Looking For the Earliest Signs of Lewy Body Disease Before Other Clear Symptoms Develop

Lewy body disease, which is second only to Alzheimer’s in terms of prevalent neurodegenerative diseases, can now be identified prior to the manifestation of symptoms using a spinal fluid analysis, as per findings from a research team at Lund University.

These findings, published in Nature Medicine, also revealed a strong correlation between Lewy body disease and a decreased sense of smell, often evident before other prominent symptoms emerge. These discoveries were also concurrently presented at the Alzheimer’s Association International Conference.

Often referred to collectively as Lewy body disease, Parkinson’s disease and Lewy body dementia fall under this term. The former is diagnosed when movement issues are predominant, while the latter is recognized when cognitive impairments take precedence.

According to Professor Oskar Hansson of Neurology at Lund University and a senior consultant at Skåne University Hospital, “Lewy body disease is caused by the misfolding of the alpha-synuclein protein in the brain. When this happens, the protein clumps together and forms what are called Lewy bodies, which damage the nerve cells.”

Prior to recent developments, the presence of Lewy bodies in the brain of an individual suffering from motor or cognitive impairments could only be confirmed post-mortem. The spinal fluid test now allows the detection of the misfolded protein in living patients. Professor Hansson’s research team recently concluded a comprehensive study involving over 1,100 participants, none of whom initially exhibited any cognitive or motor impairments. Yet, the spinal fluid test revealed that almost 10% had Lewy bodies present in their brains, suggesting that Lewy body disease can be detected prior to symptom onset.

Professor Hansson reported that study participants who tested positive for Lewy bodies displayed a decline in cognitive functions over time, and eventually developed Parkinson’s disease or Lewy body dementia. Moreover, it was observed that the presence of Lewy bodies was significantly linked to a reduced sense of smell, even before the development of other symptoms. This sensory degradation worsens with disease progression. The correlation is strong enough to propose routine smell testing in individuals over 60, followed by spinal fluid analysis for early detection of Lewy body disease, as per Professor Hansson.

He also noted that several medications aimed at Lewy bodies are under development, in hopes of decelerating the disease progression. These medications are likely to be most effective if administered early on, and symptom-free individuals with a diminished sense of smell and positive Lewy body tests could be ideal candidates for drug trials seeking to develop early intervention treatments.

In another study, the team examined more than 800 individuals with cognitive impairments and discovered that nearly a quarter of them exhibited test results suggestive of Lewy body disease. Roughly half of these individuals also showed accumulation of amyloid and tau proteins, typically associated with Alzheimer’s disease.

The study found that for those who had an accumulation of both amyloid and tau proteins in addition to Lewy bodies, the progression of the disease was significantly quicker. This indicates that these neural changes interact with each other, providing critical insights for prognostic prediction.

Professor Hansson believes that this Lewy body disease test will soon be incorporated into clinical procedures to enhance the diagnostic and prognostic evaluation of patients with movement disorders and cognitive symptoms.

Just as there is for Alzheimer’s, Professor Hansson is hopeful for the development of a blood test for Lewy body disease. However, one hurdle is the lower concentration of brain-originating proteins in the blood compared to spinal fluid, often 100 to 1000 times less, making the detection of Lewy body alterations challenging.

Nevertheless, Professor Hansson remains hopeful, noting that even though the possibility of a blood test for Alzheimer’s disease was doubted five years ago, it’s now a reality. As a result, significant efforts are being put into refining the methodology in anticipation of future breakthroughs.

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