Overview
Major or Mild Neurocognitive Disorder due to Lewy Bodies (NCDLB) is a neuropsychological disorder characterised by neurocognitive impairments. These impairments are caused due to the presence of a phenomena called Lewy Bodies.
Presence of Lewy Bodies may play out in two ways, either, the person will show symptoms of Dementia or the person may show an onset of Parkinsonism and the dementia related symptoms may turn up later on. However, the causal mechanism remains the same.
Neurocognitive degeneration can be seen when the person has difficulties in attention span, exhibits executive dysfunction, learning and memory, social cognition, etc. In NCDLB, deficits in the cognitive domains are specifically seen in complex attention tasks and executive function.
As the disease progresses, visual hallucinations, emotion related issues and REM sleep behaviour disorder are also present.
In NCDLB, the deficits can be major or mild. This distinction is based on the impairment and the level of assistance required for the person to carry out day to day activities.
Major deficits mean greater impairment and assistance with most basic day to day activities while mild deficits mean lesser assistance and the person can carry out basic day to day activities.
The onset of this disease is usually sudden. Cognitive deficits are seen prior to other motor and dementia related deficits. However, the symptoms keep changing and fluctuating over time.
As the disease gets progressively worse, cognitive functions decline and visual hallucinations and dementia related symptoms start to show up. Clinical cases show mortality rates of 5-7 years after onset of the disease.
The trajectory that Lewy Bodies follow is similar to Parkinsonโs Disease. Both are related to high rates of deposits of Alpha-synuclein protein causing clumps in individual brain cells leading to neuronal death.
However, the differentiating factor between the two is the onset of symptoms. In Parkinsonโs Disease, the cognitive symptoms usually occur a year after the motor symptoms.
This may be due to damage in the temporal regions of the brain. While in NCDLB, damage can be seen in the subcortical regions.
Genetic variants have been found as the substantial cause for this disease. Mutations on SNCA genes are commonly identified for the presence of Lewy Bodies in patients with LBD and Parkinsonโs Disease with Lewy Bodies.
Common Signs and Symptoms
Common signs and symptoms include:
- Neurocognitive deficits as seen on tasks of complex attention, executive function, attention, language and memory. Confusion, forgetfulness, lack of consequential thinking are also common.
- Motor deficits can be seen in the form of rigidity of muscles, slowing movements, poor posture, loss of balance, difficulty swallowing, reduced coordination, etc.
- Mood related symptoms include irritability, depression, apathy, restlessness, anxiety.
- Delusions, visual hallucinations and paranoia are also present as the disease progresses.
- Presence of REM Sleep Behaviour Disorder should also be noted.
Risk Factors
There are no lifestyle factors associated with the risk of developing NCDLB. However, genetic factors that apply to the onset of Parkinsonism are also related to the development of this disease.
Mutations on the gene SNCA and LRRK2 are often associated with the development of this disorder.
Diagnosis
Diagnosis for this disorder is generally given by a neuropsychologist, neuropsychiatrist or a neurologist. Performance on neuropsychological test batteries as well as clinical examinations of cognitive functions is carried out to determine the severity of the disorder.
Brain imaging, polysomnography and cerebrospinal fluid testing are some medical procedures associated with the diagnosis of Parkinsonโs. Dopamine Transporter test (DatScan), SPECT or PET may be carried out.
To be diagnosed with Lewy Bodies, following criteria must be met:
- Neurocognitive dysfunction characterised by problems in executive functioning, language and memory. Progression of the disease leads to hallucinations and delirium.
- Speech related issues.
- Motor dysfunction characterised by bradykinesia, loss of automatic movements, balance and posture issues, digestion issues, etc.
- Mood alterations causing depression, irritability or apathy.
- Presence of REM Sleep Behaviour Disorder should also be noted.
Neuropsychologists are required to rule out other medical conditions or substance use that may cause similar symptoms.
Treatment
There is no cure for Lewy Bodies. However, symptomatic treatment is possible. Treatment is given according to symptom categories of Dementia Lewy Bodies or Parkinson Disease Dementia.
In cases where Parkinsonโs Disease symptoms are visible treatment is along the lines of what is suggested for Parkinsonโs Disease. Since Parkinsonโs is caused due to dopaminergic cell loss. Pharmacological treatment is often directed towards increasing levels of dopamine.
Since dopamine cannot be administered directly, medication that mimics the same effect or inhibits dopamine oxidative metabolism may be administered. Levodopa is one of the most effective medications for the treatment of Parkinsonโs Disease.
Other medication includes dopamine agonists that mimic dopamine release in the system. This group includes pergolide, pramipexole dihydrochloride, ropinirole hydrochloride, rotigotine, and apomorphine hydrochloride. They often come with a host of side effects such as hypersexuality, sleep disturbances, gambling, etc.
Cognitive impairment is often treated with cholinergic agents. Donepezil, rivastigmine, or galantamine are commonly used for the treatment of cholinergic deficits. Serotonin Reuptake Inhibitors are often administered to alleviate depression, anxiety and other mood related symptoms.
Other symptoms such as hallucinations and other psychosis symptoms are generally treated with Pimavanserin, a serotonin inverse agonist.
Differential Diagnosis
1. Major or mild neurocognitive disorder due to Parkinsonโs disease: A key differentiating feature in clinical diagnosis is the sequence in which the parkinsonism and the NCD appear.
For NCD due to Parkinson’s disease, the individual must develop cognitive decline in the context of established Parkinson’s disease; the decline should not reach the stage of major NCD until at least 1 year after Parkinson’s is diagnosed.
Comorbidity
Lewy body pathology frequently coexists with Alzheimer’s disease and cerebrovascular disease pathology, particularly among the oldest age groups.
Specialist
A neurologist, neuropsychologist or neuropsychiatrist are often referred to for treatment.