Implication of metabolic and dopamine transporter PET in dementia with Lewy bodies.
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SUBMITTER: Kang SW
PROVIDER: S-EPMC8277897 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nigrostriatal dopaminergic degeneration is a pathological hallmark of dementia with Lewy bodies (DLB). To identify the subregional dopamine transporter (DAT) uptake patterns that improve the diagnostic accuracy of DLB, we analyzed N-(3-[18F] fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) PET in 51 patients with DLB, in 36 patients with mild cognitive impairment with Lewy body (MCI-LB), and in 40 healthy controls (HCs). In addition to a high affinity for DAT, FP-CIT show a modest affinity to serotonin or norepinephrine transporters. Specific binding ratios (SBRs) of the nigrostriatal subregions were transformed to age-adjusted z-scores (zSBR) based on HCs. The diagnostic accuracy of subregional zSBRs were tested using receiver operating characteristic (ROC) curve analyses separately for MCI-LB and DLB versus HCs. Then, the effect of subregional zSBRs on the presence of clinical features and gray matter (GM) density were evaluated in all patients with MCI-LB or DLB as a group. ROC curve analyses showed that the diagnostic accuracy of DLB based on the zSBR of substantia nigra (area under the curve [AUC], 0.90) or those for MCI-LB (AUC, 0.87) were significantly higher than that based on the zSBR of posterior putamen for DLB (AUC, 0.72) or MCI-LB (AUC, 0.65). Lower zSBRs in nigrostriatal regions were associated with visual hallucination, severe parkinsonism, and cognitive dysfunction, while lower zSBR of substantia nigra was associated with widespread GM atrophy in DLB and MCI-LB patients. Taken together, our results suggest that evaluation of nigral DAT uptake may increase the diagnostic accuracy of DLB and MCI-LB than other striatal regions.
| S-EPMC10256694 | biostudies-literature
Project description:Introduction18F-Fluoro-deoxyglucose-positron emission tomography (FDG-PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG-PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis.MethodsFDG-PET scans were visually and semi-quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi-quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features.ResultsAt follow-up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi-quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%).DiscussionFDG-PET is a valuable tool in DLB diagnosis, having visual and semi-quantitative analyses with the highest diagnostic accuracy at ML analyses.
| S-EPMC10746864 | biostudies-literature
Project description:Dementia with Lewy bodies is characterized by α-synuclein accumulation and degeneration of dopaminergic and cholinergic pathways. To gain an overview of brain systems affected by neurodegeneration, we characterized the [18F]FDG-PET metabolic connectivity in 42 dementia with Lewy bodies patients, as compared to 42 healthy controls, using sparse inverse covariance estimation method and graph theory. We performed whole-brain and anatomically driven analyses, targeting cholinergic and dopaminergic pathways, and the α-synuclein spreading. The first revealed substantial alterations in connectivity indexes, brain modularity, and hubs configuration. Namely, decreases in local metabolic connectivity within occipital cortex, thalamus, and cerebellum, and increases within frontal, temporal, parietal, and basal ganglia regions. There were also long-range disconnections among these brain regions, all supporting a disruption of the functional hierarchy characterizing the normal brain. The anatomically driven analysis revealed alterations within brain structures early affected by α-synuclein pathology, supporting Braak's early pathological staging in dementia with Lewy bodies. The dopaminergic striato-cortical pathway was severely affected, as well as the cholinergic networks, with an extensive decrease in connectivity in Ch1-Ch2, Ch5-Ch6 networks, and the lateral Ch4 capsular network significantly towards the occipital cortex. These altered patterns of metabolic connectivity unveil a new in vivo scenario for dementia with Lewy bodies underlying pathology in terms of changes in whole-brain metabolic connectivity, spreading of α-synuclein, and neurotransmission impairment.
| S-EPMC5453453 | biostudies-literature
Project description:PurposeAlpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB.MethodsEighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests.ResultsRegional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R1 was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05.ConclusionThe amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.
