New Research Definition of Mild Cognitive Impairment with Lewy bodies (MCI-LB)

Most people with Lewy body dementia (LBD) will experience mild changes in thinking; over time, these symptoms, referred to as mild cognitive impairment (MCI), worsen and may become dementia. As the understanding of LBD has grown, people in this pre-dementia stage are being included in research studies.

LBD is an umbrella term for two related disorders: dementia with Lewy bodies (DLB) and Parkinson’s disease dementia. Although MCI in Alzheimer’s disease and Parkinson’s disease have both been well-described for some time, defining MCI in DLB has not been formally defined. A global panel of experts in DLB has just published the first formal research criteria to aid in the study of the MCI stage of DLB, referred to as MCI with Lewy bodies (MCI-LB).

The authors also outline two lesser-known, but potentially important patterns of DLB onset that need further study. For some people the earliest sign of possible DLB is a sudden onset of confusion, like cloudy thinking, episodes of daytime sleepiness and disorientation, similar to delirium. A different subset of people may have psychiatric features like depression and hallucinations that may precede cognitive changes. This suggests a possible psychiatric-onset of DLB.

The authors stress that these new proposals require further testing in research studies before being adopted for wide clinical use; they carefully evaluate available evidence and suggest where new advances might be made.

MCI with Lewy bodies

The new research criteria describe how to categorize possible and probable MCI-LB, based on specific combinations of MCI, other DLB symptoms and abnormal biomarker test results. MCI-LB requires an observed change in cognition made by the person themselves, a close friend or family member, or their healthcare professional. The individual still maintains their prior level of independence, though more effort or time may be needed to carry out certain tasks.
An objective assessment must confirm a decline in one or more cognitive domains, such as language, attention or memory. The cognitive changes in the MCI-LB criteria are similar to DLB, but less pronounced. These typically involve difficulties with attention and doing complex mental tasks like multi-tasking and problem solving. The person may not be able to process visual input correctly, including spatial orientation or recognizing objects correctly due to lighting/shading or angle of view. Some individuals with MCI-LB may present with only memory loss, which is also seen in early Alzheimer’s disease.

In addition to MCI, one or more of the core features of DLB are required for a diagnosis of MCI-LB. These include cognitive fluctuations, well-formed visual hallucinations, REM sleep behavior disorder, and/or slow or stiff movements (parkinsonism). Other DLB symptoms can support the diagnosis, such as autonomic dysfunction (e.g. episodes of severely low blood pressure, increased salivation).

Three ‘indicative biomarkers’ of DLB are also proposed for MCI-LB. Autopsy studies confirm these tests reflect underlying Lewy body disease pathology. The biomarkers are dopamine transporter (DAT) imaging, polysomnogram to confirm REM sleep behavior disorder, and a cardiac scan to assess nerve function called MIBG scintigraphy. The authors note that these tests may not be as sensitive at detecting the MCI stage of DLB as they are at detecting the dementia stage. As such, a normal biomarker test result does not exclude MCI-LB from consideration.

The authors also suggest new, promising biomarkers with potential to improve MCI-LB diagnosis. Such tests include sophisticated measures of alpha-synuclein and other related proteins in body fluids like saliva, plasma and cerebrospinal fluid. Peripheral nervous tissue from skin biopsy, analysis of gait (walking) pattern, or changes in color vision may also be helpful. These tests can now be investigated further, as the MCI-LB criteria enable research participants to be recruited in a standardized way.

Differentiating MCI-LB from MCI in Parkinson’s disease

Cognitive profiles in Parkinson’s disease and DLB have considerable similarity, given their shared underlying disease biology. As such, separating MCI-LB from in Parkinson’s disease requires special consideration. The authors suggest a 1-year rule may be useful, similar to how Parkinson’s disease and DLB are separated. If MCI starts a year or more before the onset of changes in movement result in a Parkinson’s disease diagnosis, for research studies this will be labeled MCI-LB. If Parkinson’s disease is present for more than 1 year prior to the development of MCI, then Parkinson’s disease MCI would be the appropriate diagnosis.

The underlying biological change in both DLB and Parkinson’s disease is called Lewy body disease. These changes are thought to develop a decade or more before symptoms begin. When early symptoms later suggest the person will develop DLB in the future, this is called the prodromal stage. It is not yet clear why some people with Lewy body disease develop DLB while others develop PD. The authors recommend the term ‘prodromal Lewy body disease’ be used in research studies for individuals who have both changes in movement (parkinsonism) and mild cognitive impairment, but do not meet the criteria for Parkinson’s disease. Further research is needed to understand why and how prodromal Lewy body disease later evolves into different clinical entities.

Delirium-onset DLB

Studies suggest delirium is a possible warning sign of impending DLB, as it occurs more frequently before the onset of dementia in DLB than in Alzheimer’s disease. After diagnosis, people with DLB are hospitalized more frequently for delirium than those with AD. One study of people experiencing prolonged delirium revealed 32% had a DLB-like pattern on FDG-PET imaging. The researchers propose that delirium prior to dementia be explored as possible prodromal DLB; this is especially important in cases where there are no other identifiable medical factors provoking the delirium, or if delirium is prolonged or reoccurs.

Psychiatric-onset DLB

A significant psychiatric disorder may precede cognitive changes in a subset of people with DLB, including late-onset major depressive disorder or late-onset psychosis. Symptoms experienced may include visual hallucinations (and/or hallucinations in other senses), delusions (including Capgras syndrome), apathy, anxiety and depression. Other symptoms that may occur include cognitive changes, slowed speech, resting tremor or muscle rigidity. Japanese researchers have shown that a heart imaging study technique, called MIBG scintigraphy, may be especially useful in the study of psychiatric-onset DLB. Previous research revealed 18 out of 35 subjects with late-onset depression, slowed movements and an abnormal scan developed DLB within 6 years. Further research is needed to confirm and better understand these findings.


The new research criteria for MCI-LB, along with the description of two new possible patterns of how DLB may develop early in the disease course, now allows for a unified global approach to the study of DLB before dementia develops. By assessing study participants with MCI-LB over time, research will provide greater insights on ways to identify the disease at its very earliest stages. This may help identify different subtypes in how the disease presents and progresses. Ultimately, the study of MCI-LB will contribute data and biological samples needed for the study of disease-modifying treatments for Lewy body dementias.

Reference: McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020:94(7);1-13