LBD Patients Research Articles

Diagnostic performance RT‐QuIC based detection of alpha‐synuclein seeds in a clinical cohort with cognitive impairment

AbstractBackgroundLewy Body Dementia (LBD) is the second most common neurodegenerative dementia. To date, no validated biochemical marker is available to support clinical diagnosis. The development of the Real‐Time Quaking‐Induced Conversion (RT‐QuIC) assay for detecting alpha‐synuclein (aSyn) seeds in biological samples can be a sensitive biomarker specific for the diagnosis easily applicable in a clinical setting. We aimed to describe the diagnostic performance of RT‐QuIC aSyn assay in cerebrospinal fluid (CSF) to diagnose LBD in a clinical cohort with cognitive impairment.MethodA cohort of subjects with cognitive impairment (neurodegenerative and non‐neurodegenerative) with available CSF sample at the moment of first evaluation was selected by convenience sample in our database. Subjects had clinical follow‐ups ranging from 6 months to 12 years and current clinical diagnosis according to established consensus criteria. The diagnostic performance of RT‐QuIC aSyn for the diagnosis of LBD were evaluated.ResultThe test was evaluated in 155 subjects (age 65 years (SD 11), MMSE 24 (SD 4.5), 56% male) with the following clinical diagnoses: LBD (n = 40), Alzheimer’s disease (AD) (n = 73)(all with compatible CSF profile), frontotemporal dementia (FTD) (n = 7), non‐neurodegenerative mild cognitive impairment (MCI) (n = 21), other neurodegenerative diagnoses (n = 12) and healthy controls (n = 2). aSyn was detected in 33/40 (83%) LBD patients, 7/73 (10%) AD, 0/7 FTD patients, 0/21 MCI patients, 0/12 patients with other neurodegenerative diseases and 0/2 healthy controls.Only 3/7 (42%) LBD subjects with a negative RT‐QuIC asyn fulfilled criteria for LBD (established or prodromal) at the moment of first evaluation as compared with 23/33 (69%) of LBD with positive RTQuIC suggesting a more initial disease in the negative group at the moment of CSF sampling.The sensitivity and specificity of the assay were 83% and 94% respectively for the diagnosis of LBD, with a PPV of 83% and a NPV of 94%.ConclusionDetection of αSyn seeds by RT‐QuIC has a good performance in identifying patients with LBD in a clinical cohort of cognitively impaired subjects. The test also identifies aSyn co‐pathology in a subgroup of subjects diagnosed with AD.

T1 MRI reveals differential hippocampal atrophy in Lewy Body Disorders with and without Alzheimer’s copathology

AbstractBackgroundLewy body disorders (LBD) include Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB). LBD are the second leading cause of neurodegenerative dementia after Alzheimer’s disease (AD). An estimated 50% of LBD patients have coexisting AD pathology (LBD+AD), which correlates with shorter time to dementia and death. Autopsy evidence suggests that verbal memory impairment correlates with the severity of hippocampal tau pathology in LBD. However, it is unknown whether greater hippocampal tau burden in LBD+AD causes neurodegeneration detectable by in vivo structural MRI, and whether hippocampal atrophy explains verbal memory impairment.MethodUsing a case‐control design, we studied 87 patients with clinical diagnoses of LBD (PD, n = 52; PDD, n = 12; DLB, n = 23) with available T1 MRI and AD biomarkers or, and cognitively‐normal controls (n = 131). AD copathology was defined hierarchically by: a) AD “intermediate” or “high” by ABC neuropathologic criteria; 2) positive amyloid PET; and 3) CSF total tau:β‐amyloid1‐42 ratio > 0.3 (autopsy‐validated cutpoint). The Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was applied to subjects’ T1 MRIs. Hippocampal volume (HV) was compared between controls, LBD‐AD, and LBD+AD, and correlated with verbal memory scores. Linear regression was used to test the association of AD copathology (independent variable) and HV (dependent variable), covarying for age, sex, education, and clinical diagnosis.ResultStatistically significant differences (ANOVA p = 0.002) in bilateral HV (expressed as percentage of intracranial volume) were seen between groups (mean 0.456for controls, 0.444±0.045 for LBD‐AD, and 0.416±0.063 for LBD+AD). Tukey’s test showed significant differences between LBD+AD vs controls (p = 0.001) and LBD+AD vs. LBD‐AD (p = 0.047). Linear regression showed statistically significant association of LBD+AD with bilateral HV (p = 0.034). Among all LBD patients, hippocampal volume positively correlated with verbal memory (immediate recall: r2 = 0.24, p = 0.033, delayed recall: r2 = 0.22, p = 0.042, recognition discrimination r2 = 0.58, p<0.001).ConclusionIn patients with LBD, AD copathology is associated with increased hippocampal atrophy as measured by in vivo T1 MRI, which correlates with greater verbal memory deficits. This work supports the that AD copathology impairs cognition in LBD via hippocampal neurodegeneration.

