Timothy C. Hain, MD Most recent update: April 7, 2019
This is a focused review of DLB, concentrating on the aspects that are associated with dizziness.
DLB was first described in 1996. Lewy bodies are accumulations of alpha-synuclein. In this disease, accumulation of Lewy bodies is associated with a slowly progressive neurological deterioration. Lewy bodies are intracytoplasmic, spherical, eosinophilic neuronal inclusion bodies.
DLB was reported as accounting for about 15-25% of all dementia, only trailing Alzheimer's disease. However, the #2 spot has also been claimed for frontotemporal dementia, and both can't be right. The high prevalence figure for DLB was derived from neuropathological autopsy studies reported that Lewy bodies (LB) are found in the brainstem and cortex of 15-25% of elderly demented patients, making diffuse Lewy body disease the largest pathologic subgroup after Alzheimer's disease.
There may be an incidence of DLB of about 0.1% in the general population. More recently, a study from the Mayo clinic suggested that the incidence was overestimated, and instead is about 3.5/100,000 person years. (Saica et al, 2014), similar to the incidence of Parkinson's disease dementia (2.5/100,000).
In spite of an immense investment of money and national resources into finding treatment for both Alzheimer's and DLB, so far, no solution has been found.
The 4th "consensus report" was published in 2017 concerning diagnosis and management of DLB. (2017). We will refer to this as the "consensus report".
While we say "confused", perhaps it would be more accurate to say that these disorders overlap, as their definition is somewhat fuzzy.
Damage is thought to occur due to accumulation of Lewy bodies in the nervous system.
A 6-stage system has been suggested beginning with lesions in the medulla and olfactory cortex, and with progression to the cortex. Lewy bodies may also be found in sympathetic and intramural ganglia (i.e. outside the CNS). Lewy bodies are composed of alpha-synuclein.
It is currently thought that alpha-synuclein exists both as unfolded monomers, but also as folded tetramers, and the folded-tetramer is believed to lead to pathology in DLB and Parkinsonism. (Bartels, 2011). On the other hand, there is considerable evidence that tetramers are found in healthy brains, and mutations that increase monomers are associated with more disease. So these two observations appear to be mutually contradictory.
DLB is characterized by dementia associated with any two of the following three core features (see "4th consensus report"):
- 1. Fluctuating cognition (thinking) with pronounced variations in attention and alertness
- 2. Recurrent Visual hallucinations. These often involve children, little people or animals.
- 3. REM sleep behavior disorder, which may precede cognitive decline.
- 3. One or more spontaneous cardinal features of Parkinsonian signs. These may include rigidity, bradykinesia, resting tremor. There are several variants of this including
- Parkinson disease with dementia (PD)
- Parkinson disease without dementia (PDD)
Key symptoms suggestive of DLB are fluctuating cognitive impairment with episodic delirium, with prominent psychiatric symptoms, especially visual hallucinations. Parkinsonism may occur spontaneously or part of an abnormal sensitivity to neuroleptic medications.
Progressive disabling mental impairment is a mandatory requirement for diagnosis of DLB. Early on, there may be prominent deficits of tests of executive function and problem solving such as the Wisconsin Card sorting test or the Trail Making test. Later on, global impairment of mental function may blur the distinction between Alzheimer's disease where the major deficit lies in memory acquisition and consolidation. Patients with DLB decline more quickly than those with Alzheimer's disease in both mental function as well as in survival time (Olichney et al, 1998)
Further features supportive of the diagnosis are (from 4th consensus statement)
- Severe neuroleptic (antipsychotic) sensitivity
- Postural instability, repeated falls
- Syncope or other episodes of transient unresponsiveness
- Severe autonomic dysfunction (e.g. constipation, orthostatic hypotension, urinary incontinence)
- systematized delusions, apathy, anxiety, and depression
- Hallucinations in other modalities
So pretty much all of neurology with a few more specific things (such as neuroleptic sensitivity)
CT or MRI may show generalized cortical atrophy. Sleep disturbance begins with or precedes onset of dementia in most cases (Boeve et al, 1998). Nevertheless, current clinical criteria are said to fail to identify 25% or more of true cases.
Autonomic failure may also accompany DLB ( Akaogi et al, 2009). Olfactory disturbances and autonomic failure may precede the motor symptoms and onset of dementia. Sweating disturbances and orthostatic hypotension are common. Patients may present with orthostatic hypotension, and then convert into DLB. (Kaufmann et al, 2017).
Kaufmann et al (2017) also suggested that the sense of smell as quantified by the UPSIT score, differentiated DLB from MSA. The small number of MSA patients they studied had UPSIT scores in the 30's, while the small number of PD and DLB patients that they studied were about 10-25. So in other words, if your sense of smell is normal, this is a point for MSA, and if it is poor, a point for DLB. This idea needs confirmation.
DLB does not cause vertigo, but it can cause unsteadiness.
As is the case for nearly all disorders characterized by neuron death, there is yet no effective causal treatment. All treatments, aside from some investigational ones, are symptomatic.
Cholinesterase inhibitors -- increase the amount of acetylcholine, and slightly improve memory and thinking. (4th consensus
- Rivastigmine (Excelon)
Memantine (Namenda) -- reduces glutamate mediated excitotoxicity. According to the 4th consensus, the "efficacy of memantine is less clear".
Antipsychotic agents -- reduces thought disorders
- Quetiapine (Seroquel) -- this is widely used according to the 4th consensus.
- Risperidone (Risperdol)
- Olanzapine (Zyprexa)
- Anpiprazole (Ablify)
- Clozapine (Clozaril)
Antidepressants (4th consensus).
- Tetramer-stabilizing compounds slow down amyloid formation (approved in Europe, but not the US).
- genistein (a herbal product, easily available), has some activity in cell cultures that might be helpful in stabilizing alpha synuclein. In other words, it might slow down deterioration. (Trivella et al, 2010)
There are also treatments for parkinsonism (mainly dopamine agonists) and low blood pressure