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November 10, 2020; 95 (19) Article

Association of vascular brain injury, neurodegeneration, amyloid, and cognitive trajectory

View ORCID ProfileJi Won Han, View ORCID ProfilePauline Maillard, Danielle Harvey, Evan Fletcher, Oliver Martinez, View ORCID ProfileDavid K. Johnson, John M. Olichney, Sarah T. Farias, View ORCID ProfileSylvia Villeneuve, William Jagust, Dan Mungas, Charles DeCarli
First published July 30, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010531
Ji Won Han
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Pauline Maillard
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Danielle Harvey
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Evan Fletcher
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Oliver Martinez
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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David K. Johnson
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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John M. Olichney
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Sarah T. Farias
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Sylvia Villeneuve
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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William Jagust
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Dan Mungas
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Charles DeCarli
From the Department of Neurology (J.W.H., P.M., E.F., O.M., D.K.J., J.M.O., S.T.F., D.M., C.D.), Imaging of Dementia and Aging (IDeA) Laboratory (J.W.H., P.M., E.F., O.M., C.D.), and Division of Biostatistics, School of Medicine (D.H.), University of California at Davis; Department of Neuropsychiatry (J.W.H.), Seoul National University Bundang Hospital, Seoul National University, Seongnam, Republic of Korea; Douglas Mental Health University Institute (S.V.), McGill University, Montreal, Canada; and Helen Wills Neuroscience Institute (W.J.), University of California, Berkeley.
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Citation
Association of vascular brain injury, neurodegeneration, amyloid, and cognitive trajectory
Ji Won Han, Pauline Maillard, Danielle Harvey, Evan Fletcher, Oliver Martinez, David K. Johnson, John M. Olichney, Sarah T. Farias, Sylvia Villeneuve, William Jagust, Dan Mungas, Charles DeCarli
Neurology Nov 2020, 95 (19) e2622-e2634; DOI: 10.1212/WNL.0000000000010531

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Abstract

Objective To determine whether vascular and neurodegenerative factors influence cognition before clinically relevant Alzheimer disease pathology, we analyzed MRI measures and amyloid imaging in an ethnoracially diverse cohort of cognitively normal individuals older than 60 years.

Methods Participants (n = 154; mean age 74.15 ± 6.94; 50% female; 54% Caucasian, 22.1% Hispanic, 14.9% African American) were recruited from the University of California, Davis Alzheimer's Disease Research Center, who were cognitively normal at baseline, time of PET, and MRI, and received yearly cognitive assessment for 6.23 ± 4.16 years. Mixed model regression with random slope and intercept was calculated for episodic memory and executive function, adjusting for age, sex, education, and ethnicity.

Results Vascular burden score was associated with total white matter hyperintensity (WMH) volume (β, 0.171; 95% confidence interval [CI], 0.024–0.318). WMH volume was associated with low baseline executive function (−0.115; −0.226 to −0.003) and rate of change in memory (−0.029; −0.045 to −0.012). Hippocampal volume was associated with the rate of change in memory (0.040; 0.021–0.059) and executive function (0.024; 0.008–0.039). Continuous measures of amyloid status influenced change in memory (−0.026; −0.044 to −0.008) and executive function (−0.033; −0.046 to −0.021) independently of MRI measures.

Conclusion Vascular brain injury and neurodegeneration are associated with baseline cognitive performance and the rate of longitudinal change independent of amyloid status among community-dwelling, ethnicity diverse cognitively normal individuals, supporting the role of vascular diseases as risk factors for later-life dementia.

Glossary

Aβ=
β-amyloid;
AD=
Alzheimer disease;
ADNI=
Alzheimer's Disease Neuroimaging Initiative;
CI=
confidence interval;
CVD=
cerebrovascular disease;
DVR=
distribution volume ratio;
FLAIR=
fluid-attenuated inversion recovery;
IVD=
ischemic vascular contributions to cognitive decline and dementia;
MCI=
mild cognitive impairment;
PiB=
Pittsburgh compound B;
SENAS=
Spanish and English Neuropsychological Assessment Scale;
SUVR=
standard uptake value ratio;
TE=
echo time;
TI=
inversion time;
TR=
repetition time;
UCD ADRC=
University of California, Davis Alzheimer's Disease Research Center;
VBS=
vascular burden score;
WMH=
white matter hyperintensities

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received February 15, 2020.
  • Accepted in final form May 8, 2020.
  • © 2020 American Academy of Neurology
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