Cerebral amyloid angiopathy and its co-occurrence with Alzheimer's disease and other cerebrovascular neuropathologic changes

Willa D. Brenowitz; Peter T. Nelson; Lilah M. Besser; Katherine B. Heller; Walter A. Kukull

doi:10.1016/j.neurobiolaging.2015.06.028

Cerebral amyloid angiopathy and its co-occurrence with Alzheimer's disease and other cerebrovascular neuropathologic changes

Willa D. Brenowitz, Peter T. Nelson, Lilah M. Besser, Katherine B. Heller, Walter A. Kukull

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

We examined the relationship between cerebral amyloid angiopathy (CAA), Alzheimer's disease neuropathologic changes, other vascular brain pathologies, and cognition in a large multicenter autopsy sample. Data were obtained from the National Alzheimer's Coordinating Center on autopsied subjects (N = 3976) who died between 2002 and 2012. Descriptive statistics and multivariable regression models estimated the associations between CAA and other pathologies, and between CAA severity and cognitive test scores proximal to death. CAA tended to co-occur with Alzheimer's disease neuropathologic changes but a minority of cases were discrepant. CAA was absent in 22% (n = 520) of subjects with frequent neuritic plaques but present in 20.9% (n = 91) of subjects with no neuritic plaques. In subjects with no/sparse neuritic plaques, nonhemorrhagic brain infarcts were more common in those with CAA pathology than without (p = 0.007). In subjects without the APOE ε4 allele, CAA severity was associated with lower cognition proximal to death, factoring in other pathologies. The presence of CAA in patients without Alzheimer's disease may indicate a distinct cerebrovascular condition.

Original language	English
Pages (from-to)	2702-2708
Number of pages	7
Journal	Neurobiology of Aging
Volume	36
Issue number	10
DOIs	https://doi.org/10.1016/j.neurobiolaging.2015.06.028
State	Published - Oct 1 2015

Bibliographical note

Funding Information:
This study focused on CAA pathology and used data from a large multicenter database maintained by the National Alzheimer's Coordinating Center (NACC). The NACC database comprises individuals who were evaluated by one of the Alzheimer's Disease Centers (ADCs) funded by the National Institute on Aging. The primary objectives of this study were to describe (1) the co-occurrence of CAA with ADNC, particularly neuritic plaques, in autopsied older adults; (2) the clinical and pathologic features of participants with and without co-occurring CAA and neuritic plaques; and (3) the association between CAA severity and cognition adjusting for ADNC and other pathologies. This research may help identify subtypes of CAA in patients with and without AD.

Funding Information:
The NACC database is funded by NIA / NIH Grant U01 AG016976 . NACC data are contributed by the NIA -funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI David Teplow, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), and P50 AG005681 (PI John Morris, MD). This work was also supported by NIH ( R01 NS061933 , R01 NR014189 , and P30 AG028383 ).

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Alzheimer's disease neuropathologic change
Cerebral amyloid angiopathy
Cerebrovascular disease
Cognition
Neuropathology

ASJC Scopus subject areas

Neuroscience (all)
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2015.06.028

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title = "Cerebral amyloid angiopathy and its co-occurrence with Alzheimer's disease and other cerebrovascular neuropathologic changes",

abstract = "We examined the relationship between cerebral amyloid angiopathy (CAA), Alzheimer's disease neuropathologic changes, other vascular brain pathologies, and cognition in a large multicenter autopsy sample. Data were obtained from the National Alzheimer's Coordinating Center on autopsied subjects (N = 3976) who died between 2002 and 2012. Descriptive statistics and multivariable regression models estimated the associations between CAA and other pathologies, and between CAA severity and cognitive test scores proximal to death. CAA tended to co-occur with Alzheimer's disease neuropathologic changes but a minority of cases were discrepant. CAA was absent in 22% (n = 520) of subjects with frequent neuritic plaques but present in 20.9% (n = 91) of subjects with no neuritic plaques. In subjects with no/sparse neuritic plaques, nonhemorrhagic brain infarcts were more common in those with CAA pathology than without (p = 0.007). In subjects without the APOE ε4 allele, CAA severity was associated with lower cognition proximal to death, factoring in other pathologies. The presence of CAA in patients without Alzheimer's disease may indicate a distinct cerebrovascular condition.",

keywords = "Alzheimer's disease neuropathologic change, Cerebral amyloid angiopathy, Cerebrovascular disease, Cognition, Neuropathology",

author = "Brenowitz, {Willa D.} and Nelson, {Peter T.} and Besser, {Lilah M.} and Heller, {Katherine B.} and Kukull, {Walter A.}",

note = "Funding Information: This study focused on CAA pathology and used data from a large multicenter database maintained by the National Alzheimer's Coordinating Center (NACC). The NACC database comprises individuals who were evaluated by one of the Alzheimer's Disease Centers (ADCs) funded by the National Institute on Aging. The primary objectives of this study were to describe (1) the co-occurrence of CAA with ADNC, particularly neuritic plaques, in autopsied older adults; (2) the clinical and pathologic features of participants with and without co-occurring CAA and neuritic plaques; and (3) the association between CAA severity and cognition adjusting for ADNC and other pathologies. This research may help identify subtypes of CAA in patients with and without AD. Funding Information: The NACC database is funded by NIA / NIH Grant U01 AG016976 . NACC data are contributed by the NIA -funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI David Teplow, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), and P50 AG005681 (PI John Morris, MD). This work was also supported by NIH ( R01 NS061933 , R01 NR014189 , and P30 AG028383 ). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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Cerebral amyloid angiopathy and its co-occurrence with Alzheimer's disease and other cerebrovascular neuropathologic changes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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