Tags

Type your tag names separated by a space and hit enter

Neuropathologic basis of age-associated brain atrophy.
JAMA Neurol. 2013 May; 70(5):616-22.JN

Abstract

IMPORTANCE

While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy.

OBJECTIVE

To examine the association between brain atrophy during life and neuropathology in an elderly population.

DESIGN

Autopsy study of a cohort of elderly individuals.

SETTING

Community-based population.

PARTICIPANTS

Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death.

MAIN OUTCOMES AND MEASURES

The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death.

RESULTS

Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy.

CONCLUSIONS AND RELEVANCE

Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.

Authors+Show Affiliations

Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA. ertenlyo@ohsu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23552688

Citation

Erten-Lyons, Deniz, et al. "Neuropathologic Basis of Age-associated Brain Atrophy." JAMA Neurology, vol. 70, no. 5, 2013, pp. 616-22.
Erten-Lyons D, Dodge HH, Woltjer R, et al. Neuropathologic basis of age-associated brain atrophy. JAMA Neurol. 2013;70(5):616-22.
Erten-Lyons, D., Dodge, H. H., Woltjer, R., Silbert, L. C., Howieson, D. B., Kramer, P., & Kaye, J. A. (2013). Neuropathologic basis of age-associated brain atrophy. JAMA Neurology, 70(5), 616-22. https://doi.org/10.1001/jamaneurol.2013.1957
Erten-Lyons D, et al. Neuropathologic Basis of Age-associated Brain Atrophy. JAMA Neurol. 2013;70(5):616-22. PubMed PMID: 23552688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropathologic basis of age-associated brain atrophy. AU - Erten-Lyons,Deniz, AU - Dodge,Hiroko H, AU - Woltjer,Randall, AU - Silbert,Lisa C, AU - Howieson,Diane B, AU - Kramer,Patricia, AU - Kaye,Jeffrey A, PY - 2013/4/5/entrez PY - 2013/4/5/pubmed PY - 2013/7/26/medline SP - 616 EP - 22 JF - JAMA neurology JO - JAMA Neurol VL - 70 IS - 5 N2 - IMPORTANCE: While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy. OBJECTIVE: To examine the association between brain atrophy during life and neuropathology in an elderly population. DESIGN: Autopsy study of a cohort of elderly individuals. SETTING: Community-based population. PARTICIPANTS: Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death. MAIN OUTCOMES AND MEASURES: The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death. RESULTS: Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy. CONCLUSIONS AND RELEVANCE: Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/23552688/Neuropathologic_basis_of_age_associated_brain_atrophy_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2013.1957 DB - PRIME DP - Unbound Medicine ER -