38. Brain Cholinergic Function in Dementia with Lewy Bodies and Alzheimer's Disease as Measured by Positron Emission Tomography
Hitoshi Shinotoh, Kiyoshi Fukushi, Noriko Tanaka, Akiyo Aotsuka, Tsuneyoshi Ota, Shin-ichiro Nagatsuka, Shuji Tanada, Toshiaki Irie
Keywords: positron emission tomography, cholinergic function, acetylcholinesterase, 11C-MP4A, dementia with Lewy bodies, Alzheimer's disease
Postmortem studies have demonstrated more extensive loss of cholinergic function in the cerebral cortex in dementia with Lewy bodies (DLB) than in Alzheimer's disease (AD). In the present study, we measured brain regional acetylcholinesterase (AChE) activity, an index of cholinergic function in patients with DLB and AD by positron emission tomography (PET) and a radiotracer, N-[11C]methylpiperidin-4-yl acetate (MP4A).
Seven patients with DLB (4 men and 3 women; 75+6 years; NNMS score: 13+7), 36 patients with AD (17 men and 19 women; 62+8 years; NNMS score: 17+5) and 14 normal controls (NC) (9 men and 5 women; 67+10) participated in this study. A sequence of 16 PET scans was acquired covering 40 minutes after intravenous injection of 11C-MP4A (approximately 20 mCi) in each subject. Arterial blood samples were collected 24 times in 15 minutes after tracer injection for measurement of total radioactivity and metabolite analysis. For quantification of AChE activity, a three-compartment kinetic model was employed to yield estimates of K1 (transport into tissue), k2 (tissue clearance of unchanged tracer into blood), and k3 (hydrolysis rate of [11C]MP4A by AChE, i.e. AChE activity) using the time-radioactivity curve in regions of interest in the brain and metabolite corrected arterial plasma input function.
The k3 values in the cerebral cortex were remarkably reduced by 37% in the 7 patients with DLB (p<0.001 with Bonferroni correction compared with NC), and moderately reduced by 20% in the 36 patients with AD (p<0.0001 compared with NC). The reduction of cortical k3 values in DLB patients was more severe than that in the AD patients (p<0.001).
The results suggest that the ascending cholinergic systems from the basal forebrain are more severely impaired in DLB than AD. The severe loss of cholinergic function may be related to typical symptoms such as visual hallucinations.
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