Alterations in nicotinic α4β2 receptor binding in vascular dementia using ¹²³I-5IA-85380 SPECT: comparison with regional cerebral blood flow.
OBJECTIVE
To investigate differences in distribution of α4β2 subtypes of nicotinic acetylcholine receptors (nAChRs) using the ligand ¹²³I-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) and single photon emission computed tomography (SPECT) in subjects with vascular dementia and age-matched controls. ¹²³I-5IA-85380 binding was compared to corresponding regional cerebral blood flow (rCBF) changes in the same subjects.


METHODS
Thirty subjects (14 vascular dementia and 16 controls) underwent ¹²³I-5IA-85380 and rCBF ((99m)Tc-exametazime) SPECT scanning. Image analysis was performed on voxel basis using statistical parametric mapping (SPM2).


RESULTS
Compared to controls, reductions in relative ¹²³I-5IA-85380 uptake were identified in dorsal thalamus and right caudate in vascular dementia. Increase in scaled ¹²³I-5IA-85380 uptake in cuneus was also demonstrated in vascular dementia relative to controls. Perfusion deficits in anterior cingulate were apparent in the patient group and did not appear to be associated with ¹²³I-5IA-85380 changes.


CONCLUSIONS
Reduced ¹²³I-5IA-85380 uptake in vascular dementia was confined to sub-cortical regions, unlike the cortical reductions previously described in Alzheimer's disease. Elevation of normalised ¹²³I-5IA-85380 uptake in cuneus in vascular dementia could be a compensatory response to reduced cholinergic activity in dorsal thalamus.
Colloby
S J
SJ
Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. s.j.colloby@ncl.ac.uk
Firbank
M J
MJ
Pakrasi
S
S
Perry
E K
EK
Pimlott
S L
SL
Wyper
D J
DJ
McKeith
I G
IG
Williams
E D
ED
O'Brien
J T
JT
D000368:Aged; D000369:Aged, 80 and over; D001384:Azetidines / Q000493:pharmacokinetics*; D001776:Blood Circulation Time; D001931:Brain Mapping; D002074:Butanones / Q000493:pharmacokinetics; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D015140:Dementia, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
C104288:A 85380; D001384:Azetidines; D002074:Butanones; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C078058:exametazime