A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology

Michael L. Alosco, Michael A. Sugarman, Lilah M. Besser, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Neil W. Kowall, Rhoda Au, Jesse Mez, Charles DeCarli, Thor D. Stein, Ann C. McKee, Ronald J. Killiany, Robert A. Stern

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Abstract

Background: White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility. Objective: This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP. Methods: The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. Results: 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p=0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p=0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps<0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps<0.04). Conclusions: This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease.

LanguageEnglish (US)
Pages1347-1360
Number of pages14
JournalJournal of Alzheimer's Disease
Volume63
Issue number4
DOIs
StatePublished - Jan 1 2018

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Leukoencephalopathies
Alzheimer Disease
Dementia
Cerebral Amyloid Angiopathy
Cerebrovascular Disorders
Arteriolosclerosis
Magnetic Resonance Imaging
Neuropathology
Autopsy
White Matter
Amyloid Plaques
Disease Progression
Atherosclerosis

Keywords

  • Alzheimer's disease
  • Alzheimer's disease neuropathology
  • cerebrovascular disease
  • dementia
  • magnetic resonance imaging
  • white matter hyperintensities

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Alosco, M. L., Sugarman, M. A., Besser, L. M., Tripodis, Y., Martin, B., Palmisano, J. N., ... Stern, R. A. (2018). A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology. Journal of Alzheimer's Disease, 63(4), 1347-1360. https://doi.org/10.3233/JAD-180017

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology. / Alosco, Michael L.; Sugarman, Michael A.; Besser, Lilah M.; Tripodis, Yorghos; Martin, Brett; Palmisano, Joseph N.; Kowall, Neil W.; Au, Rhoda; Mez, Jesse; DeCarli, Charles; Stein, Thor D.; McKee, Ann C.; Killiany, Ronald J.; Stern, Robert A.

In: Journal of Alzheimer's Disease, Vol. 63, No. 4, 01.01.2018, p. 1347-1360.

Research output: Contribution to journalArticle

Alosco, ML, Sugarman, MA, Besser, LM, Tripodis, Y, Martin, B, Palmisano, JN, Kowall, NW, Au, R, Mez, J, DeCarli, C, Stein, TD, McKee, AC, Killiany, RJ & Stern, RA 2018, 'A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology' Journal of Alzheimer's Disease, vol. 63, no. 4, pp. 1347-1360. https://doi.org/10.3233/JAD-180017
Alosco, Michael L. ; Sugarman, Michael A. ; Besser, Lilah M. ; Tripodis, Yorghos ; Martin, Brett ; Palmisano, Joseph N. ; Kowall, Neil W. ; Au, Rhoda ; Mez, Jesse ; DeCarli, Charles ; Stein, Thor D. ; McKee, Ann C. ; Killiany, Ronald J. ; Stern, Robert A. / A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology. In: Journal of Alzheimer's Disease. 2018 ; Vol. 63, No. 4. pp. 1347-1360.
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AU - Martin, Brett

AU - Palmisano, Joseph N.

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