| S-EPMC7714680 | biostudies-literature
Project description:Objective: Characteristic parkinsonism is the major comorbidity of dementia with Lewy bodies (DLB). We aimed to differentiate DLB from Alzheimer's disease (AD) with motor dysfunction using a composite scale with a characteristic motor dysfunction questionnaire (MDQ) and dopamine transporter (DAT) imaging. It could help detect DLB easily in healthcare settings without movement disorder specialists. Methods: This is a two-phase study. In the design phase, seven questions were selected and composed of a novel MDQ. In the test phase, all participants with DLB, AD, or non-dementia (ND) control completed dementia and parkinsonism survey, the novel designed questionnaire, DAT imaging, and composite scales of MDQ and DAT. The cutoff scores of the MDQ, semiquantitative analysis of the striatal-background ratio (SBR) and visual rating of DAT, and the composite scale of MDQ and DAT for discriminating DLB from AD or ND were derived and compared. Results: A total of 277 participants were included in this study (126 with DLB, 86 with AD, and 65 with ND). Compared with the AD or ND groups, the DLB group showed a significantly higher frequency in all seven items in the MDQ and a significantly lower SBR. For discrimination of DLB from non-DLB with MDQ, SBR, and composite scale, the cutoff scores of 3/2, 1.37/1.38, and 6/5 were suggested for the diagnosis of DLB with the sensitivities/specificities of 0.91/0.72, 0.91/0.80, and 0.87/0.93, respectively. The composite scale significantly improved the accuracy of discrimination compared with either the MDQ or SBR. Conclusion: This study showed that the novel designed simple questionnaire was a practical screening tool and had similar power to DAT scanning to detect DLB. The questionnaire can be applied in clinical practice and population studies for screening DLB. In addition, the composite scale of MDQ and DAT imaging further improved the diagnostic accuracy, indicating the superiority of the dual-model diagnostic tool.
| S-EPMC8385672 | biostudies-literature
Project description:BackgroundImaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker.ObjectiveTo report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).MethodsThree subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared.ResultsThe clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD.ConclusionPET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.
| S-EPMC10109539 | biostudies-literature
Project description:Dementia with Lewy bodies (DLB) is a clinical diagnosis representing a specific presentation of a pathological α-synucleinopathy (Lewy body disease). DLB is one entity under the broader term Lewy body dementia, which also includes Parkinson's disease dementia. Recent advances in DLB include publication of updated diagnostic criteria and recognition of prodromal DLB states, including mild cognitive impairment, delirium-onset, and psychiatric-onset forms. Research criteria for the mild cognitive impairment form of DLB were published in 2020. Increasing research shows that concomitant Alzheimer's disease pathology in individuals with DLB is common in addition to the α-synucleinopathy pathology. This has implications for biomarker use and expected progression. Identifying biomarkers for DLB is an area of active research. Cerebrospinal fluid and skin biopsy tests are now commercially available in the United States, but their role in routine clinical care is not yet established. Additional research and biomarkers are needed. Research suggests that median survival after DLB diagnosis is 3-4 years, but there are rapidly and slowly progressive forms. Most individuals with DLB die of complications of the disease. Clinical trials for individuals with DLB have increased over the last 5 years, targeting both symptoms and underlying pathology. Effective therapies remain an unmet need, however. This review focuses on recent advances with an emphasis on literature that informs clinical care.
| S-EPMC8613883 | biostudies-literature
Project description:IntroductionMicrobleeds are associated with the development of dementia in older people and are common in Alzheimer's disease (AD). Their prevalence and clinical importance in dementia with Lewy bodies (DLB) is unclear. The objective of this study was to compare the rates of microbleeds in DLB with those in AD and healthy older people, and investigate associations between microbleeds and amyloid deposition, vascular risk and disease severity in DLB.MethodsDLB (n = 30), AD (n = 18) and control (n = 20) participants underwent clinical assessment at baseline and 1 year in this longitudinal observational study. 3T MRI (including T2* susceptibility weighted imaging) and florbetapir PET were carried out at baseline. Microbleeds were rated visually and a standardised uptake value ratio (SUVR) was calculated from florbetapir PET scans.Results40% of DLB subjects had microbleeds compared with 50% of AD and 15% of controls. Compared to DLB without microbleeds, those with microbleeds had higher systolic BP (156 ± 26 v. 135 ± 19 mmHg; p = 0.03), but did not have greater levels of vascular disease or amyloid deposition (SUVR 1.25 ± 0.24 v. 1.25 ± 0.22; p = 0.33). There was evidence of less severe dementia in DLB participants with microbleeds, but these differences may have been driven by a shorter disease duration in those with microbleeds.ConclusionThe presence of microbleeds in DLB is associated with higher blood pressure, but not with other measures of vascular disease or amyloid deposition. The relationship between microbleeds and clinical presentation remains unclear.
