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Neurology. 2013 Sep 10;81(11):977-83. doi: 10.1212/WNL.0b013e3182a43e45. Epub 2013 Aug 9.

Neuropathologic basis of white matter hyperintensity accumulation with advanced age.

Author information

1
From the Department of Neurology (D.E.-L., J.K., L.C.S.), Veterans Affairs Medical Center, Portland, OR; and Departments of Neurology (D.E.-L., J.K., N.M., H.H.D., D.B.H., K.W., L.C.S.) and Pathology (R.W., S.G., H.T.), Oregon Health & Science University, Portland.

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 final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH 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.

PMID:
23935177
PMCID:
PMC3888199
DOI:
10.1212/WNL.0b013e3182a43e45
[Indexed for MEDLINE]
Free PMC Article
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