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Mesopontine cholinergic neuron involvement in Lewy body dementia and multiple system atrophy

From the Departments of Neurology (A.M.S., L.C.B., P.A.L., B.W.B., P.S., E.E.B.) and Anatomic Pathology (J.E.P.), Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Dr Benarroch, Mayo Clinic, Department of Neurology, 811 Guggenheim Building, 200 First Street SW, Rochester, MN 55905 benarroch.eduardo{at}mayo.edu.

Background: The pedunculopontine (PPT) and laterodorsal (LDT) tegmental nuclei are involved in control of REM sleep and thalamocortical arousal. REM sleep behavior disorder (RBD) is a feature of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), which is also associated with visual hallucinations and cognitive fluctuations. We sought to determine the degree of PPT/LDT involvement in DLB compared to MSA.

Methods: We counted the cholinergic neurons in the PPT and LDT in 13 patients with neuropathologically confirmed DLB, 11 patients with MSA, and 11 control cases. Five patients with DLB and eight patients with MSA had history or polysomnographic evidence of RBD. Ten patients with DLB and no patient with MSA had history of visual hallucinations or cognitive fluctuations.

Results: There was a significant loss of PPT and LDT neurons in both DLB and MSA. Cell loss in both the PPT and LDT was more severe in MSA than in DLB. The number of cells/section for the PPT were 148 ± 21 in controls, 54 ± 10 in DLB (p < 0.001), and 20 ± 3 in MSA (p < 0.001), and for the LDT, 112 ± 16 in controls, 49 ± 8 in DLB (p < 0.01), and 16 ± 2 in MSA (p < 0.001). Severity of neuronal loss in MSA or DLB did not relate to the presence or absence of history of RBD.

Conclusions: Loss of cholinergic pedunculopontine tegmental nuclei/laterodorsal tegmental nuclei neurons occurs in both dementia with Lewy bodies and multiple system atrophy but is probably not the primary mechanism of REM sleep behavior disorder in these disorders.

Abbreviations: AAA = abdominal aortic aneurysm; CAD = coronary artery disease; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disorder; DD = disease duration; DLB = dementia with Lewy bodies; GI = gastrointestinal; LDT = laterodorsal tegmental nucleus; MSA = multiple system atrophy; NB = neurogenic bladder; OH = orthostatic hypotension; OPCA = olivopontocerebellar atrophy; PMD = postmortem delay; PPT = pedunculopontine tegmental nucleus; PSG = polysomnography; PSP = progressive supranuclear palsy; RBD = REM sleep behavior disorder; SND = striatonigral degeneration.

Disclosure: The authors report no conflicts of interest.

Received June 27, 2007. Accepted in final form August 8, 2007.