Quantitative electroencephalogram utility in predicting conversion of mild cognitive impairment to dementia with Lewy bodies.
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ABSTRACT:
SUBMITTER: Bonanni L
PROVIDER: S-EPMC4270449 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo predict the risk of probable dementia with Lewy bodies (DLB) competing with Alzheimer disease (AD) dementia by hippocampal volume (HV) in patients with mild cognitive impairment (MCI) with impairments in amnestic or nonamnestic cognitive domains.MethodsPatients with MCI (n = 160) from the Mayo Clinic Alzheimer's Disease Research Center, who participated in an MRI study at baseline from 2005 to 2014, were followed with approximately annual clinical evaluations. HVs were analyzed from 3T MRIs using FreeSurfer (5.3). Hippocampal atrophy was determined from the most normal 10th percentile of the measurement distributions in a separate cohort of clinically diagnosed patients with AD dementia. The subdistribution hazard ratios for progression to probable DLB and AD dementia were estimated by taking into account the competing risks.ResultsDuring a median (range) follow-up of 2.0 (0.7-8.1) years, 20 (13%) patients with MCI progressed to probable DLB, and 61 (38%) progressed to AD dementia. The estimated subdistribution hazard ratio (95% confidence interval) for normal HV relative to hippocampal atrophy for progression to AD dementia was 0.56 (0.34-0.91; p = 0.02) after taking into account the competing risks. The estimated hazard ratio for normal HV relative to hippocampal atrophy for progression to probable DLB was 4.22 (1.42-12.6; p = 0.01) after adjusting for age and after including the MCI subtype in the model.ConclusionsPreserved hippocampal volumes are associated with increased risk of probable DLB competing with AD dementia in patients with MCI. Preservation of HV may support prodromal DLB over AD, particularly in patients with MCI with nonamnestic features.
| S-EPMC5135023 | biostudies-literature
Project description:Previous resting-state fMRI studies in dementia with Lewy bodies have described changes in functional connectivity in networks related to cognition, motor function, and attention as well as alterations in connectivity dynamics. However, whether these changes occur early in the course of the disease and are already evident at the stage of mild cognitive impairment is not clear. We studied resting-state fMRI data from 31 patients with mild cognitive impairment with Lewy bodies compared to 28 patients with mild cognitive impairment due to Alzheimer's disease and 24 age-matched controls. We compared the groups with respect to within- and between-network functional connectivity. Additionally, we applied two different approaches to study dynamic functional connectivity (sliding-window analysis and leading eigenvector dynamic analysis). We did not find any significant changes in the mild cognitive impairment groups compared to controls and no differences between the two mild cognitive impairment groups, using static as well as dynamic connectivity measures. While patients with mild cognitive impairment with Lewy bodies already show clear functional abnormalities on EEG measures, the fMRI analyses presented here do not appear to be sensitive enough to detect such early and subtle changes in brain function in these patients.
| S-EPMC8563567 | biostudies-literature
Project description:Background and purposeAn early and accurate diagnosis of Dementia with Lewy bodies (DLB) is critical because treatments and prognosis of DLB are different from Alzheimer's disease (AD). This study was carried out in Japan to validate an Electroencephalography (EEG)-derived machine learning algorithm for discriminating DLB from AD which developed based on a database of EEG records from two different European countries.MethodsIn a prospective multicenter study, patients with probable DLB or with probable AD were enrolled in a 1:1 ratio. A continuous EEG segment of 150 seconds was recorded, and the EEG data was processed using MC-004, the EEG-based machine learning algorithm, with all clinical information blinded except for age and gender.ResultsEighteen patients with probable DLB and 21 patients with probable AD were the included for the analysis. The performance of MC-004 differentiating probable DLB from probable AD was 72.2% (95% CI 46.5-90.3%) for sensitivity, 85.7% (63.7-97.0%) for specificity, and 79.5% (63.5-90.7%) for accuracy. When limiting to subjects taking ≤5 mg donepezil, the sensitivity was 83.3% (95% CI 51.6-97.9), the specificity 89.5% (66.9-98.7), and the accuracy 87.1% (70.2-96.4).ConclusionsMC-004, the EEG-based machine learning algorithm, was able to discriminate between DLB and AD with fairly high accuracy. MC-004 is a promising biomarker for DLB, and has the potential to improve the detection of DLB in a diagnostic process.
| S-EPMC8970386 | biostudies-literature
Project description:The clinical course of dementia with Lewy bodies patients is heterogeneous. The ability to more accurately prognosticate survival is important.The objective of this study was to investigate hippocampal volume as a predictor of survival in dementia with Lewy bodies patients.Survival analysis for time from onset of cognitive symptoms to death was carried out using Cox proportional hazards models. Given their age and total intracranial volume, patients were dichotomized into low/medium (0%-66.7%) and high (66. 7%-100%) hippocampal volume categories. The models using these categories to predict survival were adjusted for field strength, APOE ?4 status, and estimated onset age of cognitive problems.We investigated 167 consecutive patients with dementia with Lewy bodies. The median age at MRI was 72 years (interquartile range 67-76), and 80% were male. The median time from estimated first cognitive symptom to death was 7.4 years (interquartile range:5.7-10.2). Lower hippocampal volumes were significantly associated with higher risk of death (hazard ratio 1.28; 95% confidence interval 1.04-1.58; P?=?.024). The predicted median survival for participants with onset of cognitive symptoms at age 68 was 10.63 years (95% confidence interval 8.66-14.54) for APOE ?4 negative, high hippocampal volume participants; 8.89 years (95% confidence interval 7.56-12.36) for APOE ?4 positive, high hippocampal volume participants; 8.10 years (95% confidence interval 7.34-11.08) for APOE ?4 negative, low/medium hippocampal volume participants; and 7.38 (95% confidence interval 6.74-9.29) years for APOE ?4 positive, low/medium hippocampal volume participants.Among patients with clinically diagnosed dementia with Lewy bodies, those with neuroimaging evidence of hippocampal atrophy have shorter survival times. © 2016 International Parkinson and Movement Disorder Society.
| S-EPMC4931944 | biostudies-literature
Project description:BackgroundBlood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.MethodsPlasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.ResultsProbable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).ConclusionMarkers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.
| S-EPMC10755229 | biostudies-literature
Project description: Not available
| S-EPMC8985413 | 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: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
Project description:Gut microbiota and fecal bile acids were analyzed in 278 patients with α-synucleinopathies, which were comprised of 28 patients with dementia with Lewy bodies (DLB), 224 patients with Parkinson's disease (PD), and 26 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Similarly to PD, short-chain fatty acids-producing genera were decreased in DLB. Additionally, Ruminococcus torques and Collinsella were increased in DLB, which were not changed in PD. Random forest models to differentiate DLB and PD showed that high Ruminococcus torques and high Collinsella, which presumably increase intestinal permeability, as well as low Bifidobacterium, which are also observed in Alzheimer's disease, were predictive of DLB. As Ruminococcus torques and Collinsella are also major secondary bile acids-producing bacteria, we quantified fecal bile acids and found that the production of ursodeoxycholic acid (UDCA) was high in DLB. Increased UDCA in DLB may mitigate neuroinflammation at the substantia nigra, whereas neuroinflammation may not be critical at the neocortex. Theraeutic intervention to increase Bifidobacteirum and its metabolites may retard the development and progression of DLB.
| S-EPMC9734655 | biostudies-literature