11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage.

BACKGROUND: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is inferred from clinical and structural imaging features. (11)C-Pittsburgh compound B (PIB) is a PET ligand that binds to beta-amyloid in extracellular plaques and vessel walls. We hypothesized that patients with a clinical diagnosis of CAA-related hemorrhage (CAAH) have increased (11)C-PIB uptake and that the pattern differs from Alzheimer disease (AD). METHODOLOGY: Patients with CAAH based on established clinical criteria were studied using (11)C-PIB PET and were compared with age-matched controls and patients with AD. Distribution volume ratio (DVR) parametric maps were created using the cerebellar cortex as a reference region. RESULTS: Twelve patients with CAAH of mean age 73.9 (range 58-93) years were compared with 22 normal controls and 13 patients with AD of mean age 71.8 (59-83) and 73.8 (56-90) years, respectively. CAAH PIB median DVR binding was higher in cortical regions (1.69, interquartile range 1.44-1.97) compared with controls (1.32, 1.21-1.44, p = 0.002) but lower than AD (2.04, 1.93-2.26, p = 0.004). The occipital-global uptake ratio was lower among patients with AD than among patients with CAAH (p = 0.008), and the frontal-global uptake ratio was higher (p = 0.012). CONCLUSION: (11)C-Pittsburgh compound B (PIB) binding is moderately increased in most patients with probable cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage. The distribution may differ from that seen in Alzheimer disease. (11)C-PIB PET may assist in the in vivo diagnosis of CAA and serve as a surrogate marker for future therapeutic studies.

Galantamine-induced improvements in cognitive function are not related to alterations in alpha(4)beta (2) nicotinic receptors in early Alzheimer's disease as measured in vivo by 2-[18F]fluoro-A-85380 PET.

INTRODUCTION: The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer's disease (AD); however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo. MATERIALS AND METHODS: 2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of approximately 200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). RESULTS: Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DV(S) before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DV(S), suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.