Imaging technique can differentiate Alzheimer’s disease from Lewy body dementia

Scientists in Portugal and the United Kingdom have been able to confirm that an imaging technique that traces a neuronal dopaminergic deficit in the brain is able to differentiate, in vivo, dementia with Lewy

This could have important implications for the specific management and treatment of these conditions.

American actor Robin Williams had a neurodegenerative brain disease called Lewy Body Dementia (DLB): a distressing disease, with symptoms common to Alzheimer’s disease (AD) and Parkinson’s disease (PD).

But unlike these two conditions, DLB also causes prominent mood and cognitive swings, sleep disturbances, and vivid, sometimes terrifying visual hallucinations.

It is now believed that Robin Williams, whose diagnosis was not confirmed until after death, was likely driven to suicide, in 2014, by the terrifying hallucinatory experiences he endured for years – and which he failed to experience. never spoke to anyone, not even his wife.

Susan Schneider Williams told the tragic story in a newspaper op-ed Neurology, in 2016, under the title “The terrorist in my husband’s brain”.

DLB is a newcomer to the dementia landscape. It is frequently confused by doctors with Alzheimer’s disease, but also dementia associated with Parkinson’s disease (PDD), which can affect a large number of parkinsonian patients, up to 80%, on average 10 years after the onset of Parkinson’s disease.

DLB was first identified in 1910, when a German-born American neurologist, Frederic Henry Lewy, observed in the autopsied brains of patients with Parkinson’s disease and dementia “clumps” of an unusual protein (the Alzheimer’s brains also have protein clumps, but the proteins involved are different). However, it is only recently that Lewy body dementia has been recognized as a common type of dementia.

“It is the second most frequent cause of degenerative dementia in the elderly (15 to 25% of cases at autopsy)” after Alzheimer’s disease, writes an international team – including scientists from the Champalimaud Center for ‘unknown (CCU) in Lisbon, Portugal – in a new study published on February 5, 2021 in the Journal of Neurology, Neurosurgery and Psychiatry (a publication of British medical journal group).

For several years, explains Durval Costa – lead author of the new study and head of the radiopharmacology laboratory of Champalimaud’s experimental clinical research program – it was hypothesized that the use of an imaging technique called SPECT (tomography by single-photon emission), combined with the intravenous injection of a radioactive compound, [¹²³I]FP-CIT, should make it possible to distinguish Lewy body dementia from Alzheimer’s disease.

This is due to the fact that [¹²³I]FP-CIT binds to dopamine transporters (dopamine is a neurotransmitter) located on the membrane of dopamine-producing neurons which are very abundant in a specific part of the brain called the striatum.

Since the striatal dopamine-producing neurons are depleted in Lewy body dementia (just as they are in Parkinson’s disease), but not in Alzheimer’s disease, it was natural to assume that the distribution pattern of this compound in patients’ brains, revealed by its radioactive emissions (picked up by a special camera), would then allow physicians to visually distinguish, and quantitatively accurately, DLB from AD.

The results now presented by the team last for more than twenty years.

“The imaging data were acquired around 1996-1999,” explains Francisco Oliveira, who works at Durval Costa’s laboratory and is the first author of the new article.

These patients were followed from their initial clinical diagnosis (including collection of images) until their death – in some cases for about 20 years. “

Francisco Oliveira, first author of the study

Part of the same team had already published preliminary results in 2002 in the same journal which has now published the new quantitative results. “We didn’t have all the data at the time,” notes Durval Costa. “Now we are doing it.

Due to the fact that postmortem material from the patient cohort was not yet fully available, they had not been able to compare the in vivo diagnosis with autopsy reports in a sufficient number of patients.

And, for the first time, autopsies confirm the imaging data with very high precision: the images obtained not only differentiate DLB from AD but also DLB from Parkinson’s disease (including [¹²³I]The FP-CIT distribution models are also different from each other).

Going back to Robin Williams’ last excruciating years, it should be noted that his doctors eventually diagnosed him with Parkinson’s disease, even though he and his wife were certain that something was seriously wrong with him.

“Being able to make these quantitative distinctions between diseases is essential,” says Francisco Oliveira. “These diseases can present with overlapping symptoms, making clinical diagnosis difficult in some cases and giving rise to a considerable percentage of misdiagnosis. Studies have shown that patients with DLB are frequently clinically diagnosed like MA “.

This could lead to poor patient management. The management of patients with Alzheimer’s disease is different from that of patients with DLB. Patients with DLB are very sensitive to certain types of drugs which should be avoided as they lead to faster deterioration and death.

“Our results can have a significant impact for both patients and caregivers,” adds Francisco Oliveira. “In addition, the selection of patients for clinical trials can now be done with more precise biomarkers.” The scientists also hope that in the future, their quantitative technique may also help differentiate dementia PD patients with dementia (PDD) from patients with DLB, as they may benefit from different treatment strategies.