Dementia with Lewy bodies

Dementia with Lewy bodies (DLB), also known as Lewy body disease, is a neurodegenerative disease (a synucleinopathy to be specific) related to Parkinson disease (PD). It is reported as the second most common form of dementia following Alzheimer disease (AD), accounting for 15-20% of cases at autopsy. 

Epidemiology

Dementia with Lewy bodies presents in older patients (onset typically in 50-70 years of age), and is sporadic ^1-2,7. 

It is the second most common neurodegenerative cause of dementia in older patients, after Alzheimer disease, accounting for 15-20% of cases ^3-4,7.

Clinical presentation

Typically patients first present with a frontal-type dementia with little in the way of memory deficits early in the course of the disease. Core features include ^2,4,7:

• fluctuating cognitive impairment especially in executive function, attention and alertness
• visuospatial impairment, including visual hallucinations (detailed and vivid)
• concurrent parkinsonian symptoms may be present, but is less common, more frequently occurring years after the onset of dementia

Late in the disease quadriplegia and/or apallic syndrome may develop ².

Dementia with Lewy bodies vs Parkinson disease dementia

There are three entities to be distinguished in this gamut:

1. Parkinson disease (PD)
2. Parkinson disease dementia (PDD)
3. Dementia with Lewy bodies (DLB)

The relationship between Parkinson disease and dementia with Lewy bodies is controversial, with some authors believing they are different manifestations of the same disease, whereas others (perhaps most) believe they are distinct entities ². This notwithstanding, the main clinical distinction lies in the timing of symptoms.

In dementia with Lewy bodies, dementia precedes or accompanies parkinsonism (or at least becomes clinically evident within 12 months of presentation ⁵). Patients with Parkinson disease, on the other hand, will not infrequently also develop dementia. However, it typically occurs years after the onset of parkinsonian symptoms ^1-2,5. Such cases are then referred to as Parkinson disease dementia (PDD); at least 12 months of Parkinsonism without dementia need to precede cognitive impairment ^5,7.

Dementia with Lewy bodies vs Alzheimer disease

The prominent and fairly initially isolated memory disturbance seen early in the course of classical Alzheimer disease is the main distinguishing clinical feature.  Posterior cortical atrophy variant of Alzheimer disease is harder to distinguish especially as it shares some clinical features. 

Cognitive, movement and visual symptoms are treated with their respective medications. Treatment with neuroleptics may exacerbate Parkinsonian symptoms. Therefore a balance must be sought.  Cholinesterase inhibitors may be more effective in Lewy body disease than in Alzheimer disease.

Pathology

The characteristic feature of Lewy body disease (not surprisingly perhaps) is the accumulation of Lewy bodies throughout the brain, which results from alpha-synuclein conformation, which in turn lead to intranuclear inclusions.

Lewy bodies are seen in greatest concentrations in the midbrain, hypothalamus, basal ganglia, inferior olives, brainstem reticular formation, and dentate nuclei of the cerebellum ².

Neurofibrillary tangles are also present, although unlike those found in Alzheimer disease, they lack an amyloid core ².

Radiographic features

MRI is the modality of choice to structurally image the brain. Functional imaging with SPECT/PET is also useful.

MRI

Unfortunately the literature is replete with studies showing atrophy in various parts of the brain without a clearly identified unique pattern. Most helpful in distinguishing DLB from other entities resulting in dementia is the absence of features of other diseases.

Features reported include ^1-2,7:

• generalised decrease in cerebral volume most marked in
  • frontal lobes
  • parietotemporal regions
• enlargement of the lateral ventricles
• relatively focal atrophy of the ⁴
  • midbrain
  • hypothalamus
  • substantia innominata

Perhaps, more importantly, the hippocampi remain normal in size, helping to distinguish Lewy body disease from Alzheimer disease ^2,4.

Nuclear medicine

Occipital hypoperfusion on SPECT/PET ¹ and may aid in differentiation from other types of dementia, especially Alzheimer disease ^8-9.

Treatment and prognosis

Unlike Parkinson disease, dementia with Lewy bodies respond less readily to L-dopa and also may have severe sensitivity reactions to neuroleptic drugs, such as rigidity, reduced consciousness, pyrexia, falling, postural hypotension and collapse ³.

Lewy body dementia also responds favourably to acetylcholinesterase inhibitors ⁶.

History and etymology

Lewy body inclusions were first discovered in the early 1900s by the German-born, American neurologist Frederic Lewy ¹⁰. However, the association of dementia with Lewy bodies was first discovered in 1976 by Kenji Kosaka,a Japanese psychiatrist and neuropathologist ¹¹. 

Differential diagnosis

It is important to realise that there is significant overlap between many neurodegenerative diseases, and that a clear-cut distinction between entities is not always possible. In the case of dementia with Lewy bodies, this is particularly the case, with strong overlap between:

• Alzheimer disease
  • clinical: may occasionally have a similar clinical presentation with a frontal type dementia or posterior cortical atrophy
  • imaging: prominent involvement of hippocampi on imaging
• Parkinson disease
  • clinical: dementia is only a late feature, with parkinsonian symptoms having been present for many years ⁵
• frontotemporal lobar degeneration
  • clinical: usually younger onset, absent parkinsonian features, absent visual hallucinations
  • imaging: more pronounced frontal/temporal atrophy; left-to-right asymmetry