| S-EPMC7184053 | biostudies-literature
Project description:Highlights • Dementia with Lewy bodies is associated with a unique metabolic brain network.• Individual patient expression levels for this network correlate with measures of cognitive dysfunction and survival.• The topography of this network differs from that associated with cognitive impairment in PD patients.• Expression levels for this network can help differentiate between the two most common dementia disorders. Purpose Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia, that shares clinical and metabolic similarities with both Alzheimer’s and Parkinson’s disease. In this study we aimed to identify a DLB-related pattern (DLBRP), study its relationship with other metabolic brain patterns and explore its diagnostic and prognostic value. Methods A cohort of 79 participants with DLB, 63 with dementia due to Alzheimer’s disease (AD) and 41 normal controls (NCs) and their 2-[18F]FDG PET scans were analysed for identification and validation of DLBRP. Voxel-wise correlation and multiple linear regression were used to study the relation between DLBRP and Alzheimer’s disease-related pattern (ADRP), Parkinson’s disease-related pattern (PDRP) and PD-related cognitive pattern (PDCP). Diagnostic and prognostic value of DLBRP and of modified DLBRP after accounting for ADRP overlap (DLBRP ⊥ ADRP), were explored. Results The newly identified DLBRP shared topographic similarities with ADRP (R2 = 24%) and PDRP (R2 = 37%), but not with PDCP. We could accurately discriminate between DLB and NC (AUC = 0.99) based on DLBRP expression, and between DLB and AD (AUC = 0.87) based on DLBRP ⊥ ADRP expression. DLBRP expression correlated with cognitive impairment, but the correlation was lost after accounting for ADRP overlap. DLBRP and DLBRP ⊥ ADRP correlated with patients’ survival time. Conclusion DLBRP has proven to be a specific metabolic brain biomarker of DLB, sharing similarities with ADRP and PDRP, but not PDCP. We observed a similar metabolic mechanism underlying cognitive impairment in DLB and AD. DLB-specific metabolic changes were more detrimental for overall survival.
| S-EPMC9207351 | biostudies-literature
Project description:IntroductionThe leucine-rich repeat kinase 2 (LRRK2) gene contains several variants that cause Parkinson's disease (PD) and others that modify PD risk. However, little is known about the role of LRRK2 in dementia with Lewy bodies (DLB). Aims of this study were to screen DLB patients for pathogenic LRRK2 variants and to evaluate associations between common LRRK2 variants and risk of DLB.Methods417 clinical DLB patients and 1790 controls were included in the primary analysis. Additionally, 355 Lewy body disease patients assessed as having a high likelihood of clinical DLB based on neuropathological findings were included in secondary analysis. Seven pathogenic LRRK2 variants were assessed in patients, while 17 common LRRK2 exonic variants and 1 GWAS-nominated common LRRK2 PD-risk variant were evaluated for association with DLB.ResultsWe identified carriers of 2 different pathogenic LRRK2 variants. One clinical DLB patient was a p.G2019S carrier, while in the pathological high likelihood DLB series there was one carrier of the p.R1441C mutation. However, examination of clinical records revealed the p.R1441C carrier to have PD with dementia. Evaluation of common variants did not reveal any associations with DLB risk after multiple testing adjustment. However, a non-significant trend similar to that previously reported for PD was observed for the protective p.N551K-R1398H-K1423K haplotype in the clinical DLB series (OR: 0.76, P = 0.061).ConclusionLRRK2 does not appear to play a major role in DLB, however further study of p.G2019S and the p.N551K-R1398H-K1423K haplotype is warranted to better understand their involvement in determining DLB risk.
| S-EPMC5048558 | biostudies-literature