In vivo SPECT imaging of vesicular acetylcholine transporter using [(123)I]-IBVM in early Alzheimer's disease.
BACKGROUND
Little is known about cholinergic activity in the early stage of Alzheimer's disease. We investigated differences in the distribution of vesicular acetylcholine transporter, using [(123)I]-iodobenzovesamicol ([(123)I]-IBVM) and Single Photon Computed Tomography (SPECT), in early AD and age-matched controls.


METHODS
Sixteen subjects (8 controls, 8 AD) underwent [(123)I]-IBVM SPECT scanning, T1-weighted anatomic scan by Magnetic Resonance (MR) imaging and Mini-Mental State Evaluation (MMSE). Image analysis, using Statistical Parametric Mapping (SPM 02), involved coregistration of each SPECT image to the MR scan, followed by a spatial normalisation to the Montreal Neurological Institute standard brain and a smoothing of each SPECT image. Group effects and correlation were assessed using two sample t-tests and linear regression respectively. Atrophy difference between the two groups was assessed by voxel-based morphometry of each MR scan using two sample t-tests.


RESULTS
MMSE values were significantly different between AD and controls. Relative to controls, a significant decrease in [(123)I]-IBVM binding (47-62%) was apparent in AD subjects in cingulate cortex and parahippocampal-amygdaloïd complex. These patterns appeared to be independent of atrophied areas.


CONCLUSIONS
These results strongly suggest that a cholinergic degeneration occurs in the early stage of AD and could be involved in the impairment of the cognitive functions. Imaging of cholinergic neurons used here could be effective in identifying potential cholinergic treatment responders.
Mazère
J
J
Service de Médecine Nucléaire, CHU de Bordeaux, Hôpital Pellegrin, Place Amélie Raba Léon, Bordeaux, France. joachim.mazere@chu-bordeaux.fr
Prunier
C
C
Barret
O
O
Guyot
M
M
Hommet
C
C
Guilloteau
D
D
Dartigues
J F
JF
Auriacombe
S
S
Fabrigoule
C
C
Allard
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000523:psychology; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D008297:Male; D009483:Neuropsychological Tests; D010880:Piperidines / Q000138:chemical synthesis; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D015899:Tomography, Emission-Computed, Single-Photon; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*
D010880:Piperidines; D019275:Radiopharmaceuticals; C493459:SLC18A3 protein, human; D050494:Vesicular Acetylcholine Transport Proteins; C101021:6-iodobenzovesamicol