Using plasma ptau181 in Lewy Body Disease spectrum for the identification of Alzheimer’s disease co‐pathology

AbstractBackgroundLewy body disease (LBD) patients frequently present with Alzheimer’s disease (AD) co‐pathology, which influences disease progression, cognitive decline, and brain atrophy. AD‐related pathology can be identified with new blood‐based biomarkers like plasma phosphorylated‐tau181 (ptau181).We aimed to determine whether plasma ptau181 helps identify AD‐related co‐pathology in LBD, and whether plasma ptau181 is associated with clinical features, and AD cerebrospinal (CSF) biomarkers.MethodFrom a total of 632 Stanford research participants, we selected 245: 115 cognitively normal (CN), 47 Parkinson’s disease (PD) with normal cognition, 47 on the LBD spectrum (31 MCI and 16 dementia), and 36 on the AD spectrum (14 MCI and 22 dementia). Plasma ptau181 levels were measured with Lumipulse G fully automated platform by Fujirebio with Lumipulse G Assays. A subset of the participants had available AD CSF biomarkers (N = 201) and/or 18F‐Florbetaben PET imaging (N = 73). Diagnostic accuracy was evaluated with area‐under‐the‐curve (AUC) values from receiver‐operating characteristic (ROC) analyses. Linear regression models adjusted for confounding factors were used to analyze effects of baseline plasma ptau181 levels on global cognition (MoCA), global function (CDR‐SOB), motor function (UPDRS Part III), and functional disability (Hoehn and Yahr).ResultPlasma ptau181 levels were higher in the LBD spectrum group compared to CN and PD with normal cognition groups, but lower than in the AD spectrum group.Plasma ptau181 levels predicted CSF ptau181/Aβ42 ratio in LBD spectrum patients with an AUC = 0.87. Including age, sex, years of education, and APOE E4 genotype levels improved the prediction of the model (AUC = 0.94).In the LBD spectrum group, males and females showed similar plasma ptau181 levels, and we found no association between plasma ptau181 levels with age, sex, years of education, MoCA, CDR‐SOB, UPDRS Part III, or Hoehn and Yahr. Nevertheless, plasma ptau181 levels were associated with CSF ptau181 levels and amyloid‐β42/40 after controlling for age and sex.ConclusionPlasma ptau181 levels help identify LBD patients with AD co‐pathology, and are associated with AD CSF biomarkers. These findings support the use of plasma ptau181 as a screening tool for AD co‐pathology in patients with LBD and cognitive impairment.

Proof-of-concept for characterization of neurodegenerative disorders utilizing two non-REM sleep biomarkers.

This proof-of-concept study aimed to determine whether the combined features of two non-rapid eye movement (NREM) sleep biomarkers acquired predominantly in-home could characterize different neurodegenerative disorders. Sleep spindle duration and non-REM hypertonia (NRH) were evaluated in seven groups including a control group (CG = 61), and participants with isolated REM sleep behavior disorder (iRBD = 19), mild cognitive impairment (MCI = 41), Parkinson disease (PD = 16), Alzheimer disease dementia (ADem = 29), dementia with Lewy Bodies or Parkinson disease dementia (LBD = 19) and progressive supranuclear palsy (PSP = 13). One-way analysis of variance (ANOVA), Mann-Whitney U, intra-class (ICC) and Spearman ranked correlations, Bland-Altman plots and Kappa scores, Chi-square and Fisher exact probability test, and multiple-logistic regression were focused primarily on spindle duration and NRH and the frequencies assigned to the four normal/abnormal spindle duration/NRH combinations. ANOVA identified group differences in age, sleep efficiency, REM, NRH (p < 0.0001) and sleep time (p = 0.015), Spindle duration and NRH each demonstrated good night-to-night reliabilities (ICC = 0.95 and 0.75, Kappa = 0.93 and 0.66, respectively) and together exhibited an association in the PD and LBD groups only (p < 0.01). Abnormal spindle duration was greater in records of PSP (85%) and LBD (84%) patients compared to CG, MCI, PD and ADem (p < 0.025). Abnormal NRH was greater in PSP = 92%, LBD = 79%, and iRBD = 74% compared to MCI = 32%, ADem = 17%, and CG = 16% (p < 0.005).The combination biomarker normal spindle duration/normal NRH was observed most frequently in CG (56%) and MCI (41%). ADem most frequently demonstrated normal spindle duration/normal NRH (45%) and abnormal spindle duration/normal NRH (38%). Normal spindle duration/abnormal NRH was greatest in iRBD = 47%, while abnormal spindle duration/abnormal NRH was predominant in PSP = 85% and LBD = 74%. The NREM sleep biomarkers spindle duration and NRH may be useful in distinguishing patients with different neurodegenerative disorders. Larger prospective cohort studies are needed to determine whether spindle duration and NRH can be combined for prodromal assessment and/or monitoring disease progression.

