Lewy Body Versus Alzheimer's Dementias and Parkinson's

One clinical challenge is making an accurate diagnosis in patients with dementia.

Alzheimer's disease is typically the predominant diagnosis in dementia. However a significant number of patients will present with dementia due to Lewy Body disease, Parkinson's dementia,  frontotemporal dementia or vascular dementia.

A recent study helps clinicians to distinguish Lewy Body  from Alzheimer's dementia and Parkinson's disease.

Douglas Scharre and collegues from Ohio State University conducted a matched pair analysis of 21 patients with Lewy Body dementia with 21 patients with Alzheimer's disease and 21 patients with Parkinson's disease.

Parkinson's disease subjects in this study had higher cognitive function scores than the Lewy Body disease subjects but were matched on level of motor impairment.

Subject groups were assessed on a variety of motor, cognitive and neuropsychological domains. Lewy Body dementia subjects differed from the Alzheimer's group in the following areas:

• Higher impairment scores on executive function and visuospatial function
• Lower impairment on memory and orientation
• Higher scores on measures of sleepiness
• Higher scores on fluctuation of cognitive and behavior deficits
• More hallucinations
• More sleep apnea

Lewy body dementia subjects differed from the Parkinson's disease group in the following areas:

• More impairment in axial motor function
• More impairment in gait and balance function
• Higher scores on measures of sleepiness
• Higher scores on fluctuation of cognitive and behavior deficits
• More hallucinations
• More sleep apnea

The authors noted that measures of axial motor, gait and balance impairment correlated higher with level of executive function impairment, visuomotor function impairment and global cognitive impairment.

This is an important study and highlights the need for specific neuropsychological testing along with assessment of motor, gait and balance domains dementia evaluations.

Readers with more interest in this study can access the author's uncorrected proofs by clicking on the DOI link in the citation below.

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Photo of brown thrasher from my back yard is from my files.

Scharre, D., Chang, S., Nagaraja, H., Park, A., Adeli, A., Agrawal, P., Kloos, A., Kegelmeyer, D., Linder, S., Fritz, N., Kostyk, S., & Kataki, M. (2016). Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases Journal of Alzheimer's Disease, 1-10 DOI: 10.3233/JAD-160384

Brain Imaging in Diagnosis of Lewy Body Dementia

Brain image highlighting right insula implicated in DLB

Recent information has emerged concerning the suicide death of the comedian/actor Robin Williams.

Autopsy results have demonstrated that Robin Williams suffered from dementia with Lewy bodies (DLB).

This public case demonstrates the difficulty in making a correct diagnosis of DLB prior to the findings at autopsy.

In a previous post I reported on a screening tool for clinicians that appears to have some promise for screening for high-risk DLB patients.

In this post, I want to follow up on this topic by reviewing a recent brain imaging study that targeted patterns of brain cortical thinning in the dementias.

The key elements in the design of this research study included the following elements:

• Subjects: 28 subjects with prodromal DLB, 27 subjects with prodromal Alzheimer's disease (AD), 31 subjects with DLB, 54 subjects with AD and cognitively normal elderly adults.
• Brain Imaging: Structural magnetic resonance imaging (MRI) with a 3 Tesla scanner
• Statistical Analysis: FreeSurfer analysis of regional cortical thickness pattern across diagnosis groups

The key findings from the study included the following:

• DLB subjects showed distinct patterns of cortical thinning compared to AD
• DLB was associated with increased thinning of the right insular cortex
• AD was associated with left parahippocampal thinning and bilateral parietal lobe thinning
• In those with full dementia, AD subjects demonstrated more thinning in the enterorhinal cortex

The authors of this study note in the discussion section of the paper that the key finding is the finding of right insular cortex thinning in DLB. This finding may allow use of brain imaging as a sensitive addition to the use of clinical and neuropsychological assessment in elderly with early and later dementia.

This study will need to be replicated in additional independent samples. Some research groups may already have scan data that may be able to be analyzed in an attempt to replicate the current study.

Readers with more interest in the study can access the free full-text manuscript by clicking on the PMID link in the citation below.

Image of the right insular cortex is from a screen shot from my iPad using the Brain Tutor app.

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Blanc F, Colloby SJ, Philippi N, de Pétigny X, Jung B, Demuynck C, Phillipps C, Anthony P, Thomas A, Bing F, Lamy J, Martin-Hunyadi C, O'Brien JT, Cretin B, McKeith I, Armspach JP, & Taylor JP (2015). Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages. PloS one, 10 (6) PMID: 26061655

Improving Diagnosis of Lewy Body Dementia

This month I have been focusing on research advances in neuropsychology in neuroscience medicine.

My daily feed screener picked up a report of a screening tool for Lewy Body Dementia (LBD) today.

LBD is often confused with Alzheimer's disease. Distinguishing the two is important for management and selection of appropriate drug treatment.

This research is not published in a free full-text manuscript format but there is a link to the scale for readers with more interest.

The research study examined the validity of a newly developed scale called the Lewy Body Composite Risk Score or LBCRS.

