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Emerging ?-amyloid pathology and accelerated cortical atrophy.

ABSTRACT: The effect of ?-amyloid (A?) accumulation on regional structural brain changes in early stages of Alzheimer disease (AD) is not well understood.To test the hypothesis that the development of A? pathology is related to increased regional atrophy in the brains of cognitively normal (CN) persons.Longitudinal clinicobiomarker cohort study involving 47 CN control subjects and 15 patients with AD dementia. All participants underwent repeated cerebrospinal fluid A?42 and structural magnetic resonance imaging measurements for up to 4 years. Cognitively normal controls were classified using the longitudinal cerebrospinal fluid A?42 data and included 13 stable A? negative (normal baseline A?42 levels, with less than the median reduction over time), 13 declining A? negative (normal baseline A?42 levels, with greater than the median reduction over time), and 21 A? positive (pathologic baseline A?42 levels). All 15 patients with AD dementia were A? positive.Group effects on regional gray matter volumes at baseline and over time, tested by linear mixed-effects models.Baseline gray matter volumes were similar among the CN A? groups, but atrophy rates were increased in frontoparietal regions in the declining A?-negative and A?-positive groups and in amygdala and temporal regions in the A?-positive group. A?-positive patients with AD dementia had further increased atrophy rates in hippocampus and temporal and cingulate regions.Emerging A? 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? 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.

SUBMITTER: Mattsson N

PROVIDER: S-EPMC4410966 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Emerging β-amyloid pathology and accelerated cortical atrophy.

Mattsson Niklas N Insel Philip S PS Nosheny Rachel R Tosun Duygu D Trojanowski John Q JQ Shaw Leslie M LM Jack Clifford R CR Donohue Michael C MC Weiner Michael W MW

JAMA neurology 20140601 6

<h4>Importance</h4>The effect of β-amyloid (Aβ) accumulation on regional structural brain changes in early stages of Alzheimer disease (AD) is not well understood.<h4>Objective</h4>To test the hypothesis that the development of Aβ pathology is related to increased regional atrophy in the brains of cognitively normal (CN) persons.<h4>Design, setting, and participants</h4>Longitudinal clinicobiomarker cohort study involving 47 CN control subjects and 15 patients with AD dementia. All participants ...[more]

PMID: 24781145

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Dataset Information

Emerging ?-amyloid pathology and accelerated cortical atrophy.

Publications

Emerging β-amyloid pathology and accelerated cortical atrophy.

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