Dementia with Lewy bodies rises as a new blue ocean

DLB, a disease with no available method of diagnosis

Byoung-Suk Ye, Professor of Severance Hospital, “DLB is rarely diagnosed in clinical practice”

The second most common type of progressive dementia after Alzheimer's disease

Hinders the development of dementia treatment... Big pharmas show rising interest

Byoung-Suk Ye, Professor of Neurology at Severance Hospital is presenting the latest findings in dementia (Pic: Dailypharm reporter Jin-Joong Hwang

Dementia with Lewy bodies (DLB), the second most common type of neurodegenerative disease, is expected to rise as a blue ocean in the development of diagnostics and treatments for dementia.

 

DLB has the limitation of being difficult to diagnose in the field as no clear diagnostic method has been developed for the disease.

 

In the industry, the prevailing opinion is that Lewy bodies should also be considered in addition to Alzheimer's to develop more effective drugs for dementia.

 

◆No method available to diagnose Lewy bodies...additional studies needed According to industry sources on the 14th, Byoung-Suk Ye, Professor of Neurology at Severance Hospital, said, “Alzheimer’s is characterized by memory loss and is the most common cause of dementia, but it is not dementia itself.

 

DLB is the second most common cause of dementia that often accompanies Alzheimer’s, but is rarely diagnosed clinically in the field" while presenting at the Seoul Innovative Medicine Salon that was held at Korea Development Bank the day before.

 

Lewy bodies are pathologically defined by the cytoplasmic accumulation of alpha-synuclein deposited inside the patient's cerebral cortical neurons.

 

The dementia symptoms are considered to occur when the cytoplasmic accumulation of alpha-synuclein (aSyn) deposition creates Lewy bodies.

 

Alzheimer’s dementia, a representative neurodegenerative disease, and symptoms of dementia are known to be caused by beta-amyloid aggregation or hyperphosphorylated tau proteins.

 

DLB and Parkinson's disease dementia (PDD) share pathological causes.

 

In Parkinson's disease, a decline in motor function appears first, and dementia symptoms usually occur after a period of 1 to 2 years.

 

However, in DLB, a decline in cognitive function occurs first or a decline in motor function and cognitive function at the same time.

 

Characteristic symptoms of Alzheimer’s (left) and Lewy Body disease (Pic: Dailypharm reporter Jin-Joong Hwang)

Major symptoms of DLB include a decline in cognitive function, visual disorder, REM (rapid eye movement sleep) behavior disorder, autonomic nervous system abnormalities, hypersomnia, loss of smell, hallucinations, and depression.

 

Cognitive decline is more prominently shown in a loss in concentration, executive ability, and visuospatial function than in memory.

 

Also, another characteristic is the unstable decline and improvement in cognitive function.

 

On the other hand, in Alzheimer's dementia, memory relatively steadily declines.

 

As of now, no clear method exists for its diagnosis.

 

In the field, it is believed that Lewy bodies may be diagnosed using fluorodeoxyglucose (FDG)-positron emission tomography (PET).

 

However, there is no study that quantitatively proves that Lewy bodies can be diagnosed with PDG-PET.

 

With no proven diagnostic method available, there are limitations to distinguishing and diagnosing Lewy bodies in the clinical field.

 

On the other hand, as Alzheimer's is known to be caused by the deposition of beta-amyloid, it can be identified relatively easily using amyloid-PET.

 

Professor Ye said, “According to autopsy studies, 40% of patients with Alzheimer's disease also showed the pathological presence of Lewy body.

 

Unless DLB is included in the diagnostic model, there is possibility that all dementias will be considered as Alzheimer's." Also, no diagnostic method yet exists to differentiate Lewy bodies from Alzheimer's in amyloid-positive patients.

 

Professor Ye said, “When diagnosing dementia using only amyloid-PET, it is highly likely that many of the patients may have amyloid-positive and tau-negative Lewy bodies.” ◆Should consider patients with mixed dementia that may have a combined Alzheimer's, Parkinson’s, or Lewy body disease when developing a drug for dementia The reason why it is necessary to distinguish not only Alzheimer's or Parkinson's when diagnosing dementia-causing diseases, but also Lewy body disease, is that there are many cases where a mix of the three diseases appear.

 

Even if a new drug that reduces beta amyloid proteins or tau proteins is developed, if alpha-synuclein, the cause of Lewy body disease remains accumulated in the brain, it is highly likely that the new drug’s treatment effect will not appear.

 

In addition to diagnostics for Lewy body disease, a diagnostic method is also needed to distinguish mixed Alzheimer's, where a patient suffers from Alzheimer's and Lewy body disease at the same time.

 

Professor Ye emphasized, “Patients with just Alzheimer's disease and patients with mixed Alzheimer's have different natural courses and responses to drugs.

 

These patients need to be distinguished to accurately determine the effect of dementia treatments.

 

Professor Ye added, "It is important to secure real-world data (RWD) by using approved Alzheimer's treatments in clinical practice.

 

I have been explaining the importance of distinguishing Lewy bodies from other causes of dementia to large multinational pharmaceutical companies, however, the need has not been delivered well because the people in charge are not practicing on-site.

 

However, interest has been increasing recently after scholars and experts in dementia treatment overseas began to emphasize the need to distinguish Lewy body disease.