Visual mental imagery in Lewy Body Dementia patients with visual hallucinations: preliminary results

AbstractBackgroundLewy body dementia (LBD) is characterized by the presence of visual hallucinations (VH), however mechanisms underpinning these phenomena are still unknown. Visual mental imagery (VMI) is defined as the ability to see with the mind’s eye, in the absence of adequate sensory input (Kosslyn, 1987). Hallucinations are defined as percepts in the absence of an appropriate stimulus from the external world. Both visual mental images and VH consist of a “stimulus‐independent” image production, however the association between VH and VMI has not yet been investigated in LBD. The aim of the study was to investigate VMI processes in patients LBD with VH.MethodNineteen LBD patients (mean age = 75.4, SD = 6.9; mean education = 10.2, SD = 4) attending the “Sapienza” University Hospital in Rome and 13 Healthy controls (HC) (mean age = 71.9,DS = 7.9; mean education = 12.8, SD = 4.9) matched for age and education were enrolled. VMI was assessed in patients and HC by means of an adapted version of The Complete Visual Mental Imagery Battery (CVMIB; Palermo et al., 2016), including tasks probing the generation of different visual mental images (i.e. object; building and face), maintenance, inspection and transformation processes, and through the O’Clock test (Grossi et al.,1994) including a perceptual and imaginative tasks.ResultNon‐parametric analyses revealed that LBD performed worse than HC in all CVMIB tasks. Furthermore LBD performed worse than HC in both O’clock tests, imaginative and perceptual ones, suggesting a role of the visuoperceptual deficits in VMI alterations. It is worth noting LBD and HC did not differ in response time.ConclusionLBD patients with VH show alterations of VMI compared to HC. Alterations of VMI process might influence VH occurrence. Thus, it is possible that VH and VMI share neural mechanisms and are placed on a continuum along the perceptual processes. Future studies are needed to disentangle the possible role of perceptual difficulties in VMI alterations in LBD and to clarify how VMI alterations are related to VH occurrence. Furthermore, investigating VMI and its relationship with visuoperceptual skills in LBD patients could help to better characterize their neuropsychological profile.

MINDFULNESS AND CAREGIVING EXPERIENCE IN ADRD CAREGIVERS

Abstract Mindfulness (being present in the moment without judgement) has been linked to greater caregiver emotional health. Recent mindfulness-based interventions report improved coping skills, mood, and reduced stress in dementia caregivers. In this cross-sectional study of 141 ADRD caregivers, we assessed whether the relationship between caregiver mindfulness and caregiver experience varies by caregiver gender, relationship to patient (spouse-vs-child), etiology (AD-vs-LBD), or stage (MCI-vs-dementia). A stratified univariate analytic approach was used. Four mindfulness parameters (AMPS scale) were used: global score (GS), decentering (F1), positive (F2), and negative emotional regulation (F3). Outcomes included positive and negative appraisals of caregiving (PANAC), preparedness, care confidence, and depression. GS was linked to positive outcomes in male (rPANAC+=0.32/p=0.005), spouse caregivers (rPANAC+)=0.32/p=0.006 ) of ADRD patients regardless of etiology (rPANAC+=0.31/p=0.013 for AD; rconfidence=0.31/p=0.036 for LBD) and stage (rPANAC+=0.33/p=0.010 and rpreparedness=0.38,/p=0.008 for MCI; rPANAC+=0.29/p=0.011 and rconfidence=0.31/p=0.007 for dementia). Inverse relationships were observed with negative outcomes in male (rPANAC-=-0.46/p=0.002 and rdepression=-0.41/p=0.005), spouse caregivers (rPANAC-=-0.25/p=0.035 and rdepression=-0.30/p=0.009) of AD patients (rPANAC-=-0.25/p=0.043 and rdepression=-0.33/p=0.009) in early stages (rdepression=-0.41/p=0.001). F2 contributed to most relationships, with F3 and F1 significant in some but not all caregiver groups. Specifically, male spouse caregivers of AD patients regardless of stage may benefit from full-scope (F1-F3) programs while those of LBD patients from programs focused on improving emotional regulation (F2-F3). Wives of AD and LBD patients may in turn benefit from programs to improve positive emotional regulation (F2). Findings suggest that tailoring mindfulness-based interventions to specific caregiver groups may be effective in improving caregiver experience and mood.

