Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease

Walker, Zuzana; Costa, Durval C.; Walker, R. W. H.; Lee, Lean; Livingston, Gill; Jaros, Evelyn; Perry, Robert H.; McKeith, Ian G.; Katona, Cornelius

doi:10.1212/01.wnl.0000123248.39847.1d

Cited by 138 publications

(102 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, in theory this association could be different in DLB patients. It seems that there is a difference in the predilection of DAT SPECT tracer uptake in the basal ganglia between PD and DLB patients, with DLB patients showing a significantly lower caudate nucleus-toputamen ratio (9,14). Thus, basal ganglia pathology might, after all, differ between DLB and PD patients-results that are supported by Walker et al (9).…”

Section: Discussionmentioning

confidence: 83%

“…We identified only one DAT SPECT imaging study including 15 DLB patients correlating DAT binding (in which 123 I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl)nortropane [ 123 I-FP-CIT] was used as the radioligand) with parkinsonism. The authors suggested that there might be a difference in the predilection for DAT uptake in PD versus DLB, since the caudate-to-putamen ratio was less reduced in DLB than in PD and, further, no correlation between severity of parkinsonism and DAT binding was found in DLB patients (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

et al. 2013

View full text Add to dashboard Cite

Patients who have dementia with Lewy bodies (DLB) show both clinical and histopathologic overlap with Alzheimer disease patients and Parkinson disease patients. In this study, we correlated the core features of DLB (dementia, parkinsonism, hallucinations, and fluctuations) with striatal dopamine transporter (DAT) availability as assessed with SPECT and 123 I-N-(3-iodoprop-2E-enyl)-2-b-carbomethoxy-3b-(4-methylphenyl) nortropane ( 123 I-PE2I) in patients with newly diagnosed DLB. Methods: Two hundred eighty-eight patients were consecutively included in the study as they were referred for diagnostic SPECT scanning of DAT with 123 I-PE2I. Of those patients, 51 had, on the basis of clinical guideline criteria, a probable-DLB diagnosis at follow-up 16 6 11.6 mo later. Before or on the day of the SPECT scan, DLB patients had a routine neurologic examination including Hoehn and Yahr grading and were cognitively evaluated with the Mini Mental State Examination. The central feature in dementia with Lewy bodies (DLB) is progressive dementia, but compared with other forms of dementia it has several additional frequent core features, namely fluctuations, hallucinations, and parkinsonism. Parkinson disease (PD), DLB, and PD dementia are seen as a spectrum of the same condition, "Lewy body diseases" (1). In the clinic, DLB and PD dementia are nosologically differentiated only by the time span between the development of parkinsonism and dementia. In DLB, cognitive problems occur less than a year after the onset of parkinsonism (2). The dopamine system is deeply involved in all Lewy body diseases, and dopamine is reduced in the basal ganglia as a consequence of the aggregation of Lewy bodies in this area of the brain (3,4).Imaging of the dopamine transporter (DAT) with SPECT serves as a surrogate marker of the nerve connection between axons from the substantia nigra and neurons in the striatum (5,6). An in vitro study of brains from monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, meant as a model of human DLB, suggested that the loss of DAT and the loss of striatal dopamine content are linearly correlated (7).In PD, many studies have shown a clear correlation between DAT binding and core features of parkinsonism (8). We identified only one DAT SPECT imaging study including 15 DLB patients correlating DAT binding (in which 123 I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl)nortropane [ 123 I-FP-CIT] was used as the radioligand) with parkinsonism. The authors suggested that there might be a difference in the predilection for DAT uptake in PD versus DLB, since the caudate-to-putamen ratio was less reduced in DLB than in PD and, further, no correlation between severity of parkinsonism and DAT binding was found in DLB patients (9).SPECT imaging of cerebral blood flow has demonstrated frontoparietooccipital hypoperfusion patterns in DLB patients (10). The frontal hypoperfusion is interesting, since the dorsolateral circuit involved in planning and attention connects the frontal cortex with the striatum and ...

show abstract

Section: Discussionmentioning

confidence: 83%

mentioning

confidence: 99%

Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In vivo striatum dopaminergic denervation with loss of presynaptic striatal dopamine transporter (DAT), as measured by single-photon emission tomography (SPECT) and PET, is a consistent finding among patients with probable DLB, compared to clinically normal controls and patients with Alzheimer's disease dementia (Walker et al, 2002(Walker et al, , 2004O'Brien et al, 2004;McKeith et al, 2007). 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).…”

Section: Discussionmentioning

confidence: 96%

“…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

View full text Add to dashboard Cite

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 =

show abstract

“…2) (Walker et al, 2002;Donnemiller et al, 1997;O´Brien et al, 2004) and postsynaptic receptors (Walker et al, 1997) has been shown in SB, unlike in AD. Moreover, Walker et al (2004) found a consistent, non-asymmetrical decrease in uptake between caudate and putamen, an observation that could also differentiate this condition from PD. …”

Section: Dementia With Lewy Bodies (Dlb)mentioning

confidence: 58%

123-I ioflupane (Datscan®) presynaptic nigrostriatal imaging in patients with movement disorders

Castrejón¹,

Vicente²,

Romera³

et al. 2005

Braz. arch. biol. technol.

View full text Add to dashboard Cite

123-I Ioflupane (Datscan®) presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123-I Ioflupane SPECT is able to distinguish between Parkinson's disease (PD) and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neurodegenerative disordersinvolving the substantia nigra.

show abstract

Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease

Abstract: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Cited by 138 publications

References 19 publications

Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

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

123-I ioflupane (Datscan®) presynaptic nigrostriatal imaging in patients with movement disorders

Contact Info

Product

Resources

About