This score is calculated from a ten-item yes-no questionnaire that includes questions on the presence or absence of:

• Movement initiation difficulty
• Muscular rigidity
• Postural instability with frequent falls
• Tremor at rest
• Excessive daytime sleepiness
• Illogical, incoherent thought
• Staring or blank look spells
• Visual hallucinations
• Acting out dreams
• Orthostatic hypotension/autonomic insufficiency

Using a cutoff score of 3 positive responses yielded a high discrimination of LBD from Alzheimer's disease in a group of 256 patients.

The link to the scale and administration directions can be found here.

Accurate tools for identifying LBD are needed and this scale may be helpful for clinicians. It will be interesting to follow to see if this study can be replicated in another sample.

Figure of brain basal ganglia commonly affected in LBD is an iPad screenshot from the app 3D Brain from the author's files.

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Galvin JE (2015). IMPROVING THE CLINICAL DETECTION OF LEWY BODY DEMENTIA WITH THE LEWY BODY COMPOSITE RISK SCORE. Alzheimer's & dementia (Amsterdam, Netherlands), 1 (3), 316-324 PMID: 26405688

Improving Dementia Diagnosis With a Sleep Marker

Dementia presents a growing challenge for clinicians both in the assessment as well as treatment domains.  Autopsy remains the only definitive diagnostic intervention that can confirm Alzheimer's disease and the other forms of senile dementia including vascular dementia, dementia with Lewy bodies, frontotemporal dementia and other dementia variants.

Since autopsy studies do not provide clinicians or their patients any direct benefits during the patient's lifetime, better diagnostic tests and clinical predictors are needed.

A recent study from a team of neurologists, psychiatrists, sleep medicine specialists and pathologists from the Mayo Clinic supports the potential of a sleep disorder to aid in the diagnosis of dementia with Lewy bodies.  Lewy bodies are distinct accumulations of proteins found in the brains of individuals with parkinsonism and Lewy body dementia.  They are identified at autopsy by special stains viewed under a microscope.

Dementia with Lewy bodies is often considered the second most common type of dementia.  The clinical diagnostic criteria were revised in 2005 and include core and suggestive features.  The core features include: fluctuations in cognitive abilities, parkinsonism and visual hallucinations.  The suggestive features include: sensitivity to antipsychotic drugs, reduced brain dopamine uptake on functional brain imaging and presence of the sleep disorder known as REM sleep behavior disorder (RBD).

The 2005 diagnostic guidelines for dementia with Lewy bodies can be made when patients have two of the core criteria or one of the core criteria and at least one suggestive criteria.

REM sleep behavior disorder (RBD) is a sleep disorder characterized by violent (or other dangerous) behavior during the REM or dream or nightmare phase of sleep.  This behavior can include punching, kicking, yelling, jumping out of bed often in response to specific content of the dream that is being experienced.  Individuals with RBD can physically injure themselves or their bed partners with their violent behaviors.

In normal individuals, REM sleep includes temporary muscle paralysis preventing individuals from physically responding to dreams or nightmares.  Loss of this REM sleep paralysis can lead to development of RBD.  RBD is felt to indicate disregulation of several brain neurotransmitter systems including dopamine, serotonin and acetylcholine.  This dysregulation may explain extreme sensitivity of patients with RBD to adverse effects of a variety of psychotropic drugs including antidepressants and antipsychotics.

The Mayo Clinic study included a prospective longitudinal study of a group of patients with dementia who were seen four times per year until their deaths.  Postmortem autopsies were conducted on 234 patients.  Seventy seven (33%) of the sample met pathological criteria for diffuse Lewy body disease.

The authors looked specifically at RBD as a predictor of true diagnosis of dementia with Lewy body disease.  They found that RBD was three times more powerful as a predictor of Lewy body dementia than any of the the core criteria of Lewy body dementia.

This study confirms the value of RBD in diagnosing Lewy body dementia--in fact it supports moving RBD up to a core feature rather than a suggestive feature.  A second multicenter study by Bliwise and colleagues has confirmed the high rates of RBD in Lewy body dementia compared to those with Alzheimer's disease.

These findings should encourage clinicians to aggressively look for RBD in patients with dementia to aid differential diagnosis and the treatment planning in this challenging population.

Photo of typical Santa Fe home architecture taken during sunset in Santa Fe, New Mexico from the author's collection.

Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, Wszolek Z, Graff-Radford NR, Uitti R, Van Gerpen J, Pao W, Knopman D, Pankratz VS, Kantarci K, Boot B, Parisi JE, Dugger BN, Fujishiro H, Petersen RC, & Dickson DW (2011). Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology, 77 (9), 875-82 PMID: 21849645

Bliwise, D., Mercaldo, N., Avidan, A., Boeve, B., Greer, S., & Kukull, W. (2011). Sleep Disturbance in Dementia with Lewy Bodies and Alzheimer’s Disease: A Multicenter Analysis Dementia and Geriatric Cognitive Disorders, 31 (3), 239-246 DOI: 10.1159/000326238