Specific Cerebrospinal Fluid SerpinA1 Isoform Pattern in Alzheimer's Disease.

SerpinA1 (α1-antitrypsin) is a soluble glycoprotein, the cerebrospinal fluid (CSF) isoforms of which showed disease-specific changes in neurodegenerative disorders that are still unexplored in Alz-heimer’s disease (AD). By means of capillary isoelectric focusing immunoassay, we investigated six serpinA1 isoforms in CSF samples of controls (n = 29), AD-MCI (n = 29), AD-dem (n = 26) and Lewy body disease (LBD, n = 59) patients and correlated the findings with CSF AD core biomarkers (Aβ42/40 ratio, p-tau, t-tau). Four CSF serpinA1 isoforms were differently expressed in AD patients compared to controls and LBD patients, especially isoforms 2 and 4. AD-specific changes were found since the MCI stage and significantly correlated with decreased Aβ42/40 (p < 0.05) and in-creased p-tau and t-tau levels in CSF (p < 0.001). Analysis of serpinA1 isoform provided good di-agnostic accuracy in discriminating AD patients versus controls (AUC = 0.80) and versus LBD patients (AUC = 0.92), with best results in patients in the dementia stage (AUC = 0.97). SerpinA1 isoform expression is altered in AD patients, suggesting a common, albeit disease-specific, in-volvement of serpinA1 in most neurodegenerative disorders.

A simple Mini‐Mental State Exam subscale formula to help differentiate Alzheimer's disease from dementia with Lewy bodies

AbstractBackgroundAlthough there are clinical criteria for the diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), the two conditions may sometimes be difficult to differentiate. Prior research has documented that the two conditions often have striking neuropsychological differences, and there have been a number of reports promoting the ability of simple screening tests to help the diagnostic accuracy of the clinician. These screening tests, however, have been limited in their specificity. Building upon previous research from our group and others, we now report a simple manipulation of the Mini‐Mental State Exam (MMSE) subscale scores that greatly improves the specificity of the screening test.MethodWe studied all AD and DLB patients who visited our dementia clinic during an 18‐month period, including both new and follow‐up visit patients. All who had an MMSE administered to them were included. All MMSE scores were included. The first MMSE recorded for each patient was studied.ResultWe studied the MMSEs from 136 AD and 24 DLB patients. The mean patient age was 77.8 ± 11.1 for AD, 78.3 ± 8.7 for DLB. Mean MMSE score was 20.0 ± 6.0 for AD, 21.8 ± 5.1 for DLB; MMSE range 1‐30 for AD, 10‐28 for DLB. Many different formulae were studied using the MMSE subscales of Memory (3 points max), Attention (5 points max), and Pentagon‐copying (1 point max) to determine which was the best to differentiate AD from DLB. The simple formula of the Pentagon score minus the Memory score (P‐M, range 1 to ‐3) provided the best discrimination between the AD and DLB patient groups. For P‐M scores = 1, the specificity of the equation to identify AD was 0.92. For P‐M scores &lt; 0, the specificity to identify DLB was 0.85. The sensitivities for the P‐M equation were 0.43 for AD (scores = 1) and 0.46 for DLB (scores &lt; 0).ConclusionThe simple MMSE subscale formula of Pentagon score minus Memory score (P‐M) provided good specificities to identify AD patients (0.92) and LBD patients (0.85) within our cohort of AD and DLB patients. A weakness of the P‐M equation was relatively weak sensitivity.

