Cortical thickness mediates the effect of β-amyloid on episodic memory.
OBJECTIVE
To investigate the associations among β-amyloid (Aβ), cortical thickness, and episodic memory in a cohort of cognitively normal to mildly impaired individuals at increased risk of vascular disease.


METHODS
In 67 subjects specifically recruited to span a continuum of cognitive function and vascular risk, we measured brain Aβ deposition using [(11)C] Pittsburgh compound B-PET imaging and cortical thickness using MRI. Episodic memory was tested using a standardized composite score of verbal memory, and vascular risk was quantified using the Framingham Coronary Risk Profile index.


RESULTS
Increased Aβ was associated with cortical thinning, notably in frontoparietal regions. This relationship was strongest in persons with high Aβ deposition. Increased Aβ was also associated with lower episodic memory performance. Cortical thickness was found to mediate the relationship between Aβ and memory performance. While age had a marginal effect on these associations, the relationship between Aβ and cortical thickness was eliminated after controlling for vascular risk except when examined in only Pittsburgh compound B-positive subjects, in whom Aβ remained associated with thinner cortex in precuneus and occipital lobe. In addition, only the precuneus was found to mediate the relationship between Aβ and memory after controlling for vascular risk.


CONCLUSIONS
These results suggest strong links among Aβ, cortical thickness, and memory. They highlight that, in individuals without dementia, vascular risk also contributes to cortical thickness and influences the relationships among Aβ, cortical thickness, and memory.
From the Helen Wills Neuroscience Institute (S.V., M.W., C.M.M., N.A., W.J.J.), University of California, Berkeley; Department of Neurology (B.R.R., D.M., C.D.), University of California, Davis; School of Education and Social Policy (C.M.H.), Northwestern University; Departments of Preventive Medicine (W.M.) and Neurology (H.C.C.), University of Southern California; Center for Imaging of Neurodegenerative Diseases (M.W.W.), University of California, San Francisco.
Sylvia
S
Villeneuve
Bruce R
BR
Reed
Miranka
M
Wirth
Claudia M
CM
Haase
Cindee M
CM
Madison
Nagehan
N
Ayakta
Wendy
W
Mack
Dan
D
Mungas
Helena C
HC
Chui
Charles
C
DeCarli
Michael W
MW
Weiner
William J
WJ
Jagust
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging
D016229:Amyloid beta-Peptides