normal (CN) late-middle-aged adults (age range, 46.93-71.26 years) enrolled in the Wisconsin Registry for Alzheimer’s Prevention. All participants underwent PiB-PET (Siemens HR+) and anatomical T1 MR (GE 3.0T) imaging. They also completed a comprehensive cognitive exam within 6.6065.97 months of the PiB-PET scan. The cognitive test scores mapped onto six cognitive factors: Immediate Memory, Verbal Learning & Memory, Working Memory, Speed & Flexibility, Visuospatial Ability, and Verbal Ability. Participants were classified as Ab positive (Ab+) or Ab negative (Ab-) based on visual rating of PiB DVR maps. Cortical thicknesses of AD-vulnerable ROIs were obtained from MR images using FreeSurfer. Analyses of covariance, adjusting for relevant covariates, were used to investigate group differences in cortical thickness and cognitive factor scores. Finally, covariate-adjusted multiple regression models, which included age*Ab rating interactions, were used to investigate whether age-related cortical thinning and cognitive decline
Figure 1. Group comparisons of diffusivity values. Red ¼ comparison between cognitively impaired ALS-patients to healthy controls; blue: comparison between cognitively intact ALS-patients to healthy controls; FA ¼ fractional anisotropy; MD ¼ mean diffusivity; RD ¼ radial diffusivity