Correlation of frontal atrophy and CSF tau levels with neuropsychiatric symptoms in patients with cognitive impairment: A memory clinic experience

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy.MethodOne‐hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Lewy‐body disease, LBD; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T‐MRI and/or CT and CSF. Cortical atrophy was assessed with medial temporal atrophy (MTA), posterior atrophy (PA) and global cortical atrophy‐frontal lobe (GCA‐F) scales. BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium.ResultDelusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p&lt;0.05, p&lt;0.001, and p&lt;0.05), with LBD patients showing higher scores for hallucinations (vs MCI, p&lt;0.001, and AD, p&lt;0.05) and psychosis cluster (vs MCI, p&lt;0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p&lt;0.01), while a positive non‐significant relationship was observed in MCI. Higher GCA‐F scores were associated with delusions and apathy (p&lt;0.05, on both hemispheres) and to hallucinations (left: p&lt;0.01, right: p&lt;0.05). GCA‐F scores were positively correlated with psychosis cluster (right: p&lt;0.05), and agitation/aggression (left: p&lt;0.05). Conversely, nighttime disturbances were positively correlated with both GCA‐F and MTA scores (left: p&lt;0.01; right: p&lt;0.05).ConclusionOur results suggest that psychotic symptoms are significantly more represented in LBD patients, and that CSF tau and frontal atrophy are associated with the occurrence and severity of BPSD in clinical practice. Longitudinal studies are however required to ascertain their actual predictive value.

Abnormal event‐related EEG theta responses in patients with dementia with Lewy bodies and Parkinson's disease dementia

AbstractBackgroundParkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by intracellular Lewy bodies in the brain neurons and clinical symptoms including cognitive impairment and flucations, motor symptoms, and hallucinations with some differences, namely non‐motor symptoms appear earlier in DLB over PDD patients (McKeith et al., 2017). An unmet need in the actual diagnostic criteria is the availability of biomarkers probing working brain cognitive systems. A promising biomarker may be derived from the frequency analysis of electroencephalographic oscillatory responses (EROs) during cognitive demands, as a decrease of frontal‐central EROs at theta (4‐7 Hz) frequencies was reapatedly demonstrated in Alzheimer’s disease patients with mild cognitive impairment and dementia over cognitively unimpaired (CU) persons (Yener et al., 2007; Guntekin et al., 2008). In this line, the present study tested the hypothesis of abnormal event‐related EROs at theta frequencies in PDD and DLB patients.MethodElectroencephalographic activity was recorded during a visual oddball paradigm (i.e., 30% of target stimuli requiring mental counting intermingled with 70% of stimuli to be ignored) in 15 PDD, 12 DLB, and 15 CU persons. EROs at theta power and phase‐locking were computed for the oddball target stimuli and compared among the groups (ANOVA, p &lt; 0.05).ResultAs compared to the CU group, both PDD and DLB groups showed a strong topographically widespread reduction in ERO theta power (p &lt; 0.005) (Figure 1). They also showed a strong reduction in ERO theta phase‐locking, especially in frontal‐central locations (p &lt; 0.0001)( Figure 2).ConclusionThe present study showed that ERO theta power and phase‐locking during a standard visual oddball paradigm probing visual focused attention and short‐term memory may be suitable biomarkers to investigate working cognitive brain systems in both PDD and LBD patients.

Frontal lobe dysfunction is associated with reduced DAT-SPECT accumulation in Lewy body disease

IntroductionLewy body disease (LBD) causes olfactory or cognitive dysfunction even before motor symptoms emerge. Recent reports indicate that the dopamine transporter (DAT), which can be imaged using single-photon emission computed tomography (123I-ioflupane SPECT), is related to olfactory and cognitive dysfunction in LBD patients. We suspected that decreased cerebral blood flow (CBF) in the frontal lobe might be involved in these relationships. If so, then the results of these examinations may be useful in assessing the pathological progression of Lewy bodies. MethodsWe retrospectively analyzed the data of 139 de novo consecutive patients with LBD. We used the Odor Stick Identification Test for Japanese (OSIT-J) and the Frontal Assessment Battery (FAB) to evaluate olfactory and frontal lobe dysfunction, respectively. Among the 139 patients, ultimately 84 patients were analyzed and underwent 123I-ioflupane SPECT within 3 months (before or after) of the OSIT-J and FAB. We categorized patients on the basis of whether frontal lobe CBF was reduced (n = 28) or normal (n = 56). ResultsThe average OSIT-J and FAB scores were 4.0 and 14.1, respectively, and the scores on the two tests were significantly correlated. Furthermore, OSIT-J scores were significantly correlated with the specific binding ratio (SBR) in both groups. The SBR was correlated with FAB scores in patients with reduced CBF in the frontal lobe, but not in those with normal CBF. ConclusionFrontal lobe dysfunction and striatum dysfunction are correlated in LBD patients only after CBF has declined. Also, there is a time lag in the appearance of olfactory dysfunction and frontal lobe dysfunction in LBD patients. As with pathological development, olfaction is impaired earliest, followed by striatal, and then frontal lobe dysfunction.

