Dementia with Lewy Bodies
There are no approved medications for dementia with Lewy bodies (DLB) that will stop or slow the progression of the disease.
Dementia with Lewy bodies (DLB) is often described as a “while body disorder” because it can adversely affect more than just memory.
People with dementia with Lewy bodies (DLB) often have cognitive challenges. However, unlike Alzheimer’s disease, which is described as a memory disorder, physicians refer to DLB as an “executive attention” disorder. This means that DLB affects people’s ability to solve problems and think through tasks.
In some people with DLB, motor and movement problems arise first. In others, changes in cognition or memory and thinking start first and problems with motor skills or movement arise later. As the disease progresses, all patients are likely to show other symptoms, including fluctuations in their attention, hallucinations and REM sleep behavior disorder, which is where people act out their dreams.
What are the core clinical signs of DLB?
Fluctuationsin Attention
Memory Impairment
Anxiety & Depression
Constipation
Hallucinations
REM Sleep Disorder
Movement Disorder
RestingTremor
We recently spoke with several neurologists, some of whom were memory specialists and others movement disorder specialists, who were willing to share their insights into what signs they and their colleagues use to differentiate DLB from Parkinson’s and Alzheimer diseases, which may present similarly.
Select clips below to learn more:
Core Symptoms of DLB
Resting Tremor
Impairment of memory and executive function in DLB
Alzheimer's and DLB have overlapping pathology
Because symptoms of DLB are different from symptoms of Alzheimer’s disease, the SHIMMER study in patients with DLB uses different tools to measure disease progression than are used in our Alzheimer’s trials. These include:
Cognitive Drug Research (CDR) Battery:
- Records reaction time, vigilance, and power of attention
- This exam was specifically designed for clinical trials
- CDR is performed with a computer interface, using keyboard commands to measure responses
ADCS – Activities of Daily Living (ADCS-ADL):
- Captures a care partner’s impression of a patient’s functional impairment in performing activities of daily living on a 0-78-point scale
- Lower scores indicate greater functional impairmen.
Neuropsychological Inventory (NPI):
- This exam was designed to assesses delusions, hallucinations, agitation/aggression and other behavioral disturbances in people living with dementia
- The NPI has several domains, which sum to a total of 144 points
ADCS-Clinical Global Impression of Change (CGIC):
- Assesses the patient’s overall change on a 7-point scale
Combines impressions from the physician as well as the patient and their care partner - Higher scores indicate marked improvement
- Measures duration and frequency of cognitive fluctuations on a 1-16-point scale
- Higher scores indicate more severe fluctuations in cognition and attention
Clinician Assessment of Fluctuation (CAF):
- Measures duration and frequency of cognitive fluctuations on a 1-16-point scale
- Higher scores indicate more severe fluctuations in cognition and attention
Montreal Cognitive Assessment Scale (MoCA):
- Measures cognitive impairment on a 0-30-point scale
- Lower scores reflect more cognitive impairment
Unified Parkinson’s Disease Rating Scale (USPDR) Part III:
- Measures motor signs associated with parkinsonism on a 0-136-point scale
- This exam has several parts that measures 18 types of movement problems including bradykinesia (slowness), rigidity, tremor, and gait
- Higher scores reflect more motor impairment
Cognition’s Approach
Zervimesine (also CT1812) is a selective σ-2 receptor modulator currently in development for the treatment of Alzheimer’s disease and DLB.
Increasing evidence suggests that α-synuclein oligomers disrupt key cellular processes including autophagy and elicit neuronal dysfunction and loss of synapses. This, in turn, contributes to the cognitive and motor symptoms of Parkinson’s disease, DLB and other synucleinopathies.
Data indicate that the σ-2 receptor is involved in regulating several of these cellular pathways. In addition, it has been reported that a large percentage of DLB patients have both oligomers of Aβ and α-synuclein in the brain. Evidence that we and independent researchers have collected demonstrate that σ-2 receptor modulators can block the toxic effects of Aβ oligomer-induced toxicity to neurons. Together, these factors informed our decision to pursue DLB with zervimesine, with the aim of restoring normal neuronal functioning and slowing the progression of disease.
The company has been awarded a grant from the National Institute of Aging (part of the National Institutes of Health) to conduct the Phase 2 SHIMMER clinical trial, which has completed enrollment of 130 people with mild-to-moderate DLB. Results are anticipated in the fourth quarter of 2024.
- Lewy Body Dementia: Information for Patients, Families, and Professionals (NIH)
- Lewy Body Dementia: Diagnostic Symptoms (LBDA)
- Diagnosing and Managing Lewy Body Dementia: A Comprehensive Guide (LBDA)
- Views from Within: a video series (Lewy Body Resource Center)