History of falls in Parkinson disease is associated with reduced cholinergic activity

Bohnen, Nicolaas I.; Müller, Martijn; Koeppe, Robert A.; Studenski, Stephanie A.; Kilbourn, Michael; Frey, Kirk A.; Albin, Roger L.

doi:10.1212/wnl.0b013e3181c1ded6

Cited by 350 publications

(260 citation statements)

References 31 publications

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“…Thalamic cholinergic changes are also described in PD without dementia and are associated with a propensity for falls (Bohnen et al, 2009). Although there were no significant differences in the parkinsonian motor scores between the two subgroups of low versus normal range thalamic acetylcholinesterase activity, the subgroup with lower thalamic acetylcholinesterase activity had a greater proportion of patients with a history of falls compared with the normal range subgroup.…”

Section: Heterogeneity Of Cholinergic Denervation In Pd and Clinical mentioning

confidence: 83%

“…Furthermore, acetylcholinesterase activity may be a less robust marker of cerebellar cholinergic nerve terminals because cerebellar vesicular acetylcholine transporter levels are low in this region. Consequently, motor correlates of cholinergic denervation in these structures cannot be excluded by our [ 11 C]methyl-4-piperidinyl propionate PET study (Bohnen et al, 2009;Gilman et al, 2010).…”

Section: Mixed Cholinergic and Dopaminergic Correlates Of Cognitive Pmentioning

confidence: 96%

“…In addition to the well-known reductions in dopaminergic pathways, there is also evidence for alterations in cholinergic pathways in PD (Arendt et al, 1983). Previous studies found cognitive correlates of cortical cholinergic denervation (Bohnen et al, 2006b;Shimada et al, 2009), whereas subcortical (pontine tegmentum projection system) denervation is associated with a history of falls and gait problems in PD (Bohnen et al, 2009;Gilman et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

Bohnen

Müller

Kotagal

et al. 2012

J Cereb Blood Flow Metab

162

173

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Parkinson's disease (PD) is a multisystem neurodegenerative disorder. Heterogeneous clinical features may reflect heterogeneous changes in different brain regions. In contrast to the pronounced nigrostriatal denervation characteristic of PD, cholinergic changes are less marked. We investigated cholinergic innervation activity in PD subjects relative to normal subjects. Nondemented PD subjects (n = 101, age 65.3±7.2 years) and normal subjects (n = 29, age 66.8 ± 10.9 years) underwent clinical assessment and [ 11 C]methyl-4-piperidinyl propionate acetylcholinesterase and [ 11 C]dihydrotetrabenazine monoaminergic positron emission tomography (PET) imaging. Cholinergic projection changes were heterogeneous for 65 out of 101 PD subjects who had neocortical and thalamic acetylcholinesterase activity within the normal range. The remainder had combined neocortical and thalamic (13/101), isolated neocortical (18/101), or isolated thalamic (5/101) acetylcholinesterase activity below the normal range. The low neocortical acetylcholinesterase activity subgroup had significantly lower global cognitive performance compared with the normal range subgroup (F = 7.64, P = 0.0069) with an independent effect for nigrostriatal denervation (F = 7.60, P = 0.0074). The low thalamic acetylcholinesterase activity subgroup did not differ from the normal thalamic acetylcholinesterase activity subgroup in cognitive performance or motor impairments except for a history of falls (P = 0.0023). Cholinergic denervation is heterogeneous with reduced neocortical and/or thalamic acetylcholinesterase activity in 36% of nondemented PD subjects with corresponding clinical phenotypic variation. Results also show independent cognitive effects for both cholinergic and dopaminergic system changes in nondemented PD subjects.

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Section: Heterogeneity Of Cholinergic Denervation In Pd and Clinical mentioning

confidence: 83%

Section: Mixed Cholinergic and Dopaminergic Correlates Of Cognitive Pmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

Bohnen

Müller

Kotagal

et al. 2012

J Cereb Blood Flow Metab

162

173

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show abstract

“…Recent evidence suggests that a history of falls is associated with cholinergic deficits in the thalamus, presumably reflecting the loss of innervation from the pedunculopontine nucleus, and does not correlate with striatal DA innervation [103].…”

Section: Motor Complicationsmentioning

confidence: 99%

Neuroimaging in Parkinson's Disease

Stoessl

2011

Neurotherapeutics

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“…However, differences in AChE activity between early and advanced PD patients were nonsignificant, suggesting that cholinergic dysfunction occurs early, but does not progress with the disease (Shimada et al, 2009). Cortical and thalamic cholinergic denervation as measured by [ 11 C]PMP PET were associated with increased falls, slower gait speed, and increased freezing of gait in PD patients, suggesting that cholinergic degeneration is a major factor leading to impaired postural control and gait dysfunction in PD (Bohnen et al, 2014(Bohnen et al, , 2013(Bohnen et al, , 2009.…”

Section: Cholinergic Systemmentioning

confidence: 99%

Imaging in Parkinson's Disease

Politis

Pagano

Niccolini

2017

International Review of Neurobiology

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History of falls in Parkinson disease is associated with reduced cholinergic activity

Abstract: Objective: To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD).Background: There is a need to explore nondopaminergic mechanisms of gait control as the major-

Cited by 350 publications

References 31 publications

Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

Neuroimaging in Parkinson's Disease

Imaging in Parkinson's Disease

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