Correlation of Frontal Atrophy and CSF Tau Levels With Neuropsychiatric Symptoms in Patients With Cognitive Impairment: A Memory Clinic Experience

Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy.Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease, AD; Lewy-body disease, LBD; frontotemporal dementia, FTD; vascular dementia, VD) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed with medial temporal atrophy (MTA), posterior atrophy (PA), and global cortical atrophy-frontal lobe (GCA-F) scales. BPSD were rated using the Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium.Results: Delusions, hallucinations, and psychosis cluster were differently distributed among the diagnostic groups (p < 0.05, p < 0.001, and p < 0.05), with LBD patients showing higher scores for hallucinations (vs. MCI, p < 0.001, and AD, p < 0.05) and psychosis cluster (vs. MCI, p < 0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p = 0.08), confirmed by beta regression (p < 0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p < 0.05, on both hemispheres) and hallucinations (left: p < 0.01, right: p < 0.05). GCA-F scores were positively correlated with psychosis cluster (right: p < 0.05), and agitation/aggression (left: p < 0.05). Conversely, nighttime disturbances were positively correlated with both GCA-F and MTA scores (left: p < 0.01; right: p < 0.05).Conclusion: Our results suggest that psychotic symptoms are significantly more represented in LBD patients and that CSF tau and frontal atrophy are associated with the occurrence and severity of BPSD in clinical practice. Longitudinal studies are however required to ascertain their actual predictive value.

Is This Within Reach? Left but Not Right Brain Damage Affects Affordance Judgment Tendencies.

The ability to judge accurately whether or not an action can be accomplished successfully is critical for selecting appropriate response options that enable adaptive behaviors. Such affordance judgments are thought to rely on the perceived fit between environmental properties and knowledge of one's current physical capabilities. Little, however, is currently known about the ability of individuals to judge their own affordances following a stroke, or about the underlying neural mechanisms involved. To address these issues, we employed a signal detection approach to investigate the impact of left or right hemisphere injuries on judgments of whether a visual object was located within reach while remaining still (i.e., reachability). Regarding perceptual sensitivity and accuracy in judging reachability, there were no significant group differences between healthy controls (N = 29), right brain damaged (RBD, N = 17) and left brain damaged stroke patients (LBD, N = 17). However, while healthy controls and RBD patients demonstrated a negative response criterion and thus overestimated their reach capability, LBD patients' average response criterion converged to zero, indicating no judgment tendency. Critically, the LBD group's judgment tendency pattern is consistent with previous findings in this same sample on an affordance judgment task that required estimating whether the hand can fit through apertures (Randerath et al., 2018). Lesion analysis suggests that this loss of judgment tendency may be associated with damage to the left insula, the left parietal and middle temporal lobe. Based on these results, we propose that damage to the left ventro-dorsal stream disrupts the retrieval and processing of a stable criterion, leading to stronger reliance on intact on-line body-perceptive processes computed within the preserved bilateral dorsal network.

Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson’s and Lewy body diseases

AbstractBackgroundParkinson’s disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also by cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients having visual hallucinations.MethodClinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer’s disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched for cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources.ResultAs a confirmation of previous studies, compared to the Nold subjects, the AD, LBD, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the LBD and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As novel results, in relation to the LBD and PD patients without visual hallucinations and the control groups (Nold, AD), those with visual hallucinations were characterized by higher parietal delta source activities (LBD, Figure 1) and parieto‐occipital alpha sources activities (PD, Figure 2).ConclusionThese novel results suggest that in LBD and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies in parietal cortex are differently related to visual hallucinations despite the essence of alpha‐synucleinopathy.

