Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.
OBJECTIVE
To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms.


METHODS
Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4β2* nicotinic cholinergic receptor binding using 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used.


RESULTS
2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p < 0.05, corrected cluster), but binding was not associated with cognition. The C group had significant inverse correlations between 2FA binding in the thalamus (left: rs= -0.55, p = 0.008; right: rs= -0.50, p = 0.02; N = 22) and hippocampus (left: rs= -0.65, p = 0.001; right: rs= -0.55, p = 0.009; N = 22) and the Trails A score. The AD group had inverse correlation between 2FA binding in anterior cingulate (left: rs= -0.50, p = 0.01; right: rs= -0.50, p = 0.01; N = 24) and Neurobehavioral Rating Scale agitation/disinhibition factor score.


CONCLUSIONS
Cholinergic receptor binding is reduced in specific brain regions in mild to moderate AD and is related to neuropsychiatric symptoms. Among healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target.
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA. Electronic address: dsultzer@ucla.edu.
David L
DL
Sultzer
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
Rebecca J
RJ
Melrose
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Hannah
H
Riskin-Jones
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Theresa A
TA
Narvaez
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Joseph
J
Veliz
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Timothy K
TK
Ando
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Kevin O
KO
Juarez
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
Dylan G
DG
Harwood
Psychiatry/Mental Health Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
Arthur L
AL
Brody
Imaging Service, VA Greater Los Angeles Healthcare Center, Los Angeles, CA; Department of Physics, University of California-Irvine, Irvine, CA.
Mark A
MA
Mandelkern
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001384:Azetidines; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism*
C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2
Alzheimer disease; PET imaging; cholinergic receptors; healthy aging