PET tracer exploits new way to characterize dementia

An early human trial with a new PET radiotracer has found that Alzheimer's disease and vascular dementia both lead to substantial losses of nicotinic acetylcholine receptors in the cerebral cortex. The study from Germany suggests similarities in the pathogenesis of the two diseases relating to the cholinergic system.

Dr. Osama Sabri, chair of nuclear medicine, and colleagues at the University of Leipzig discovered an overlapping relationship using fluorine-18 F-A85380 PET to examine differences in nicotinic acetylcholine receptor availability in the brains of 17 Alzheimer's disease patients and four patients with vascular dementia.

Ten cognitively normal adults were imaged as experimental controls.

As abundant receptors in the normal brain, nicotinic acetylcholine receptors play a role in attention, memory, and cognition as well as cigarette addiction. Nicotine readily binds to nAChRs, as illustrated by up to a 44% decline in F-A85380 uptake after a normal subject smoked one cigarette, said Dr. Kai Kendziorra, a nuclear medicine resident who presented the study's results at the 2006 Society of Nuclear Medicine meeting.

By focusing on nAChRs, F-18 F-A85380 may offer a new approach to dementia diagnosis. MR imaging, combined with a clinical and neurophysiological assessment, diagnoses vascular dementia. F-18 FDG-PET metabolic measurement of neuronal viability is the preferred method for diagnosing Alzheimer's disease. Experimental carbon-11 polyisobutylene (PIB) and F-18 FDDNP-PET focus on the amyloid plaque and neurofibrillary tangles associated with Alzheimer's disease.

The Leipzig pilot study found that Alzheimer's disease, vascular dementia, and mixed forms of the two conditions can all be characterized by a reduction in the availability of a4b2 subtype nicotinic receptors in the cortex, Kendziorra said. Receptor loss in the periventricular white matter was most pronounced, however, among vascular dementia patients, where a statistically significant deficit of more than 4.2 nicotinic receptors was measured. Neither pure Alzheimer's disease nor mixed Alzheimer's disease/vascular dementia showed significant reductions.

"Our results are preliminary, but one might speculate that F-A85380 may be able to image axonal integrity and thus differentiate between AD and vascular dementia," Kendziorra said.

The preliminary results also pointed to an overlapping relationship between Alzheimer's disease and vascular dementia, Sabri said. Mixed dementia involving a measurable, though not statistically significant, decline in a4b2 subtype nicotinic receptor availability in the periventricular matter was observed in four patients.

In most cases, there could be a type of dementia in which a vascular factor might play a role, Sabri said.