Abstract
Objective: We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects. Methods: Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals. Results: There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ε4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (-10.9% and -12.4% vs -5.6% and -6.3%, and -3.5% vs -1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p < 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo = -2.0 ± 4.3, divalproex = -3.9 ± 4.0) (p = 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months. Conclusions: Divalproex treatment was associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. The long-term clinical effects of these changes are not known.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1263-1271 |
| Number of pages | 9 |
| Journal | Neurology |
| Volume | 77 |
| Issue number | 13 |
| DOIs | |
| State | Published - Sep 27 2011 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Clinical Neurology
- Arts and Humanities (miscellaneous)
Cite this
Chronic divalproex sodium use and brain atrophy in Alzheimer disease. / Fleisher, A. S.; Truran, D.; Mai, J. T.; Langbaum, J. B S; Aisen, P. S.; Cummings, J. L.; Jack, Clifford R Jr.; Weiner, M. W.; Thomas, R. G.; Schneider, L. S.; Tariot, P. N.
In: Neurology, Vol. 77, No. 13, 27.09.2011, p. 1263-1271.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic divalproex sodium use and brain atrophy in Alzheimer disease
AU - Fleisher, A. S.
AU - Truran, D.
AU - Mai, J. T.
AU - Langbaum, J. B S
AU - Aisen, P. S.
AU - Cummings, J. L.
AU - Jack, Clifford R Jr.
AU - Weiner, M. W.
AU - Thomas, R. G.
AU - Schneider, L. S.
AU - Tariot, P. N.
PY - 2011/9/27
Y1 - 2011/9/27
N2 - Objective: We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects. Methods: Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals. Results: There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ε4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (-10.9% and -12.4% vs -5.6% and -6.3%, and -3.5% vs -1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p < 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo = -2.0 ± 4.3, divalproex = -3.9 ± 4.0) (p = 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months. Conclusions: Divalproex treatment was associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. The long-term clinical effects of these changes are not known.
AB - Objective: We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects. Methods: Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals. Results: There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ε4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (-10.9% and -12.4% vs -5.6% and -6.3%, and -3.5% vs -1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p < 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo = -2.0 ± 4.3, divalproex = -3.9 ± 4.0) (p = 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months. Conclusions: Divalproex treatment was associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. The long-term clinical effects of these changes are not known.
UR - http://www.scopus.com/inward/record.url?scp=82255160648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82255160648&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318230a16c
DO - 10.1212/WNL.0b013e318230a16c
M3 - Article
C2 - 21917762
AN - SCOPUS:82255160648
VL - 77
SP - 1263
EP - 1271
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 13
ER -