Recognition of musical emotions and their perceived intensity after unilateral brain damage

For the hemispheric laterality of emotion processing in the brain, two competing hypotheses are currently still debated. The first hypothesis suggests a greater involvement of the right hemisphere in emotion perception whereas the second hypothesis suggests different involvements of each hemisphere as a function of the valence of the emotion. These hypotheses are based on findings for facial and prosodic emotion perception. Investigating emotion perception for other stimuli, such as music, should provide further insight and potentially help to disentangle between these two hypotheses. The present study investigated musical emotion perception in patients with unilateral right brain damage (RBD, n = 16) or left brain damage (LBD, n = 16), as well as in matched healthy comparison participants (n = 28). The experimental task required explicit recognition of musical emotions as well as ratings on the perceived intensity of the emotion. Compared to matched comparison participants, musical emotion recognition was impaired only in LBD participants, suggesting a potential specificity of the left hemisphere for explicit emotion recognition in musical material. In contrast, intensity ratings of musical emotions revealed that RBD patients underestimated the intensity of negative emotions compared to positive emotions, while LBD patients and comparisons did not show this pattern. To control for a potential generalized emotion deficit for other types of stimuli, we also tested facial emotion recognition in the same patients and their matched healthy comparisons. This revealed that emotion recognition after brain damage might depend on the stimulus category or modality used. These results are in line with the hypothesis of a deficit of emotion perception depending on lesion laterality and valence in brain-damaged participants. The present findings provide critical information to disentangle the currently debated competing hypotheses and thus allow for a better characterization of the involvement of each hemisphere for explicit emotion recognition and their perceived intensity.

EEG alpha reactivity and cholinergic system integrity in Lewy body dementia and Alzheimer\u2019s disease

BackgroundLewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is characterised by marked deficits within the cholinergic system which are more severe than in Alzheimer’s disease (AD) and are mainly caused by degeneration of the nucleus basalis of Meynert (NBM) whose widespread cholinergic projections provide the main source of cortical cholinergic innervation. EEG alpha reactivity, which refers to the reduction in alpha power over occipital electrodes upon opening the eyes, has been suggested as a potential marker of cholinergic system integrity.MethodsEyes-open and eyes-closed resting state EEG data were recorded from 41 LBD patients (including 24 patients with DLB and 17 with PDD), 21 patients with AD, and 40 age-matched healthy controls. Alpha reactivity was calculated as the relative reduction in alpha power over occipital electrodes when opening the eyes. Structural MRI data were used to assess volumetric changes within the NBM using a probabilistic anatomical map.ResultsAlpha reactivity was reduced in AD and LBD patients compared to controls with a significantly greater reduction in LBD compared to AD. Reduced alpha reactivity was associated with smaller volumes of the NBM across all groups (ρ = 0.42, pFDR = 0.0001) and in the PDD group specifically (ρ = 0.66, pFDR = 0.01).ConclusionsWe demonstrate that LBD patients show an impairment in alpha reactivity upon opening the eyes which distinguishes this form of dementia from AD. Furthermore, our results suggest that reduced alpha reactivity might be related to a loss of cholinergic drive from the NBM, specifically in PDD.

The effects of repetitive neck-muscle vibration on postural disturbances after a chronic stroke

ObjectiveWe aimed to test a repeated program of vibration sessions of the neck muscles (rNMV) on postural disturbances and spatial perception in patients with right (RBD) versus left (LBD) vascular brain damage. MethodsThirty-two chronic stroke patients (mean age 60.9±10 yrs and mean time since stroke 4.9±4 yrs), 16 RBD and 16 LBD, underwent a program of 10 sessions of NMV over two weeks. Posturography parameters (weight-bearing asymmetry (WBA), Xm, Ym, and surface), balance rating (Berg Balance Scale (BBS), Timed Up and Go (TUG)), space representation (subjective straight ahead (SSA), longitudinal body axis (LBA), subjective visual vertical (SVV)), and post-stroke deficiencies (motricity index, sensitivity, and spasticity) were tested and the data analyzed by ANOVA or a linear rank-based model, depending on whether the data were normally distributed, with lesion side and time factor (D-15, D0, D15, D21, D45). ResultsThe ANOVA revealed a significant interaction between lesion side and time for WBA (P<0.0001) with a significant shift towards the paretic lower limb in the RBD patients only (P=0.0001), whereas there was no effect in the LBD patients (P=0.98). Neither group showed a significant modification of spatial representation. Nonetheless, there was a significant improvement in motricity (P=0.02), TUG (P=0.0005), and BBS (P<0.0001) in both groups at the end of treatment and afterwards. ConclusionsrNMV appeared to correct WBA in RBD patients only. This suggests that rNMV could be effective in treating sustainable imbalance due to spatial cognition disorders.

Representational drawing following brain injury.

Research has shown that damage to either the left or right hemisphere can lead to deficits in visuoconstructional skills including drawing and figure copying. Nevertheless, research would suggest that the nature of the deficits arising from left and right brain injury are distinct in nature if not severity, with the right hemisphere, and parietal cortex specifically, seen as critical for obtaining accurate spatial relations and the left hemisphere important for effective organisation (i.e., executive function). Much of this work on drawing and figure copying following brain damage has rested on qualitative assessments or crude marking scales with descriptive anchors for what constitutes good or poor performance. We employed quantitative analyses of drawings developed to assess accuracy in novice and expert artists. We analyzed drawings of a cube and a star in 50 patients (23, left brain damaged: LBD; 27 right brain damaged: RBD) who had suffered strokes. Our analysis was sensitive to the presence of neglect on the cube (i.e., missing left sided details) with voxel-wise lesion symptom mapping (VLSM) highlighting involvement of expected brain regions (superior temporal and supramarginal gyri). With left-sided omissions removed from analyses, we failed to find any difference between LBD and RBD patients. While the presence of left neglect appeared to exaggerate errors, this was only significant for errors of scale and proportion for the star drawing. VLSM of the distinct error domains demonstrated white matter involvement (and a minor contribution from the right insula) with respect to scale errors of the cube only. Finally, blinded judgements of hemisphere of lesion based on qualitative assessment of the drawings were no better than chance. These results suggest that figure copying is a complex task relying on large scale neural networks involving both hemispheres. Clearly, models of visuoconstructional capacity that emphasise right hemisphere dominance are not entirely accurate.

Structural correlates of attention dysfunction in Lewy body dementia and Alzheimer\u2019s disease: an ex-Gaussian analysis

BackgroundLewy body dementia (LBD) and Alzheimer’s disease (AD) are common forms of degenerative dementia. While they are characterized by different clinical profiles, attentional deficits are a common feature. The objective of this study was to investigate how attentional problems in LBD and AD differentially affect different aspects of reaction time performance and to identify possible structural neural correlates.MethodsWe studied reaction time data from an attention task comparing 39 LBD patients, 28 AD patients, and 22 age-matched healthy controls. Data were fitted to an ex-Gaussian model to characterize different facets of the reaction time distribution (mean reaction time, reaction time variability, and the subset of extremely slow responses). Correlations between ex-Gaussian parameters and grey and white matter volume were assessed by voxel-based morphometry.ResultsBoth dementia groups showed an increase in extremely slow responses. While there was no difference between AD and controls with respect to mean reaction time and variability, both were significantly increased in LBD patients compared to controls and AD. There were widespread correlations between mean reaction time and variability and grey matter loss in AD, but not in LBD.ConclusionsThis study shows that different aspects of reaction time performance are differentially affected by AD and LBD, with a difference in structural neural correlates underlying the observed behavioural deficits. While impaired attentional performance is linked to brain atrophy in AD, in LBD it might be related to functional or microstructural rather than macrostructural changes.

Updating impairments and the failure to explore new hypotheses following right brain damage

We have shown recently that damage to the right hemisphere impairs the ability to update mental models when evidence suggests an old model is no longer appropriate. We argue that this deficit is generic in the sense that it crosses multiple cognitive and perceptual domains. Here, we examined the nature of this updating impairment to determine more precisely the underlying mechanisms. We had right (RBD, N = 12) and left brain damaged (LBD, N = 10) patients perform versions of our picture-morphing task in which pictures gradually morph from one object (e.g., shark) to another (e.g., plane). Performance was contrasted against two groups of healthy older controls, one matched on age (HCO-age-matched, N = 9) and another matched on general level of cognitive ability (HCO-cognitively-matched, N = 9). We replicated our earlier findings showing that RBD patients took longer than LBD patients and HCOs to report seeing the second object in a sequence of morphing images. The groups did not differ when exposed to a morphing sequence a second time, or when responding to ambiguous images outside the morphing context. This indicates that RBD patients have little difficulty alternating between known representations or labeling ambiguous images. Instead, the difficulty lies in generating alternate hypotheses for ambiguous information. Lesion overlay analyses, although speculative given the sample size, are consistent with our fMRI work in healthy individuals in implicating the anterior insular cortex as critical for updating mental models.