Galantamine-ER for cognitive dysfunction in bipolar disorder and correlation with hippocampal neuronal viability: a proof-of-concept study.
BACKGROUND
Many subjects with bipolar disorder experience significant cognitive dysfunction, even when euthymic, but few studies assess biological correlates of or treatment strategies for cognitive dysfunction.


METHODS
Nineteen subjects with bipolar disorder in remission, who reported subjective cognitive deficits, were treated with open-label galantamine-ER 8-24 mg/day for 4 months. Ten healthy volunteers matched for age and gender were also assessed. Mood and subjective cognitive questionnaires were administered monthly. At the beginning and the end of the trial all subjects were administered neuropsychological tests, including tests of attention (Conners CPT) and episodic memory (CVLT). Bipolar subjects underwent proton magnetic resonance spectroscopy (1H-MRS) measurements before and after treatment, healthy volunteers completed baseline 1H-MRS. We acquired 1H-MRS data at 4.0 T from voxels centered on the left and right hippocampus to measure hippocampal N-acetyl aspartate (NAA, a measure of neuronal viability) and choline containing compounds (Cho, a marker of lipid metabolism and membrane turn-over).


RESULTS
Compared to healthy volunteers, bipolar subjects had higher baseline subjective cognitive deficits and lower scores on objective tests of attention (Conner's CPT) and verbal episodic memory (CVLT). After treatment, bipolar subjects experienced significant improvement of subjective cognitive scores and on objective tests of attention (Conner's CPT) and verbal episodic memory (CVLT). In the left hippocampus NAA increased and choline (Cho) decreased in bipolar subjects during treatment.


CONCLUSIONS
Bipolar subjects had cognitive dysfunction; treatment with Galantamine-ER was associated with improved cognition and with increases in neuronal viability and normalization of lipid membrane metabolism in the left hippocampus. This study was registered on ClinicalTrials.gov (NCT00181636).
Iosifescu
Dan V
DV
The Bipolar Clinic and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. diosifescu@partners.org
Moore
Constance M
CM
Deckersbach
Thilo
T
Tilley
Claire A
CA
Ostacher
Michael J
MJ
Sachs
Gary S
GS
Nierenberg
Andrew A
AA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001714:Bipolar Disorder / Q000150:complications; D001931:Brain Mapping; D002794:Choline / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D011522:Protons; D055815:Young Adult
D002800:Cholinesterase Inhibitors; D011522:Protons; D005702:Galantamine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline