Sleep Disorder Highly Predictive of Common Dementia Type

Caroline Cassels

March 20, 2013

San Diego, California — Rapid eye movement (REM) sleep behavior disorder (RBD) is the strongest predictor of determining risk of developing dementia with Lewy bodies (DLB) in men, new research suggests.

A study conducted by investigators at the Mayo Clinic in Jacksonville, Florida, showed such patients are about 5 times more likely to have DLB, the second most common form of dementia, if they experience RBD compared with 1 of the other "core" risk factors currently used to make the diagnosis, which include parkinsonism, fluctuating cognition, or hallucinations.

"The findings strongly suggest that DLB should be added to the list of core features for dementia with Lewy bodies," study investigator Melissa Murray, PhD, from the Mayo Clinic in Jacksonville, Florida, told Medscape Medical News.

The study was presented here at the American Academy of Neurology (AAN) 65th Annual Meeting.

Most Cases Male

Characterized by a loss of muscle atonia that occurs during normal sleep, patients with RBD are able to move during REM while sleeping and "act out" their dreams, which are often vivid and unpleasant, said Dr. Murray.

This can result in violent episodes in which patients can kick and punch during REM sleep, resulting in harm to themselves and/or their bed partners.

Dr. Melissa Murray

Dr. Murray also noted that RBD can present 3 or more decades before a diagnosis of LBD is made and that up to 80% of individuals with the disorder are men.

In the latest consensus guidelines on the clinical and pathologic diagnosis of DLB, which were published in 2005, RBD is classified as a "suggestive feature" of LBD.

However, Dr. Murray noted, a growing body of research suggests RBD warrants consideration as a key feature.

Stronger Predictor Than Current Criteria

The aim of the current study was to determine quantitative differences in cortical atrophy and hippocampal abnormality in autopsy-confirmed DLB in patients with and without probable RBD.

The investigators also wanted to examine whether hippocampal volume, DLB core features, and RBD together can predict the likelihood of DLB.

The researchers examined MRI brain scans on 75 patients diagnosed with probable DLB.

Using DLB consortium pathology criteria, the researchers identified 75 consecutive low- to high-likelihood autopsy-confirmed DLB cases from the Mayo Clinic AD Research Center. All patients had undergone MRI of the brain before death.

Pathologic burden of hyperphosphorylated neurofibrillary-tau, α-synuclein, and β-amyloid from the hippocampus was quantified. Atlas-based quantification of hippocampal volumes and voxel-based analysis of antemortem MRI examinations were performed.

The results revealed that hippocampal neurofibrillary-tau (P =.007) and β-amyloid (P < .001) burden was lower and hippocampal and parietotemporal cortical volumes larger in those with a history of probable RBD than in those without a history of probable RBD.

The investigators also reported that antemortem MRI and DLB clinical features predicting a higher likelihood of autopsy-confirmed DLB showed a trend for hippocampal volume (odds ratio, 1.13; P = .08) and a history of probable RBD increased the odds (odds ratio, 5.78; P = .004) of predicting pathology associated with DLB likelihood.

Parkinsonism approached significance (P = .10) in a model with hippocampal volume and probable RBD but not fluctuations or visual hallucinations.

Screening Important

In light of the fact that RBD is a stronger predictor of DLB likelihood than the currently established core features, Dr. Murray said she is hopeful that this paper, as well as previous research, will be considered when the diagnostic criteria for DLB are updated.

In the meantime, she said, clinicians need to be aware of RBD and its link to DLB and ask patients and their bed partners about sleep disturbances.

DLB, she noted, is on a spectrum that can range from mild to severe. At its worst, patients can injure themselves or others, and obviously this extreme form may be picked up more easily than mild or moderate cases.

This underlines the need to ask about sleep and pay attention to more "subtle" signs of RBD, which can include flailing of limbs during the night or falling out of bed, said Dr. Murray.

She added that screening for RBD can help in the differential diagnosis of LBD and Alzheimer's disease (AD). She noted that in the Mayo Clinic databases, only 2% to 3% of patients with AD have a history of RBD.

Once LBD is diagnosed, patients can benefit from treatment with cholinesterase inhibitors. Although these agents are not disease modifying, they do benefit patients with LBD and are significantly more effective in this population than in patients with AD.

In addition, RBD itself can be effectively treated with the benzodiazepine clonazepam, either alone or in combination with the supplement melatonin.

Dr. Murray has disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 65th Annual Meeting. Abstract S44.006. Presented March 21, 2012.

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