Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study.
Mild cognitive impairment (MCI) often represents an early form of Alzheimer disease (AD). In both MCI and AD, characteristic cholinergic changes may occur. Functional magnetic resonance imaging (fMRI) may help to examine neurochemical changes in early disease by studying signal reactivity to pharmacological challenge. In this study, MCI patients [n=28; mean age 73.6+/-7.5; mini mental state examination (MMSE) 27.0+/-1.2] were scanned during task performance in a randomized trial under three different medication regimes: at baseline [BL; no galantamine (GAL)], after a single oral dose of GAL (SD), and after prolonged exposure (steady state: SS). Memory tasks included an episodic face-encoding task and a parametric n-letter back working memory (WM) task. Alterations in brain activation patterns before and after treatment were analyzed for both tasks using multilevel statistical analysis. Significant increases in brain activation from BL were observed after prolonged exposure only. For face encoding (n=28), these involved left prefrontal areas, the anterior cingulate gyrus, left occipital areas, and left posterior hippocampus. For working memory (n=28), increased activation was found in right precuneus and right middle frontal gyrus, coinciding with increased accuracy scores after GAL treatment. In conclusion, cholinergic challenge produces alterations in brain activation patterns in elderly MCI patients that can be detected with fMRI. This should encourage further functional imaging studies to examine the status of neurotransmitter systems in disease.
Goekoop
Rutger
R
Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands. R.Goekoop@vumc.nl
Rombouts
Serge A R B
SA
Jonker
Cees
C
Hibbel
Anneke
A
Knol
Dirk L
DL
Truyen
Luc
L
Barkhof
Frederik
F
Scheltens
Philip
P
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects; D002799:Cholinergic Fibers / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy*; D004292:Dominance, Cerebral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005702:Galantamine / Q000627:therapeutic use*; D006179:Gyrus Cinguli / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008134:Long-Term Care; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000187:drug effects*
D005702:Galantamine