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P2‐421: TAU DEPOSITION IN THE LOCUS COERULEUS AND DOSAL RAPHE NUCLEUS CORRELATE WELL WITH CORTICAL TAU PATHOLOGY
Author(s) -
Yi Dahyun,
Byun Min Soo,
Lee Jun Ho,
Jeon So Yeon,
Byeon Gihwan,
Joung Haejung,
Lee Han Na,
Shin Seong A.,
Lee Yun-Sang,
Kim Yu Kyeong,
Sohn Chul-Ho,
Woo Jong Inn,
Lee Dong Young
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2828
Subject(s) - locus coeruleus , tau pathology , raphe nuclei , neuroscience , nuclear medicine , pathology , chemistry , psychology , medicine , nucleus , serotonin , alzheimer's disease , disease , receptor , serotonergic
Background: Reduction of gray matter (GM) volumes in numerous brain regions is part of the cognitively normal (“healthy”) aging process. Aging, even in the absence of clinically apparent cognitive deficits, is associated with cognitive change, particularly declining performance in processing speed. While some studies have reported relationships between regional GM loss and processing speed deficits in various disease states, including Huntington’s disease and Parkinson’s disease, the regional relationships between GM volumes and processing speed in healthy adults are still not well understood. Methods: We included 2293 cognitively normal participants of the Framingham heart study, aged 25 to 91 years. All subjects underwent MRI and cognitive testing, including the Trail making tests (TMT) A and B. Gray matter (GM) cortical density maps were calculated from structural T1-weighted scans. Processing speed was determined using the Trail Making Test (TMT) Difference score (TMTB – TMTA). The TMT difference score accounts for the motor speed and visual scanning components of the TMTA and has been shown to provide a reliable measure of mental processing speed and cognitive flexibility. We performed voxelwise regression of log(TMTB-TMTA) on GM density, adjusted for covariates of age, sex, education, ventricle size and total cranial volume (TCV). Significant clusters of GM association to cognition were computed from non-parametric corrections for multiple comparisons. Further analysis using bootstrap sampling with replacement (1000 iterations) examined whether these GM regions mediated the effect of age on TMT difference. Results: The caudate head and body bilaterally were significantly associated with the TMT difference score. Fig. 1 shows significant clusters of association for t1⁄4 4 (red) and 5 (yellow) in caudate regions alone. No clusters were found elsewhere. These caudate regions mediated 22% (indirect effect 1⁄4-0.08, total effect 1⁄4 -0.37, p<0.001) of the relationship between age and the TMT difference score (Fig. 2). Conclusions: In a sample of 2293 normal adults, GM density of caudate head and body significantly relate to TMT difference score, mediating the effect of age on processing speed. These results suggest a pivotal role of the caudate nucleus for processing speed in healthy aging. P2-421 TAU DEPOSITION IN THE LOCUS COERULEUS AND DOSAL RAPHE NUCLEUS CORRELATE WELLWITH CORTICALTAU PATHOLOGY Dahyun Yi, Min Soo Byun, Jun Ho Lee, So Yeon Jeon, Gihwan Byeon, Haejung Joung, Han Na Lee, Seong A. Shin, Yun-Sang Lee, Yu Kyeong Kim, Chul-Ho Sohn, Jong Inn Woo, Dong Young Lee, and the KBASE Research Group, Biomedical Research Center Seoul National University, Seoul, Republic of South Korea; Medical Research Center Seoul National University, Seoul, Republic of South Korea; Seoul National University Hospital, Seoul, Republic of South Korea; Seoul National University, Seoul, Republic of South Korea; Seoul National University College of Medicine, Seoul, Republic of South Korea; SMG-SNU Boramae Medical Center, Seoul, Republic of South Korea; Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of South Korea. Contact e-mail: dahyunyi@gmail.com