Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo

Klein, Johannes; Eggers, Carsten; Kalbe, Elke; Weisenbach, Simon; Hohmann, Carina; Vollmar, Stefan; Baudrexel, Simon; Diederich, Nico J.; Heiss, Wolf‐Dieter; Hilker, Rüdiger

doi:10.1212/wnl.0b013e3181d55f61

Cited by 308 publications

(263 citation statements)

References 41 publications

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“…Corticopetal dopaminergic pathways mainly project to the frontal cortex. In PD, reduced dopaminergic and cholinergic transmission has been demonstrated in a pattern coinciding well with the frontal and posterior clusters demonstrated in the present work 42. As such, the present findings in the PD group could, hypothetically, be construed as an effect of reduced dopaminergic (the frontal cluster) and reduced cholinergic transmission (the posterior cluster) in accordance with the dual syndrome hypothesis.…”

Section: Discussionsupporting

confidence: 90%

Impaired synaptic function is linked to cognition in Parkinson's disease

Selnes

Stav

Johansen

et al. 2017

Ann Clin Transl Neurol

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ObjectiveCognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐β, and presynaptic deposits of α‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐β, and the synapse related‐markers CSF neurogranin and α‐synuclein.MethodsThirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years).ResultsAll subjects had CSF amyloid‐β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, α‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐β and α‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group.Interpretation CSF Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease.

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Section: Discussionsupporting

confidence: 90%

Impaired synaptic function is linked to cognition in Parkinson's disease

Selnes

Stav

Johansen

et al. 2017

Ann Clin Transl Neurol

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“…DLB and PDD are associated with severe cholinergic deafferentiation of the neocortex, especially in parietooccipital regions. This is congruent with 18 F-FDG PET findings of posterior hypometabolism in dementia (37).…”

Section: Pd and Cognitive Impairmentsupporting

confidence: 86%

Metabolic Imaging in Parkinson Disease

et al. 2016

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This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed.

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“…While the dopaminergic degeneration has been widely documented to affect the striatum of patients with DLB (Walker et al, 2004;Klein et al, 2010), a cholinergic network alteration involving the striatum has been postulated in the Lewy body disease spectrum of disorders (Langlais et al, 1993) but its mechanism is still poorly understood (Bohnen and Albin, 2011). In this setting, our finding of an association between higher PiB retention and higher atrophy rates in the caudate and putamen nuclei suggest an accelerated subcortical neuronal injury involving the global PiB SUVR (x-axes) and regional grey matter annualized log Jacobian (y-axes) in patients with DLB, after adjusting for age.…”

Section: Discussionmentioning

confidence: 99%

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Sarro¹,

Senjem

Lundt

et al. 2016

Brain

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Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-b deposition as measured with 11 C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-b deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-b deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline 11 C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent 11 C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on threedimensional T 1 -weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline 11 C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline 11 C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P 5 0.05). Greater baseline 11 C-Pittsburgh compound B standard unit value ratio was also associated with greater ventricular expansion rates (P 5 0.01) and greater worsening over time in Clinical Dementia Rating Scale, sum of boxes (P = 0.02). In conclusion, in patients with probable dementia with Lewy bodies, higher amyloid-b deposition at baseline is predictive of faster neurodegeneration in the cortex and also in the striatum. This distribution is suggestive of possible interactions among amyloid-b, tau and a-synuclein aggregates, which needs further investigation. Furthermore, higher amyloid-b deposition at baseline predicts a faster clinical decline over time in patients with probable dementia with Lewy bodies. Keywords: DLB; structural MRI; beta-amyloid; amyloid imaging; brain atrophy Abbreviations: AChEI = acetylcholinesterase inhibitor; CDR-SOB = Clinical Dementia Rating scale, Sum of Boxes; DLB = dementia with Lewy bodies; MMSE = Mini-Mental State Examination; PiB = 11 C-Pittsburgh compound B; SUVR = standardized uptake value ratio; TBM-SyN = tensor-based morphometry using symmetric diffeomorphic image normalization; UPDRS-III =

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Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo

Cited by 308 publications

References 41 publications

Impaired synaptic function is linked to cognition in Parkinson's disease

Impaired synaptic function is linked to cognition in Parkinson's disease

Metabolic Imaging in Parkinson Disease

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

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