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August 04, 2015; 85 (5) Article

Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes

Chen-Chih Chung, Daniela Pimentel, Azizah J. Jor'dan, Ying Hao, William Milberg, Vera Novak
First published July 8, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001820
Chen-Chih Chung
From the Departments of Neurology (C.-C.C., D.P., V.N.) and Gerontology (D.P., A.J.J., Y.H., V.N.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Neurology (C.-C.C.), Shuang Ho Hospital, Taipei Medical University, Taiwan; Institute for Aging Research, Hebrew SeniorLife (A.J.J.), and New England Geriatric, Research, Education and Clinical Center–Boston Division, VA Boston Healthcare, and Department of Psychiatry (W.M.), Harvard Medical School, Boston, MA; and School of Acupuncture-Moxibustion and Tuina (Y.H.), Beijing University of Chinese Medicine, China.
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Daniela Pimentel
From the Departments of Neurology (C.-C.C., D.P., V.N.) and Gerontology (D.P., A.J.J., Y.H., V.N.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Neurology (C.-C.C.), Shuang Ho Hospital, Taipei Medical University, Taiwan; Institute for Aging Research, Hebrew SeniorLife (A.J.J.), and New England Geriatric, Research, Education and Clinical Center–Boston Division, VA Boston Healthcare, and Department of Psychiatry (W.M.), Harvard Medical School, Boston, MA; and School of Acupuncture-Moxibustion and Tuina (Y.H.), Beijing University of Chinese Medicine, China.
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Azizah J. Jor'dan
From the Departments of Neurology (C.-C.C., D.P., V.N.) and Gerontology (D.P., A.J.J., Y.H., V.N.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Neurology (C.-C.C.), Shuang Ho Hospital, Taipei Medical University, Taiwan; Institute for Aging Research, Hebrew SeniorLife (A.J.J.), and New England Geriatric, Research, Education and Clinical Center–Boston Division, VA Boston Healthcare, and Department of Psychiatry (W.M.), Harvard Medical School, Boston, MA; and School of Acupuncture-Moxibustion and Tuina (Y.H.), Beijing University of Chinese Medicine, China.
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Ying Hao
From the Departments of Neurology (C.-C.C., D.P., V.N.) and Gerontology (D.P., A.J.J., Y.H., V.N.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Neurology (C.-C.C.), Shuang Ho Hospital, Taipei Medical University, Taiwan; Institute for Aging Research, Hebrew SeniorLife (A.J.J.), and New England Geriatric, Research, Education and Clinical Center–Boston Division, VA Boston Healthcare, and Department of Psychiatry (W.M.), Harvard Medical School, Boston, MA; and School of Acupuncture-Moxibustion and Tuina (Y.H.), Beijing University of Chinese Medicine, China.
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William Milberg
From the Departments of Neurology (C.-C.C., D.P., V.N.) and Gerontology (D.P., A.J.J., Y.H., V.N.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Neurology (C.-C.C.), Shuang Ho Hospital, Taipei Medical University, Taiwan; Institute for Aging Research, Hebrew SeniorLife (A.J.J.), and New England Geriatric, Research, Education and Clinical Center–Boston Division, VA Boston Healthcare, and Department of Psychiatry (W.M.), Harvard Medical School, Boston, MA; and School of Acupuncture-Moxibustion and Tuina (Y.H.), Beijing University of Chinese Medicine, China.
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Vera Novak
From the Departments of Neurology (C.-C.C., D.P., V.N.) and Gerontology (D.P., A.J.J., Y.H., V.N.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Neurology (C.-C.C.), Shuang Ho Hospital, Taipei Medical University, Taiwan; Institute for Aging Research, Hebrew SeniorLife (A.J.J.), and New England Geriatric, Research, Education and Clinical Center–Boston Division, VA Boston Healthcare, and Department of Psychiatry (W.M.), Harvard Medical School, Boston, MA; and School of Acupuncture-Moxibustion and Tuina (Y.H.), Beijing University of Chinese Medicine, China.
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Citation
Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes
Chen-Chih Chung, Daniela Pimentel, Azizah J. Jor'dan, Ying Hao, William Milberg, Vera Novak
Neurology Aug 2015, 85 (5) 450-458; DOI: 10.1212/WNL.0000000000001820

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Abstract

Objective: The aim of this prospective study was to investigate the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes mellitus (T2DM) over a 2-year span.

Methods: Sixty-five participants (aged 66 ± 9.2 years, 35 with T2DM, 33 women) were enrolled for this 2-year prospective study. Continuous arterial spin labeling at 3-tesla MRI was used to measure global and regional cerebral perfusion and vasoreactivity. Neuropsychological measures were evaluated at the beginning and completion of the study. The associations between serum inflammatory markers, regional cerebral vasoreactivity, and cognitive functions were examined using least squares models.

Results: After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity and a decline in multiple cognitive tasks compared with baseline (p < 0.0001–0.012). In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score (r2adj = 0.35, p = 0.04), and lower global vasodilation was associated with a greater decline in executive function (r2adj = 0.6, p = 0.047). Higher serum soluble intercellular and vascular adhesion molecules, higher cortisol, and higher C-reactive protein levels at baseline were associated with greater decreases in cerebral vasoreactivity and vasodilation only in the T2DM group (r2adj = 0.16–0.53, p = 0.007–0.048), independent of diabetes control and 24-hour blood pressure. Higher glycated hemoglobin A1c levels were associated with a greater increase in vasoconstriction in the T2DM group.

Conclusions: Inflammation may further impair cerebral vasoregulation, which consequently accelerates decline in executive function and daily activities performance in older people with T2DM.

GLOSSARY

BMI=
body mass index;
BP=
blood pressure;
CASL=
continuous arterial spin labeling;
CRP=
C-reactive protein;
HbA1c=
glycated hemoglobin A1c;
Hct=
hematocrit;
HVLT-R=
Hopkins Verbal Learning Test–Revised;
IADL=
Instrumental Activities of Daily Living;
IL-6=
interleukin 6;
MAP=
mean arterial pressure;
MMSE=
Mini-Mental State Examination;
MP-RAGE=
magnetization-prepared rapid-acquisition gradient echo;
ROCF=
Rey-Osterrieth Complex Figure;
sICAM=
soluble intercellular adhesion molecule;
sVCAM=
soluble vascular adhesion molecule;
T2DM=
type 2 diabetes mellitus;
VF=
Verbal Fluency

Footnotes

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

  • Received December 19, 2014.
  • Accepted in final form April 6, 2015.
  • © 2015 American Academy of Neurology
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