Metabolic patterns associated with the clinical response to galantamine therapy: a fludeoxyglucose f 18 positron emission tomographic study.
BACKGROUND
Regional brain correlates of treatment with cholinesterase inhibitors in those with Alzheimer disease are unknown.


OBJECTIVE
To map brain metabolism associated with the treatment response to galantamine with fludeoxyglucose F 18 positron emission tomography in patients with Alzheimer disease.


METHODS
This is a hypothesis-driven, prospective, open-label study of 19 patients with mild to moderate Alzheimer disease examined before and after treatment with the cholinesterase inhibitor galantamine. Clinical examinations included the cognitive portion of the Alzheimer Disease Assessment Scale, the Mini-Mental State Examination, and the Neuropsychiatric Inventory. Imaging was performed using fludeoxyglucose F 18 positron emission tomography. The positron emission tomographic data, registered to a probabilistic anatomical atlas, were subjected to a voxel-based analysis of 3 subgroups: total patient analysis, cognitive analysis, and behavioral analysis. Subvolume thresholding corrected random lobar noise to produce 3-dimensional significance maps.


RESULTS
The total group analysis showed an increase in left caudate metabolism with no significant change in clinical outcomes for the total group with treatment. Subgroup analysis of cognitive and behavioral responders demonstrated a significant activation of a striatal-thalamofrontal network with galantamine treatment that was not present in patients whose condition worsened or was unchanged by therapy. In cognitive subgroups, change in left anterior cingulate metabolism significantly correlated with change in the cognitive portion of the Alzheimer Disease Assessment Scale (r = 0.70, P = .02); in behavioral subgroups, right cingulate metabolic change significantly correlated with improvement in depression and right ventral putamen metabolic change with improvement in apathy (r = 0.63, P<.05 for both).


CONCLUSIONS
Cognitive and behavioral responders to galantamine therapy show clinically related improvements in prefrontal network metabolism along with thalamic activation.
Mega
Michael S
MS
Alzheimers Disease Center and Center on Aging, Providence Health System, Portland, OR 97222. michael.mega@providence.org
Dinov
Ivo D
ID
Porter
Verna
V
Chow
George
G
Reback
Erin
E
Davoodi
Paras
P
O'Connor
Susan M
SM
Carter
Michele F
MF
Amezcua
Herminia
H
Cummings
Jeffrey L
JL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D001526:Behavioral Symptoms / Q000188:drug therapy; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects; D005260:Female; D019788:Fluorodeoxyglucose F18; D007839:Functional Laterality; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D016896:Treatment Outcome
D018697:Nootropic Agents; D019275:Radiopharmaceuticals; D005702:Galantamine; D019788:Fluorodeoxyglucose F18