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
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