Neuropathologic basis of white matter hyperintensity accumulation with advanced age

Deniz Erten-Lyons, Randall (Randy) Woltjer, Jeffrey Kaye, Nora Mattek, Hiroko Dodge, Sarah Green, Huong Tran, Diane Howieson, Katherine Wild, Lisa Silbert

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Objective: To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. Methods: Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p <0.1. Results: Mean age at death was 94.5 years (5.5 SD). In the finalmixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increasedWMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). Conclusion: Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter.

Original languageEnglish (US)
Pages (from-to)977-983
Number of pages7
JournalNeurology
Volume81
Issue number11
DOIs
StatePublished - Sep 10 2013

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Alzheimer Disease
Arteriolosclerosis
Pallor
Atherosclerosis
Pathology
Myelin Sheath
Cerebrovascular Trauma
Magnetic Resonance Imaging
Wallerian Degeneration
Lacunar Stroke
Neurofibrillary Tangles
Amyloid Plaques
Blood Vessels
Autopsy
Ischemia
White Matter
Alzheimer's Disease
Age at Death
Vessel
Integrity

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Neuropathologic basis of white matter hyperintensity accumulation with advanced age. / Erten-Lyons, Deniz; Woltjer, Randall (Randy); Kaye, Jeffrey; Mattek, Nora; Dodge, Hiroko; Green, Sarah; Tran, Huong; Howieson, Diane; Wild, Katherine; Silbert, Lisa.

In: Neurology, Vol. 81, No. 11, 10.09.2013, p. 977-983.

Research output: Contribution to journalArticle

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