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Neuropathologic basis of age-associated brain atrophy
Deniz Erten-Lyons1, Hiroko H Dodge, Randall Woltjer
1Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA. ertenlyo@ohsu.edu
JAMA Neurology
|April 5, 2013
Summary
Brain atrophy markers like ventricular volume changes are linked to Alzheimer disease and vascular pathology in older adults. These changes correlate with cognitive decline, even after accounting for brain disease severity.
Area of Science:
- Neurology
- Neuroscience
- Gerontology
Background:
- Brain volume changes are used as surrogate markers for Alzheimer disease (AD) neuropathology.
- The relationship between brain atrophy and AD pathology in aging brains requires further clarification.
Purpose of the Study:
- To investigate the association between longitudinal brain atrophy and neuropathologic features in an elderly population.
- To determine which brain volume changes best correlate with Alzheimer disease and vascular pathology.
Main Methods:
- An autopsy study of 71 elderly individuals from the Oregon Brain Aging Study.
- Magnetic resonance imaging (MRI) scans were analyzed for ventricular, total brain, and hippocampal volumes.
- Mixed-effects models assessed associations between volume trajectories and neuropathology (tangles, plaques, infarcts, amyloid angiopathy, Lewy bodies, APOE ε4) and cognitive status.
Main Results:
- Ventricular volume trajectory correlated significantly with infarcts, neurofibrillary tangles, neuritic plaques, APOE ε4, and dementia diagnosis.
- Total brain volume trajectory was associated with mild cognitive impairment (MCI).
- Hippocampal volume trajectory showed a significant association with amyloid angiopathy.
Conclusions:
- Ventricular volume changes are more sensitive indicators of accumulating AD and vascular pathology than total brain or hippocampal volumes in older adults.
- Brain volume trajectories remained associated with cognitive impairment (MCI, dementia) after controlling for neuropathology.
- Unmeasured factors may contribute to brain atrophy in individuals with cognitive impairment.
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