Emerging beta-Amyloid Pathology and Accelerated Cortical Atrophy

作者：Mattsson Niklas^*; Insel Philip S; Nosheny Rachel; Tosun Duygu; Trojanowski John Q; Shaw Leslie M; Jack Clifford R Jr; Donohue Michael C; Weiner Michael W

来源：JAMA Neurology, 2014, 71(6): 725-734.

DOI：10.1001/jamaneurol.2014.446

IMPORTANCE The effect of beta-amyloid (A beta) accumulation on regional structural brain changes in early stages of Alzheimer disease (AD) is not well understood.
OBJECTIVE To test the hypothesis that the development of A beta pathology is related to increased regional atrophy in the brains of cognitively normal (CN) persons.
DESIGN, SETTING, AND PARTICIPANTS Longitudinal clinicobiomarker cohort study involving 47 CN control subjects and 15 patients with AD dementia. All participants underwent repeated cerebrospinal fluid A beta 42 and structural magnetic resonance imaging measurements for up to 4 years. Cognitively normal controls were classified using the longitudinal cerebrospinal fluid A beta 42 data and included 13 stable A beta negative (normal baseline A beta 42 levels, with less than the median reduction over time), 13 declining A beta negative (normal baseline A beta 42 levels, with greater than the median reduction over time), and 21 A beta positive (pathologic baseline A beta 42 levels). All 15 patients with AD dementia were A beta positive.
MAIN OUTCOMES AND MEASURES Group effects on regional gray matter volumes at baseline and over time, tested by linear mixed-effects models.
RESULTS Baseline gray matter volumes were similar among the CN A beta groups, but atrophy rates were increased in frontoparietal regions in the declining A beta-negative and A beta-positive groups and in amygdala and temporal regions in the A beta-positive group. A beta-positive patients with AD dementia had further increased atrophy rates in hippocampus and temporal and cingulate regions.
CONCLUSIONS AND RELEVANCE Emerging A beta pathology is coupled to increased frontoparietal (but not temporal) atrophy rates. Atrophy rates peak early in frontoparietal regions but accelerate in hippocampus, temporal, and cingulate regions as the disease progresses to dementia. Early-stage A beta pathology may have mild effects on local frontoparietal cortical integrity while effects in temporal regions appear later and accelerate, leading to the atrophy pattern typically seen in AD.

• 出版日期2014-6